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Sample records for mite infected lung

  1. Intensity of parasitic mite infection decreases with hibernation duration of the host snail.

    PubMed

    Haeussler, E M; Pizá, J; Schmera, D; Baur, B

    2012-07-01

    Temperature can be a limiting factor on parasite development. Riccardoella limacum, a haematophagous mite, lives in the mantle cavity of helicid land snails. The prevalence of infection by R. limacum in populations of the land snail Arianta arbustorum is highly variable (0-78%) in Switzerland. However, parasitic mites do not occur in host populations at altitudes of 1290 m or higher. It has been hypothesized that the host's hibernation period might be too long at high elevations for mites and their eggs to survive. To test this hypothesis, we experimentally infected snails and allowed them to hibernate at 4°C for periods of 4-7 months. Winter survival of host snails was negatively affected by R. limacum. The intensity of mite infection decreased with increasing hibernation duration. Another experiment with shorter recording intervals revealed that mites do not leave the host when it buries in the soil at the beginning of hibernation. The number of mites decreased after 24 days of hibernation, whereas the number of eggs attached to the lung tissue remained constant throughout hibernation. Thus, R. limacum survives the winter in the egg stage in the host. Low temperature at high altitudes may limit the occurrence of R. limacum.

  2. Disseminated mite infection with ocular involvement in a juvenile bald eagle (Haliaeetus leucocephalus).

    PubMed

    Bueno-Padilla, Irene; Klauss, Gia; Gardiner, Chris H; Wuenschmann, Arno

    2012-07-01

    A bald eagle (Haliaeetus leucocephalus) was found unable to fly and was admitted to The Raptor Center (TRC). Major clinical signs were thin body condition and a cardiac arrhythmia. Ten days after admission to TRC, ophthalmic examination revealed multiple, distinct serpiginous lesions of chorioretinal atrophy in the ocular fundus of the right eye (OD). The bird was euthanized because of clinical deterioration and poor prognosis. Mites of an undetermined species were found histologically in the retina, episcleral tissues, lungs, and liver at the postmortem examination. Disseminated mite infection should be considered in the differential diagnosis of serpiginous chorioretinal lesions in bald eagles (H. leucocephalus).

  3. Disseminated mite infection with ocular involvement in a juvenile bald eagle (Haliaeetus leucocephalus).

    PubMed

    Bueno-Padilla, Irene; Klauss, Gia; Gardiner, Chris H; Wuenschmann, Arno

    2012-07-01

    A bald eagle (Haliaeetus leucocephalus) was found unable to fly and was admitted to The Raptor Center (TRC). Major clinical signs were thin body condition and a cardiac arrhythmia. Ten days after admission to TRC, ophthalmic examination revealed multiple, distinct serpiginous lesions of chorioretinal atrophy in the ocular fundus of the right eye (OD). The bird was euthanized because of clinical deterioration and poor prognosis. Mites of an undetermined species were found histologically in the retina, episcleral tissues, lungs, and liver at the postmortem examination. Disseminated mite infection should be considered in the differential diagnosis of serpiginous chorioretinal lesions in bald eagles (H. leucocephalus). PMID:22151197

  4. Experimental infection of dogs with the nasal mite Pneumonyssoides caninum.

    PubMed

    Gunnarsson, L; Zakrisson, G; Lilliehook, I; Christensson, D; Rehbinder, C; Uggla, A

    1998-06-15

    A successful experimental transmission of the canine nasal mite, Pneumonyssoides caninum, is described. Some 11 weeks after repeated systemic ivermectin treatment, four Beagles were inoculated via the right nostril with 20 P. caninum mites of different sexes and life stages, obtained at the necropsy of an infected dog. The inoculated dogs and a matching uninoculated control were observed for clinical signs for 14 weeks and then euthanised. Vague upper respiratory signs and a transient minor increase in the number of eosinophils in peripheral blood were recorded in the inoculated dogs. At necropsy 4-12 P. caninum mites were found in the nasal cavities and sinuses of the inoculated dogs, but none in the control. In three out of the four infected dogs mites were found in both the right and left nasal cavities and sinuses of the skull. Since in no case more mites than the number used for inoculation were detected it is not clear if the mites managed to reproduce in the dogs. Inflammatory lesions were seen most consistently in the olfactory mucosa, respiratory mucosa and tonsils, and growth of opportunistic bacteria was observed in the tonsils of the infected dogs. The inflammatory lesions seen in the olfactory mucosa may explain why dogs infected with P. caninum sometimes appear to suffer from impaired scenting ability.

  5. Clinical efficacy of milbemycin oxime in the treatment of nasal mite infection in dogs.

    PubMed

    Gunnarsson, L K; Möller, L C; Einarsson, A M; Zakrisson, G; Hagman, B G; Christensson, D A; Uggla, A H; Hedhammar, A A

    1999-01-01

    A multicentric clinical trial was done to evaluate the clinical efficacy of milbemycin oxime in the treatment of nasal mite (Pneumonyssoides caninum) infection in dogs. Milbemycin oxime was given to 70 dogs of different breeds, genders, and ages, with clinical signs associated with nasal mite infection. Twenty-five dogs had a verified infection, and 45 dogs had signs suggestive of nasal mite infection. Milbemycin oxime was given at the dosage of 0.5 to 1.0 mg/kg body weight orally once a week for three consecutive weeks. One month after initiation of treatment, 68 of the dogs had no more clinical signs associated with nasal mite infection.

  6. ST. LOUIS ENCEPHALITIS : TRANSMISSION OF VIRUS TO CHICKENS BY INFECTED MITES DERMANYSSUS GALLINAE AND RESULTING VIREMIA AS SOURCE OF VIRUS FOR INFECTION OF MITES.

    PubMed

    Smith, M G; Blattner, R J; Heys, F M

    1947-08-31

    Transmission of the virus of St. Louis encephalitis to normal chickens by the bite of infected mites (Dermanyssus gallinae) has been demonstrated. Both experimentally infected and naturally infected mites were shown to be capable of transferring the virus of St. Louis encephalitis to chickens by bite. Virus is present in the blood of such chickens in small amounts, so that demonstration of viremia was possible only by utilizing chorioallantoic passage in hens' eggs. However, there is sufficient virus present in the blood for uninfected chicken mites to acquire the virus by feeding on chickens in which viremia has resulted from previous bite of infected mites. Thus it has been shown that the arachnid vector Dermanyssus gallinae is capable of transmitting the virus of St. Louis encephalitis to normal chickens by bite and that such chickens can serve as a source of virus for uninfected mites.

  7. Use of milbemycin oxime in the treatment of dogs with nasal mite (Pneumonyssoides caninum) infection.

    PubMed

    Bredal, W; Vollset, I

    1998-03-01

    Clinical diagnosis of canine nasal mite (Pneumonyssoides caninum) infection is difficult due to the mite's location in the caudal nasal cavity and frontal sinuses. The current study was performed to evaluate the efficacy of milbemycin oxime in treating dogs with nasal mite infection. A prospective open uncontrolled study included 20 dogs with case histories indicating possible nasal mite infection. Inclusion criteria consisted of either nasal mites being demonstrated (group 1, four dogs), or suspicious clinical signs with no other apparent causes, combined with eosinophilia (group 2, 16 dogs). Milbemycin oxime 1 mg/kg was given orally three times at 10-day intervals. In 17 (85 per cent) dogs, clinical signs resolved completely following milbemycin therapy; within 10 days of the first treatment in 13 cases (group 1, four dogs; group 2, nine dogs) and within 14 days in four cases. In the remaining three dogs clinical signs persisted but were diminished.

  8. Experimental infection of Salmonella Enteritidis by the poultry red mite, Dermanyssus gallinae.

    PubMed

    Valiente Moro, C; Chauve, C; Zenner, L

    2007-05-31

    Dermanyssus gallinae is an important ectoparasite of laying hens in Europe and it is suspected of being a vector of pathogens. We carried out an in vitro study to evaluate the role of D. gallinae as a vector of Salmonella enterica subsp. enterica serotype Enteritidis. Two means of infecting the mite were tested: through the blood meal and after cuticular contact. Mites became carriers of Salmonella immediately after the infection with 29% and 53%, respectively, for oral route and cuticular contact. This percentage increased over time until it reached 95% (D7) and 80% (D14). The numerical identification of bacteria on the selective medium SM ID demonstrated the multiplication of Salmonella inside previously infected mites. In addition, transovarial passage as well as transstadial passage (from N1 to N2 stages) were demonstrated. Moreover, the observation of a negative effect of Salmonella on Dermanyssus oviposition was also observed. Finally, previously infected mites were able to contaminate the blood during the blood meal. Therefore, it appears that D. gallinae may act as a biological vector of S. Enteritidis under experimental conditions. It may represent a suitable environment for the development of Salmonella and could be an additional factor for the persistence of salmonellosis infection between successive flocks.

  9. Virulence and site of infection of the fungus, Hirsutella thompsonii, to the honey bee ectoparasitic mite, Varroa destructor.

    PubMed

    Peng, Christine Y S; Zhou, Xinsheng; Kaya, Harry K

    2002-11-01

    The Varroa mite, Varroa destructor, is recognized as the most serious pest of both managed and feral Western honey bee (Apis mellifera) in the world. The mite has developed resistance to fluvalinate, an acaricide used to control it in beehives, and fluvalinate residues have been found in the beeswax, necessitating an urgent need to find alternative control measures to suppress this pest. Accordingly, we investigated the possibility of using the fungus, Hirsutella thompsonii, as a biocontrol agent of the Varroa mite. Among the 9 isolates of H. thompsonii obtained from the University of Florida and the USDA, only the 3 USDA isolates (ARSEF 257, 1947 and 3323) were infectious to the Varroa mite in laboratory tests. The mite became infected when it was allowed to walk on a sporulating H. thompsonii culture for 5 min. Scanning electron micrographs revealed that the membranous arolium of the mite leg sucker is the focus of infection where the fungal conidia adhered and germinated. The infected mites died from mycosis, with the lethal times to kill 50% (LT(50)s) dependent on the fungal isolates. Thus, the LT(50)s were 52.7, 77.2, and 96.7h for isolates 3323, 257, and 1947, respectively. Passage of H. thompsonii through Varroa mite three times significantly reduced the LT(50)s of isolates 257 and 1947 (P<0.05) but not the LT(50) of isolate 3323. The fungus did not infect the honey bee in larval, prepupal, pupal, and adult stages under our laboratory rearing conditions. Our encouraging results suggest that some isolates of H. thompsonii have the potential to be developed as a biocontrol agent for V. destructor. However, fungal infectivity against the mites under beehive conditions needs to be studied before any conclusion can be made.

  10. MITE INFECTION IN A MASKED PALM CIVET (PAGUMA LARVATA) TREATED BY SELAMECTIN (STRONGHOLD®, PFIZER LTD.).

    PubMed

    Olivieri, Lara; Nardini, Giordano; Leopardi, Stefania; Abramo, Francesca

    2015-09-01

    The masked palm civet (Paguma larvata) is a small Asian mammal (order Carnivora, family Viverridae) uncommon in Italy. Limited information is available about management and sanitary maintenance in captivity. A 4-mo-old masked palm civet presented with pruritus, itch, scratching, and disorexia. On physical examination, alopecia and crusts were detected on the ventral and lateral trunk, tail, legs, and lips. Skin scrapings and cytology revealed Notoedres spp. and bacterial infection. On histopathology, parasitic dermatitis was observed with the presence of a Sarcoptidae mite and Demodex spp. Selamectin spot-on (15 mg/kg every 2 wk, three applications) and marbofloxacin per os (2.5 mg/kg once daily for 2 wk) were administered, and the animal recovered in 1 mo. With the good response to this therapy, a notoedric mange was thought to be the main problem. This is the first report about the use of selamectin to treat a mite infection in masked palm civet. PMID:26352967

  11. Ultrastructure and bacterial infection of wounds in honey bee ( Apis mellifera) pupae punctured by Varroa mites.

    PubMed

    Kanbar, G; Engels, W

    2003-08-01

    The damage to western honey bee, Apis mellifera, colonies caused by the originally Asian ectoparasitic mite Varroa destructor is mainly a consequence of the infestation of host bee pupae. In the capped brood cell, female mites puncture the host's integument at preferred sites in order to suck haemolymph. Due to repeated feeding by the mother mite and her progeny, these perforations are kept open until shortly before the imaginal moult of the bee. Thereafter scarring takes place, thus preventing microbial infection after the adult bee has emerged from the protected environment of the sealed brood cell. However, colonies of various bacteria were found in the open wounds of about 15-30% of all inspected host pupae with an abundance depended on the level of host brood cell infestation by the mite. The small punctures of the pupal integument are difficult to detect but, by vital staining with trypan blue, the wounds can be visualised. The ultrastructure of the pupal wounds, the bacterial colonies and the scarring process are documented by a series of scanning electron micrographs.

  12. The prevalence of nasal mite (Pneumonyssoides caninum) infection in Norwegian dogs.

    PubMed

    Bredal, W P

    1998-04-15

    In a prospective study, the skulls of 250 dogs submitted for necropsy during 1993 at the Norwegian College of Veterinary Medicine were examined for the presence of parasites. All skulls were cleaved sagitally, and the frontal sinuses and nasal cavities were visually inspected. Eighteen dogs (7%) had Pneumonyssoides caninum infection at necropsy. No other parasites were observed. Sixteen dogs had heavy or moderate infection scores and 60% of these had concurrent sinusitis. The infected dogs belonged to 14 different breeds, 10 were male and eight were female and they varied in age from four months to 10 years old. Breed distribution, sex and age of the infected dogs did not differ significantly from the total study population. This study indicates that nasal mite infection occurs commonly in Norwegian dogs.

  13. Mitochondrial Genome Sequence of the Scabies Mite Provides Insight into the Genetic Diversity of Individual Scabies Infections

    PubMed Central

    Mofiz, Ehtesham; Seemann, Torsten; Bahlo, Melanie; Holt, Deborah; Currie, Bart J.

    2016-01-01

    The scabies mite, Sarcoptes scabiei, is an obligate parasite of the skin that infects humans and other animal species, causing scabies, a contagious disease characterized by extreme itching. Scabies infections are a major health problem, particularly in remote Indigenous communities in Australia, where co-infection of epidermal scabies lesions by Group A Streptococci or Staphylococcus aureus is thought to be responsible for the high rate of rheumatic heart disease and chronic kidney disease. We collected and separately sequenced mite DNA from several pools of thousands of whole mites from a porcine model of scabies (S. scabiei var. suis) and two human patients (S. scabiei var. hominis) living in different regions of northern Australia. Our sequencing samples the mite and its metagenome, including the mite gut flora and the wound micro-environment. Here, we describe the mitochondrial genome of the scabies mite. We developed a new de novo assembly pipeline based on a bait-and-reassemble strategy, which produced a 14 kilobase mitochondrial genome sequence assembly. We also annotated 35 genes and have compared these to other Acari mites. We identified single nucleotide polymorphisms (SNPs) and used these to infer the presence of six haplogroups in our samples, Remarkably, these fall into two closely-related clades with one clade including both human and pig varieties. This supports earlier findings that only limited genetic differences may separate some human and animal varieties, and raises the possibility of cross-host infections. Finally, we used these mitochondrial haplotypes to show that the genetic diversity of individual infections is typically small with 1–3 distinct haplotypes per infestation. PMID:26872064

  14. Mitochondrial Genome Sequence of the Scabies Mite Provides Insight into the Genetic Diversity of Individual Scabies Infections.

    PubMed

    Mofiz, Ehtesham; Seemann, Torsten; Bahlo, Melanie; Holt, Deborah; Currie, Bart J; Fischer, Katja; Papenfuss, Anthony T

    2016-02-01

    The scabies mite, Sarcoptes scabiei, is an obligate parasite of the skin that infects humans and other animal species, causing scabies, a contagious disease characterized by extreme itching. Scabies infections are a major health problem, particularly in remote Indigenous communities in Australia, where co-infection of epidermal scabies lesions by Group A Streptococci or Staphylococcus aureus is thought to be responsible for the high rate of rheumatic heart disease and chronic kidney disease. We collected and separately sequenced mite DNA from several pools of thousands of whole mites from a porcine model of scabies (S. scabiei var. suis) and two human patients (S. scabiei var. hominis) living in different regions of northern Australia. Our sequencing samples the mite and its metagenome, including the mite gut flora and the wound micro-environment. Here, we describe the mitochondrial genome of the scabies mite. We developed a new de novo assembly pipeline based on a bait-and-reassemble strategy, which produced a 14 kilobase mitochondrial genome sequence assembly. We also annotated 35 genes and have compared these to other Acari mites. We identified single nucleotide polymorphisms (SNPs) and used these to infer the presence of six haplogroups in our samples, Remarkably, these fall into two closely-related clades with one clade including both human and pig varieties. This supports earlier findings that only limited genetic differences may separate some human and animal varieties, and raises the possibility of cross-host infections. Finally, we used these mitochondrial haplotypes to show that the genetic diversity of individual infections is typically small with 1-3 distinct haplotypes per infestation. PMID:26872064

  15. Mitochondrial Genome Sequence of the Scabies Mite Provides Insight into the Genetic Diversity of Individual Scabies Infections.

    PubMed

    Mofiz, Ehtesham; Seemann, Torsten; Bahlo, Melanie; Holt, Deborah; Currie, Bart J; Fischer, Katja; Papenfuss, Anthony T

    2016-02-01

    The scabies mite, Sarcoptes scabiei, is an obligate parasite of the skin that infects humans and other animal species, causing scabies, a contagious disease characterized by extreme itching. Scabies infections are a major health problem, particularly in remote Indigenous communities in Australia, where co-infection of epidermal scabies lesions by Group A Streptococci or Staphylococcus aureus is thought to be responsible for the high rate of rheumatic heart disease and chronic kidney disease. We collected and separately sequenced mite DNA from several pools of thousands of whole mites from a porcine model of scabies (S. scabiei var. suis) and two human patients (S. scabiei var. hominis) living in different regions of northern Australia. Our sequencing samples the mite and its metagenome, including the mite gut flora and the wound micro-environment. Here, we describe the mitochondrial genome of the scabies mite. We developed a new de novo assembly pipeline based on a bait-and-reassemble strategy, which produced a 14 kilobase mitochondrial genome sequence assembly. We also annotated 35 genes and have compared these to other Acari mites. We identified single nucleotide polymorphisms (SNPs) and used these to infer the presence of six haplogroups in our samples, Remarkably, these fall into two closely-related clades with one clade including both human and pig varieties. This supports earlier findings that only limited genetic differences may separate some human and animal varieties, and raises the possibility of cross-host infections. Finally, we used these mitochondrial haplotypes to show that the genetic diversity of individual infections is typically small with 1-3 distinct haplotypes per infestation.

  16. Gene-by-environment effect of house dust mite on purinergic receptor P2Y12 (P2RY12) and lung function in children with asthma

    PubMed Central

    Bunyavanich, Supinda; Boyce, Joshua A.; Raby, Benjamin A.; Weiss, Scott T.

    2012-01-01

    Background Distinct receptors likely exist for leukotriene(LT)E4, a potent mediator of airway inflammation. Purinergic receptor P2Y12 is needed for LTE4-induced airways inflammation, and P2Y12 antagonism attenuates house dust mite-induced pulmonary eosinophilia in mice. Although experimental data support a role for P2Y12 in airway inflammation, its role in human asthma has never been studied. Objective To test for association between variants in the P2Y12 gene (P2RY12) and lung function in human subjects with asthma, and to examine for gene-by-environment interaction with house dust mite exposure. Methods 19 single nucleotide polymorphisms (SNPs) in P2RY12 were genotyped in 422 children with asthma and their parents (n=1266). Using family-based methods, we tested for associations between these SNPs and five lung function measures. We performed haplotype association analyses and tested for gene-by-environment interactions using house dust mite exposure. We used the false discovery rate to account for multiple comparisons. Results Five SNPs in P2RY12 were associated with multiple lung function measures (P values 0.006–0.025). Haplotypes in P2RY12 were also associated with lung function (P values 0.0055–0.046). House dust mite exposure modulated associations between P2RY12 and lung function, with minor allele homozygotes exposed to house dust mite demonstrating worse lung function than those unexposed (significant interaction P values 0.0028–0.040). Conclusions and clinical relevance P2RY12 variants were associated with lung function in a large family-based asthma cohort. House dust mite exposure caused significant gene-by-environment effects. Our findings add the first human evidence to experimental data supporting a role for P2Y12 in lung function. P2Y12 could represent a novel target for asthma treatment. PMID:22010907

  17. Gallium scintigraphic pattern in lung CMV infections

    SciTech Connect

    Ganz, W.I.; Cohen, D.; Mallin, W.

    1994-05-01

    Due to extensive use of prophylactic therapy for Pneumonitis Carinii Pneumonia (PCP), Cytomegalic Viral (CMV) infection may now be the most common lung infection in AIDS patients. This study was performed to determine Gallium-67 patterns in AIDS patients with CMV. Pathology reports were reviewed in AIDS patients who had a dose of 5 to 10 mCi of Gallium-67 citrate. Analysis of images were obtained 48-72 hours later of the entire body was performed. Gallium-67 scans in 14 AIDS patients with biopsy proven CMV, were evaluated for eye, colon, adrenal, lung and renal uptake. These were compared to 40 AIDS patients without CMV. These controls had infections including PCP, Mycobacterial infections, and lymphocytic interstitial pneumonitis. 100% of CMV patients had bowel uptake greater than or equal to liver. Similar bowel activity was seen in 50% of AIDS patients without CMV. 71% had intense eye uptake which was seen in only 10% of patients without CMV. 50% of CMV patients had renal uptake compared to 5% of non-CMV cases. Adrenal uptake was suggested in 50%, however, SPECT imaging is needed for confirmation. 85% had low grade lung uptake. The low grade lung had perihilar prominence. The remaining 15% had high grade lung uptake (greater than sternum) due to superimposed PCP infection. Colon uptake is very sensitive indicator for CMV infection. However, observing eye, renal, and or adrenal uptake improved the diagnostic specificity. SPECT imaging is needed to confirm renal or adrenal abnormalities due to intense bowel activity present in 100% of cases. When high grade lung uptake is seen superimposed PCP is suggested.

  18. Geography has a greater effect than Wolbachia infection on population genetic structure in the spider mite, Tetranychus pueraricola.

    PubMed

    Chen, Y-T; Zhang, Y-K; Du, W-X; Jin, P-Y; Hong, X-Y

    2016-10-01

    Wolbachia is an intracellular symbiotic bacterium that infects various spider mite species and is associated with alterations in host reproduction, which indicates the potential role in mite evolution. However, studies of Wolbachia infections in the spider mite Tetranychus pueraricola, a major agricultural pest, are limited. Here, we used multilocus sequence typing to determine Wolbachia infection status and examined the relationship between Wolbachia infection status and mitochondrial diversity in T. pueraricola from 12 populations in China. The prevalence of Wolbachia ranged from 2.8 to 50%, and three strains (wTpue1, wTpue2, and wTpue3) were identified. We also found double infections (wTpue1 + wTpue3) within the same individuals. Furthermore, the wTpue1 strain caused weak cytoplasmic incompatibility (CI) (egg hatchability ~55%), whereas another widespread strain, wTpue3, did not induce CI. There was no reduction in mitochondrial DNA (mtDNA) or nuclear DNA diversity among infected individuals, and mtDNA haplotypes did not correspond to specific Wolbachia strains. Phylogenetic analysis and analysis of molecular variance revealed that the distribution of mtDNA and nuclear DNA haplotypes were significantly associated with geography. These findings indicate that Wolbachia infection in T. pueraricola is complex, but T. pueraricola genetic differentiation likely resulted from substantial geographic isolation.

  19. Geography has a greater effect than Wolbachia infection on population genetic structure in the spider mite, Tetranychus pueraricola.

    PubMed

    Chen, Y-T; Zhang, Y-K; Du, W-X; Jin, P-Y; Hong, X-Y

    2016-10-01

    Wolbachia is an intracellular symbiotic bacterium that infects various spider mite species and is associated with alterations in host reproduction, which indicates the potential role in mite evolution. However, studies of Wolbachia infections in the spider mite Tetranychus pueraricola, a major agricultural pest, are limited. Here, we used multilocus sequence typing to determine Wolbachia infection status and examined the relationship between Wolbachia infection status and mitochondrial diversity in T. pueraricola from 12 populations in China. The prevalence of Wolbachia ranged from 2.8 to 50%, and three strains (wTpue1, wTpue2, and wTpue3) were identified. We also found double infections (wTpue1 + wTpue3) within the same individuals. Furthermore, the wTpue1 strain caused weak cytoplasmic incompatibility (CI) (egg hatchability ~55%), whereas another widespread strain, wTpue3, did not induce CI. There was no reduction in mitochondrial DNA (mtDNA) or nuclear DNA diversity among infected individuals, and mtDNA haplotypes did not correspond to specific Wolbachia strains. Phylogenetic analysis and analysis of molecular variance revealed that the distribution of mtDNA and nuclear DNA haplotypes were significantly associated with geography. These findings indicate that Wolbachia infection in T. pueraricola is complex, but T. pueraricola genetic differentiation likely resulted from substantial geographic isolation. PMID:27296468

  20. The Effect of Temperature, Relative Humidity, and Virus Infection Status on off-host Survival of the Wheat Curl Mite (Acari: Eriophyidae).

    PubMed

    Wosula, E N; McMechan, A J; Hein, G L

    2015-08-01

    The wheat curl mite, Aceria tosichella Keifer, is an eriophyid pest of wheat, although its primary economic impact on wheat is due to the transmission of Wheat streak mosaic (WSMV), Wheat mosaic (also known as High Plains virus), and Triticum mosaic (TriMV) viruses. These viruses cause significant annual losses in winter wheat production throughout the western Great Plains. Temperature and humidity are factors that often influence arthropod survival, especially during dispersal from their hosts, yet the impact of these two factors on off-host survival has not been documented for wheat curl mite. Pathogen-infected host plants often influence the biology and behavior of vectors, yet it is not known if virus-infected wheat affects off-host survival of wheat curl mite. The objectives of this study were to 1) determine if temperature, relative humidity, and mite genotype impact off-host survival of wheat curl mite and 2) determine the effect of WSMV- and TriMV-infected host plants on off-host survival of wheat curl mite. Temperature and relative humidity significantly affected off-host survival of wheat curl mite. Length of survival decreased with increasing temperature (106.2 h at 10°C and 17.0 h at 30°C) and decreasing relative humidity (78.1 h at 95 and 21.3 h at 2%). Mites from TriMV-infected host plants had ∼20% reduction in survival at 20°C compared with those from WSMV-infected plants. The duration of off-host survival of wheat curl mite is influenced by environmental conditions. Management strategies that target a break in host presence will greatly reduce mite densities and virus spread and need to account for these limits. PMID:26470294

  1. The Effect of Temperature, Relative Humidity, and Virus Infection Status on off-host Survival of the Wheat Curl Mite (Acari: Eriophyidae).

    PubMed

    Wosula, E N; McMechan, A J; Hein, G L

    2015-08-01

    The wheat curl mite, Aceria tosichella Keifer, is an eriophyid pest of wheat, although its primary economic impact on wheat is due to the transmission of Wheat streak mosaic (WSMV), Wheat mosaic (also known as High Plains virus), and Triticum mosaic (TriMV) viruses. These viruses cause significant annual losses in winter wheat production throughout the western Great Plains. Temperature and humidity are factors that often influence arthropod survival, especially during dispersal from their hosts, yet the impact of these two factors on off-host survival has not been documented for wheat curl mite. Pathogen-infected host plants often influence the biology and behavior of vectors, yet it is not known if virus-infected wheat affects off-host survival of wheat curl mite. The objectives of this study were to 1) determine if temperature, relative humidity, and mite genotype impact off-host survival of wheat curl mite and 2) determine the effect of WSMV- and TriMV-infected host plants on off-host survival of wheat curl mite. Temperature and relative humidity significantly affected off-host survival of wheat curl mite. Length of survival decreased with increasing temperature (106.2 h at 10°C and 17.0 h at 30°C) and decreasing relative humidity (78.1 h at 95 and 21.3 h at 2%). Mites from TriMV-infected host plants had ∼20% reduction in survival at 20°C compared with those from WSMV-infected plants. The duration of off-host survival of wheat curl mite is influenced by environmental conditions. Management strategies that target a break in host presence will greatly reduce mite densities and virus spread and need to account for these limits.

  2. Effect of the oral thrombin inhibitor dabigatran on allergic lung inflammation induced by repeated house dust mite administration in mice.

    PubMed

    de Boer, Johannes D; Berkhout, Lea C; de Stoppelaar, Sacha F; Yang, Jack; Ottenhoff, Roelof; Meijers, Joost C M; Roelofs, Joris J T H; van't Veer, Cornelis; van der Poll, Tom

    2015-10-15

    Asthma is a chronic disease of the airways; asthma patients are hampered by recurrent symptoms of dyspnoea and wheezing caused by bronchial obstruction. Most asthma patients suffer from chronic allergic lung inflammation triggered by allergens such as house dust mite (HDM). Coagulation activation in the pulmonary compartment is currently recognized as a feature of allergic lung inflammation, and data suggest that coagulation proteases further drive inflammatory mechanisms. Here, we tested whether treatment with the oral thrombin inhibitor dabigatran attenuates allergic lung inflammation in a recently developed HDM-based murine asthma model. Mice were fed dabigatran (10 mg/g) or placebo chow during a 3-wk HDM airway exposure model. Dabigatran treatment caused systemic thrombin inhibitory activity corresponding with dabigatran levels reported in human trials. Surprisingly, dabigatran did not lead to inhibition of HDM-evoked coagulation activation in the lung as measured by levels of thrombin-antithrombin complexes and D-dimer. Repeated HDM administration caused an influx of eosinophils and neutrophils into the lungs, mucus production in the airways, and a T helper 2 response, as reflected by a rise in bronchoalveolar IL-4 and IL-5 levels and a systemic rise in IgE and HDM-IgG1. Dabigatran modestly improved HDM-induced lung pathology (P < 0.05) and decreased IL-4 levels (P < 0.01), without influencing other HDM-induced responses. Considering the limited effects of dabigatran in spite of adequate plasma levels, these results argue against clinical evaluation of dabigatran in patients with asthma.

  3. Lung cancer in HIV-infected patients

    PubMed Central

    Palacios, R; Lebrón, J; Guerrero-León, M; Del Arco, A; Colmenero, J; Márquez, M; Santos, J

    2012-01-01

    Purpose Several studies have shown that HIV patients are at higher risk of lung cancer. Our aim is to analyse the prevalence and features of lung cancer in HIV-infected patients. Methods The clinical charts of 4,721 HIV-infected patients seen in three hospitals of southeast Spain (study period 1992–2012) were reviewed, and all patients with a lung cancer were analysed. Results There were 61 lung cancers, giving a prevalence of 1.2%. There was a predominance of men (82.0%), and smokers (96.6%; mean pack-years 35.2), with a median age of 48.0 (41.7–52.9) years, and their distribution according to risk group for HIV was: intravenous drug use 58.3%, homosexual 20.0%, and heterosexual 16.7%. Thirty-four (56.7%) patients were Aids cases, and 29 (47.5%) had prior pulmonar events: tuberculosis 16, bacterial pneumonia 9, and P. jiroveci pneumonia 4. The median nadir CD4 count was 149/mm3 (42–232), the median CD4 count at the time of diagnosis of the lung cancer was 237/mm3 (85–397), and 66.1%<350/mm3. 66.7% were on ART, and 70% of them had undetectable HIV viral load. The most common histological types of lung cancer were adenocarcinoma and epidermoid, with 24 (40.0%) and 23 (38.3%) cases, respectively. There were 49 (80.3%) cases with advanced stages (III and IV) at diagnosis. The distribution of treatments was: only palliative 23 (39.7%), chemotherapy 14 (24.1%), surgery and chemotherapy 8 (13.8%), radiotherapy 7 (12.1%), surgery 4 (6.9%), and other combined treatments 2 (3.4%). Forty-six (76.7%) patients died, with a median survival time of 3 months. The Kaplan-Meier survival rate at 6 months was 42.7% (at 12 months 28.5%). Conclusions The prevalence of lung cancer in this cohort of HIV-patients is high. People affected are mainly men, smokers, with transmission of HIV by intravenous drug use, and around half of them with prior opportunistic pulmonary events. Most patients had low nadir CD4 count, and were immunosuppressed at the time of diagnosis. Adenocarcinoma

  4. Lower Virus Infections in Varroa destructor-Infested and Uninfested Brood and Adult Honey Bees (Apis mellifera) of a Low Mite Population Growth Colony Compared to a High Mite Population Growth Colony

    PubMed Central

    Emsen, Berna; Hamiduzzaman, Mollah Md.; Goodwin, Paul H.; Guzman-Novoa, Ernesto

    2015-01-01

    A comparison was made of the prevalence and relative quantification of deformed wing virus (DWV), Israeli acute paralysis virus (IAPV), black queen cell virus (BQCV), Kashmir bee virus (KBV), acute bee paralysis virus (ABPV) and sac brood virus (SBV) in brood and adult honey bees (Apis mellifera) from colonies selected for high (HMP) and low (LMP) Varroa destructor mite population growth. Two viruses, ABPV and SBV, were never detected. For adults without mite infestation, DWV, IAPV, BQCV and KBV were detected in the HMP colony; however, only BQCV was detected in the LMP colony but at similar levels as in the HMP colony. With mite infestation, the four viruses were detected in adults of the HMP colony but all at higher amounts than in the LMP colony. For brood without mite infestation, DWV and IAPV were detected in the HMP colony, but no viruses were detected in the LMP colony. With mite infestation of brood, the four viruses were detected in the HMP colony, but only DWV and IAPV were detected and at lower amounts in the LMP colony. An epidemiological explanation for these results is that pre-experiment differences in virus presence and levels existed between the HMP and LMP colonies. It is also possible that low V. destructor population growth in the LMP colony resulted in the bees being less exposed to the mite and thus less likely to have virus infections. LMP and HMP bees may have also differed in susceptibility to virus infection. PMID:25723540

  5. Lower virus infections in Varroa destructor-infested and uninfested brood and adult honey bees (Apis mellifera) of a low mite population growth colony compared to a high mite population growth colony.

    PubMed

    Emsen, Berna; Hamiduzzaman, Mollah Md; Goodwin, Paul H; Guzman-Novoa, Ernesto

    2015-01-01

    A comparison was made of the prevalence and relative quantification of deformed wing virus (DWV), Israeli acute paralysis virus (IAPV), black queen cell virus (BQCV), Kashmir bee virus (KBV), acute bee paralysis virus (ABPV) and sac brood virus (SBV) in brood and adult honey bees (Apis mellifera) from colonies selected for high (HMP) and low (LMP) Varroa destructor mite population growth. Two viruses, ABPV and SBV, were never detected. For adults without mite infestation, DWV, IAPV, BQCV and KBV were detected in the HMP colony; however, only BQCV was detected in the LMP colony but at similar levels as in the HMP colony. With mite infestation, the four viruses were detected in adults of the HMP colony but all at higher amounts than in the LMP colony. For brood without mite infestation, DWV and IAPV were detected in the HMP colony, but no viruses were detected in the LMP colony. With mite infestation of brood, the four viruses were detected in the HMP colony, but only DWV and IAPV were detected and at lower amounts in the LMP colony. An epidemiological explanation for these results is that pre-experiment differences in virus presence and levels existed between the HMP and LMP colonies. It is also possible that low V. destructor population growth in the LMP colony resulted in the bees being less exposed to the mite and thus less likely to have virus infections. LMP and HMP bees may have also differed in susceptibility to virus infection.

  6. Transthyretin as a potential biomarker for the differential diagnosis between lung cancer and lung infection

    PubMed Central

    DING, HONGMEI; LIU, JIANHUA; XUE, RONG; ZHAO, PENG; QIN, YI; ZHENG, FANG; SUN, XUGUO

    2014-01-01

    Satisfactory biomarkers for screening and early diagnosis of lung cancer remain scarce and require further investigation. The aim of the present study was to examine the changes of the biochemical and protein composition in the serum and pleural effusion from lung cancer and lung infection (bacterial pneumonia) patients. A total of 92 patients with lung cancer, 38 with bacterial pneumonia and 42 healthy controls were enrolled in the study. The serum levels of cholesterol, apolipoprotein A and transthyretin (TTR) in the lung cancer patients were higher than that of the lung infection patients (P<0.05). The levels of TTR were higher, whereas the activity of adenosine deaminase (ADA) was lower in the pleural effusion from the lung cancer patients compared to the lung infection patients (P<0.05). Furthermore, the pleural effusion/serum TTR ratios in the lung cancer patients were higher, whereas the ratios of ADA were lower (P<0.05). By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, four major peaks corresponding to native TTR, Sul-TTR, Cys-TTR and Cysgly-TTR were observed in the serum of the lung cancer and lung infection patients. A significant increase was found in the proportion of Cysgly-TTR in the pleural effusion from the patients with lung cancer. The data indicated that a combination of pleural effusion/serum TTR ratios and modified TTR may be beneficial for the differential diagnosis between lung cancer and lung infection. PMID:25054025

  7. A Lung Segmental Model of Chronic Pseudomonas Infection in Sheep

    PubMed Central

    Collie, David; Govan, John; Wright, Steven; Thornton, Elisabeth; Tennant, Peter; Smith, Sionagh; Doherty, Catherine; McLachlan, Gerry

    2013-01-01

    Background Chronic lung infection with Pseudomonas aeruginosa is a major contributor to morbidity, mortality and premature death in cystic fibrosis. A new paradigm for managing such infections is needed, as are relevant and translatable animal models to identify and test concepts. We sought to improve on limitations associated with existing models of infection in small animals through developing a lung segmental model of chronic Pseudomonas infection in sheep. Methodology/Principal Findings Using local lung instillation of P. aeruginosa suspended in agar beads we were able to demonstrate that such infection led to the development of a suppurative, necrotising and pyogranulomatous pneumonia centred on the instilled beads. No overt evidence of organ or systemic compromise was apparent in any animal during the course of infection. Infection persisted in the lungs of individual animals for as long as 66 days after initial instillation. Quantitative microbiology applied to bronchoalveolar lavage fluid derived from infected segments proved an insensitive index of the presence of significant infection in lung tissue (>104 cfu/g). Conclusions/Significance The agar bead model of chronic P. aeruginosa lung infection in sheep is a relevant platform to investigate both the pathobiology of such infections as well as novel approaches to their diagnosis and therapy. Particular ethical benefits relate to the model in terms of refining existing approaches by compromising a smaller proportion of the lung with infection and facilitating longitudinal assessment by bronchoscopy, and also potentially reducing animal numbers through facilitating within-animal comparisons of differential therapeutic approaches. PMID:23874438

  8. Screening of spider mites (Acari: Tetranychidae) for reproductive endosymbionts reveals links between co-infection and evolutionary history.

    PubMed

    Zhang, Yan-Kai; Chen, Ya-Ting; Yang, Kun; Qiao, Ge-Xia; Hong, Xiao-Yue

    2016-01-01

    Reproductive endosymbionts have been shown to have wide-ranging effects on many aspects of their hosts' biology. A first step to understanding how these endosymbionts interact with their hosts is to determine their incidences. Here, we screened for four reproductive endosymbionts (Wolbachia, Cardinium, Spiroplasma and Rickettsia) in 28 populations of spider mites (Acari: Tetranychidae) representing 12 species. Each of the four endosymbionts were identified in at least some of the tested specimens, and their infection patterns showed variations at the species-level and population-level, suggesting their distributions can be correlated with both the phylogeny and ecology of the hosts. Co-infections of unrelated bacteria, especially double infections of Wolbachia and Cardinium within the same individuals were common. Spiroplasma and Rickettsia infections were specific to particular host species, respectively. Further, the evolutionary histories of these endosymbionts were inferred by comparing the phylogenies of them and their hosts. These findings can help to clarify the interactions between endosymbionts and arthropods.

  9. Field study on the efficacy of an extract of neem seed (Mite -Stop) against the red mite Dermanyssus gallinae naturally infecting poultry in Egypt.

    PubMed

    Abdel-Ghaffar, Fathy; Sobhy, Hassan M; Al-Quraishy, Saleh; Semmler, Margit

    2008-08-01

    Infestations with the poultry red mite Dermanyssus gallinae represent a major ectoparasite problem in poultry and affects egg and meat production worldwide. The effects of the neem seed product Mite-Stop against the red poultry mite were investigated. Five primitive poultry farms in two small villages in the Nile Delta and Giza district were selected for the study. The neem extract was diluted 1:40 and 1:50 with tap water just prior to use. Application of the two dilutions of the provided product was performed to soil, cracks and crevices of the examined area as well as to mite-infested birds on day 0 and day 7. Two hours after treatment soil dust was collected from sprayed regions of the stable and from unsprayed control regions of the same stable. The treated chickens were also checked for mites 2 h after each treatment. The examination of the chickens 2 h after spraying showed that they were free of mites. The examination of treated soil with the Tullgren funnel apparatus 2 h after the first spraying on day 0 already showed a considerable reduction of living mites compared to controls. Seven days after the first treatment of the soil the number of living mites was reduced for 80% in the treated soil and decreased even more after the second spraying, since those larvae that had hatched from eggs in the meantime were killed. The 1:40 dilution of the neem seed extract with tap water was superior to the 1:50 dilution. These results clearly show a very high killing rate of the extract, if the mites come in direct contact with the compound. However, in order to obtain extinction also of hidden and freshly hatched stages repeated spraying should be done three times within 8-10 days. PMID:18481087

  10. Early airway infection, inflammation, and lung function in cystic fibrosis

    PubMed Central

    Nixon, G; Armstrong, D; Carzino, R; Carlin, J; Olinsky, A; Robertson, C; Grimwood, K

    2002-01-01

    Aims: To determine the relation between lower airway infection and inflammation, respiratory symptoms, and lung function in infants and young children with cystic fibrosis (CF). Methods: A prospective study of children with CF aged younger than 3 years, diagnosed by a newborn screening programme. All were clinically stable and had testing as outpatients. Subjects underwent bronchial lavage (BL) and lung function testing by the raised volume rapid thoracoabdominal compression technique under general anaesthesia. BL fluid was cultured and analysed for neutrophil count, interleukin 8, and neutrophil elastase. Lung function was assessed by forced expiratory volume in 0.5, 0.75, and 1 second. Results: Thirty six children with CF were tested on 54 occasions. Lower airway infection shown by BL was associated with a 10% reduction in FEV0.5 compared with subjects without infection. No relation was identified between airway inflammation and lung function. Daily moist cough within the week before testing was reported on 20/54 occasions, but in only seven (35%) was infection detected. Independent of either infection status or airway inflammation, those with daily cough had lower lung function than those without respiratory symptoms at the time of BL (mean adjusted FEV0.5 195 ml and 236 ml respectively). Conclusions: In young children with CF, both respiratory symptoms and airway infection have independent, additive effects on lung function, unrelated to airway inflammation. Further studies are needed to understand the mechanisms of airway obstruction in these young patients. PMID:12244003

  11. Ex Vivo Perfusion Treatment of Infection in Human Donor Lungs.

    PubMed

    Nakajima, D; Cypel, M; Bonato, R; Machuca, T N; Iskender, I; Hashimoto, K; Linacre, V; Chen, M; Coutinho, R; Azad, S; Martinu, T; Waddell, T K; Hwang, D M; Husain, S; Liu, M; Keshavjee, S

    2016-04-01

    Ex vivo lung perfusion (EVLP) is a platform to treat infected donor lungs with antibiotic therapy before lung transplantation. Human donor lungs that were rejected for transplantation because of clinical concern regarding infection were randomly assigned to two groups. In the antibiotic group (n = 8), lungs underwent EVLP for 12 h with high-dose antibiotics (ciprofloxacin 400 mg or azithromycin 500 mg, vancomycin 15 mg/kg, and meropenem 2 g). In the control group (n = 7), lungs underwent EVLP for 12 h without antibiotics. A quantitative decrease in bacterial counts in bronchoalveolar lavage (BAL) was found in all antibiotic-treated cases but in only two control cases. Perfusate endotoxin levels at 12 h were significantly lower in the antibiotic group compared with the control group. EVLP with broad-spectrum antibiotic therapy significantly improved pulmonary oxygenation and compliance and reduced pulmonary vascular resistance. Perfusate endotoxin levels at 12 h were strongly correlated with levels of perfusates tumor necrosis factor α, IL-1β and macrophage inflammatory proteins 1α and 1β at 12 h. In conclusion, EVLP treatment of infected donor lungs with broad-spectrum antibiotics significantly reduced BAL bacterial counts and endotoxin levels and improved donor lung function. PMID:26730551

  12. An epidemiological survey of therapy and diagnostic procedures used by Norwegian small animal practitioners in cases of nasal mite (Pneumonyssoides caninum) infection in dogs.

    PubMed

    Bredal, W P

    1998-09-01

    Forty per cent of the members of the Norwegian Small Animal Veterinary Association (NSAVA) returned a questionnaire regarding the treatment and diagnosis of canine nasal mite infection in their practices in 1996. A total of 2392 dogs were treated for this infection by 156 NSAVA members in clinical practice in that year, averaging 15.3 treated dogs per veterinarian. An estimated minimum of 6000 Norwegian dogs were treated for nasal mite infection in 1996, at an estimated cost of treatment exceeding 3.3 million NOK. Fifty-nine per cent of the practitioners included at least a case history and clinical examination as diagnostic criteria prior to initiating treatment for nasal mite infection. Fewer than 10% routinely performed more thorough diagnostic procedures, and only 1.8% of the diagnoses were verified prior to treatment. A total of 27 different treatment regimens, involving either subcutaneously injected ivermectin or orally administered milbemycin oxime, were routinely used by NSAVA veterinarians to treat these dogs. Seventy-two (53%) of the veterinarians used ivermectin exclusively, 14 (10%) used milbemycin oxime exclusively, while 50 (37%) used both ivermectin and milbemycin oxime. No other drugs were used. Evaluation of treatment was made by assessing resolution of the clinical signs following treatment, and 97% of the veterinarians were satisfied with the effect of the treatment regimen they used. Adverse side-effects following treatment for nasal mite infection in 1996 were seen on 9 occasions; 4 following ivermectin administration and 2 following milbemycin oxime treatment, while in 3 cases no information on the drug used was provided. The risk of adverse reactions to treatment of nasal mite infection in dogs was 0.4%.

  13. The association between human papillomavirus infection and female lung cancer

    PubMed Central

    Lin, Frank Cheau-Feng; Huang, Jing-Yang; Tsai, Stella Ching-Shao; Nfor, Oswald Ndi; Chou, Ming-Chih; Wu, Ming-Fang; Lee, Chun-Te; Jan, Cheng-Feng; Liaw, Yung-Po

    2016-01-01

    Abstract Lung cancer is the leading cause of cancer deaths among Taiwanese women. Human papillomavirus (HPV) has been detected in lung cancer tissues. The aim of this study was to investigate the association between HPV infection and lung cancer among the Taiwanese women. The analytical data were collected from the longitudinal health insurance databases (LHID 2005 and 2010) of the National Health Insurance Research Database (NHIRD). The study participants were 30 years and older and included 24,162 individuals who were identified with HPV infection from 2001 to 2004 and 1,026,986 uninfected individuals. Lung cancer incidence among infected and uninfected individuals was compared using the univariate and multivariate regression models. Among the total participants, 24,162 individuals were diagnosed with HPV. After adjusting for age, gender, low income, residential area, and comorbidity, the risk of lung cancer was higher in women (hazard ratio [HR] 1.263, 95% CI 1.015–1.571), while all cancer risks were high in both men and women with corresponding hazard ratios (HR) of 1.161 (95% CI 1.083–1.245) and HR 1.240 (95% CI 1.154–1.331), respectively. This study showed a significant increase in lung cancer risk among Taiwanese women who were exposed to HPV infection. PMID:27281096

  14. Screening of spider mites (Acari: Tetranychidae) for reproductive endosymbionts reveals links between co-infection and evolutionary history.

    PubMed

    Zhang, Yan-Kai; Chen, Ya-Ting; Yang, Kun; Qiao, Ge-Xia; Hong, Xiao-Yue

    2016-01-01

    Reproductive endosymbionts have been shown to have wide-ranging effects on many aspects of their hosts' biology. A first step to understanding how these endosymbionts interact with their hosts is to determine their incidences. Here, we screened for four reproductive endosymbionts (Wolbachia, Cardinium, Spiroplasma and Rickettsia) in 28 populations of spider mites (Acari: Tetranychidae) representing 12 species. Each of the four endosymbionts were identified in at least some of the tested specimens, and their infection patterns showed variations at the species-level and population-level, suggesting their distributions can be correlated with both the phylogeny and ecology of the hosts. Co-infections of unrelated bacteria, especially double infections of Wolbachia and Cardinium within the same individuals were common. Spiroplasma and Rickettsia infections were specific to particular host species, respectively. Further, the evolutionary histories of these endosymbionts were inferred by comparing the phylogenies of them and their hosts. These findings can help to clarify the interactions between endosymbionts and arthropods. PMID:27291078

  15. Screening of spider mites (Acari: Tetranychidae) for reproductive endosymbionts reveals links between co-infection and evolutionary history

    PubMed Central

    Zhang, Yan-Kai; Chen, Ya-Ting; Yang, Kun; Qiao, Ge-Xia; Hong, Xiao-Yue

    2016-01-01

    Reproductive endosymbionts have been shown to have wide-ranging effects on many aspects of their hosts’ biology. A first step to understanding how these endosymbionts interact with their hosts is to determine their incidences. Here, we screened for four reproductive endosymbionts (Wolbachia, Cardinium, Spiroplasma and Rickettsia) in 28 populations of spider mites (Acari: Tetranychidae) representing 12 species. Each of the four endosymbionts were identified in at least some of the tested specimens, and their infection patterns showed variations at the species-level and population-level, suggesting their distributions can be correlated with both the phylogeny and ecology of the hosts. Co-infections of unrelated bacteria, especially double infections of Wolbachia and Cardinium within the same individuals were common. Spiroplasma and Rickettsia infections were specific to particular host species, respectively. Further, the evolutionary histories of these endosymbionts were inferred by comparing the phylogenies of them and their hosts. These findings can help to clarify the interactions between endosymbionts and arthropods. PMID:27291078

  16. The effect of house dust mite sensitization on lung size and airway caliber in symptomatic and nonsymptomatic preadolescent children: a community-based study in Poland.

    PubMed Central

    Jedrychowski, Wieslaw; Maugeri, Umberto; Jedrychowska-Bianchi, Iwona; Mróz, Elzbieta

    2002-01-01

    There are conflicting reports on the effects of atopy on lung function. The purpose of this study was to compare the effects of house mite (HM) atopy on lung function in subsamples of 12-year-old symptomatic and nonsymptomatic preadolescent children taken from the community sample. An additional objective of this study was to identify possible environmental determinants of HM skin reaction. We obtained questionnaire data on respiratory symptoms and skin-prick tests and performed spirometry on a subsample of 311 children of a birth cohort of children who have been followed over 3 years. Multivariate regression analysis showed progressive decrement of lung function indices (forced vital capacity, forced expiratory volume in 1 sec, and forced expiratory flow, midexpiratory phase) with increasing degree of HM atopy reflected by the skin reaction to HM allergens. The apparent association between the level of HM atopy and the lung function indices was highly significant in symptomatic individuals but insignificant in nonsymptomatic subjects. HM sensitization was significantly associated with mother's atopy. It occurred predominantly in boys and was related to the use of coal or gas for house heating. The effect of allergen sensitization on lung size and airway caliber confined to symptomatic subjects may reflect the inflammatory status of bronchial airways in the symptomatic subjects. PMID:12055047

  17. Primary pulmonary botryomycosis: a bacterial lung infection mimicking lung cancer.

    PubMed

    Ariza-Prota, M A; Pando-Sandoval, A; García-Clemente, M; Jiménez, H; Álvarez-Álvarez, C; Casan-Clara, P

    2013-07-01

    Primary pulmonary botryomycosis, or bacterial pseudomycosis, is an unusual bacterial infection characterised by the formation of eosinophilic granules that resemble those of Actinomyces species infection. The diagnosis of botryomycosis is based on culture of the granules revealing gram-positive cocci or gram-negative bacilli. The bacterial pathogen most frequently found is Staphylococcus aureus. The pathobiology remains unknown. Pulmonary botryomycosis can resemble actinomycosis, tuberculosis or invasive carcinoma. Definitive treatment requires a combination of both surgical debridement and long-term antimicrobial therapy. We present a case of primary pulmonary botryomycosis in an immunocompetent patient.

  18. Interleukin-33 from Monocytes Recruited to the Lung Contributes to House Dust Mite-Induced Airway Inflammation in a Mouse Model

    PubMed Central

    Tashiro, Hiroki; Takahashi, Koichiro; Hayashi, Shinichiro; Kato, Go; Kurata, Keigo; Kimura, Shinya; Sueoka-Aragane, Naoko

    2016-01-01

    Background Interleukin-33 (IL-33) activates group 2 innate lymphoid cells (ILC2), resulting in T-helper-2 inflammation in bronchial asthma. Airway epithelial cells were reported as sources of IL-33 during apoptosis and necrosis. However, IL-33 is known to be from sources other than airway epithelial cells such as leukocytes, and the mechanisms of IL-33 production and release are not fully understood. The aim of this study was to clarify the role of IL-33 production by monocytes in airway inflammation. Methods BALB/c mice were sensitized and challenged with a house dust mite (HDM) preparation. Airway inflammation was assessed by quantifying inflammatory cells in bronchoalveolar lavage (BAL) fluid, and IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) levels in lung. Immunohistochemistry for IL-33 in lung sections was also performed. Ly6c, CD11b, and CD11c expression was examined by flow cytometry. Clodronate liposomes were used in the HDM-airway inflammation model to deplete circulating monocytes. Results The IL-33, but not IL-25 or TSLP, level in lung homogenates was markedly increased in HDM mice compared to control mice. IL-33-positive cells in the lungs were identified using immunohistochemistry and were increased in areas surrounding bronchi and vasculature. Furthermore, IL-33 levels were increased in mononuclear cells derived from lungs of HDM mice compared to controls. The expression of Ly6c in mononuclear cells was significantly higher in HDM mice than in controls. Treatment with clodronate liposomes led to inhibition of not only inflammatory cells in BAL fluid, airway hyper reactivity and Th2 cytokines in lung, but also IL-33 in lung. Conclusion IL-33 from monocytes recruited to the lung may contribute to the pathogenesis of HDM-induced airway inflammation. PMID:27310495

  19. Necrotizing lung infection caused by the protozoan Balantidium coli

    PubMed Central

    Sharma, Sat; Harding, Godfrey

    2003-01-01

    Balantidium coli, a ciliated protozoan, is well known to cause intestinal infection in humans. Extraintestinal spread to the peritoneal cavity and genitourinary tract has rarely been reported. There have also been a few cases of lung involvement from this parasite. A case of B coli causing a thick-walled right upper lobe cavity in an organic farmer who had contact with aerosolized pig manure is reported. Bronchoalveolar lavage fluid examined for ova and parasite revealed trophozoites of B coli in large numbers. Treatment with doxycycline hyclate led to marked improvement. Necrotizing lung infection caused by the protozoan B coli should be considered in individuals who report contact with pigs. PMID:18159451

  20. Necrotizing lung infection caused by the protozoan Balantidium coli.

    PubMed

    Sharma, Sat; Harding, Godfrey

    2003-05-01

    Balantidium coli, a ciliated protozoan, is well known to cause intestinal infection in humans. Extraintestinal spread to the peritoneal cavity and genitourinary tract has rarely been reported. There have also been a few cases of lung involvement from this parasite. A case of B coli causing a thick-walled right upper lobe cavity in an organic farmer who had contact with aerosolized pig manure is reported. Bronchoalveolar lavage fluid examined for ova and parasite revealed trophozoites of B coli in large numbers. Treatment with doxycycline hyclate led to marked improvement. Necrotizing lung infection caused by the protozoan B coli should be considered in individuals who report contact with pigs. PMID:18159451

  1. Bacteriocin-mediated competition in cystic fibrosis lung infections

    PubMed Central

    Ghoul, Melanie; West, Stuart A.; Johansen, Helle Krogh; Molin, Søren; Harrison, Odile B.; Maiden, Martin C. J.; Jelsbak, Lars; Bruce, John B.; Griffin, Ashleigh S.

    2015-01-01

    Bacteriocins are toxins produced by bacteria to kill competitors of the same species. Theory and laboratory experiments suggest that bacteriocin production and immunity play a key role in the competitive dynamics of bacterial strains. The extent to which this is the case in natural populations, especially human pathogens, remains to be tested. We examined the role of bacteriocins in competition using Pseudomonas aeruginosa strains infecting lungs of humans with cystic fibrosis (CF). We assessed the ability of different strains to kill each other using phenotypic assays, and sequenced their genomes to determine what bacteriocins (pyocins) they carry. We found that (i) isolates from later infection stages inhibited earlier infecting strains less, but were more inhibited by pyocins produced by earlier infecting strains and carried fewer pyocin types; (ii) this difference between early and late infections appears to be caused by a difference in pyocin diversity between competing genotypes and not by loss of pyocin genes within a lineage over time; (iii) pyocin inhibition does not explain why certain strains outcompete others within lung infections; (iv) strains frequently carry the pyocin-killing gene, but not the immunity gene, suggesting resistance occurs via other unknown mechanisms. Our results show that, in contrast to patterns observed in experimental studies, pyocin production does not appear to have a major influence on strain competition during CF lung infections. PMID:26311664

  2. Paragonimus kellicotti: A Lung Infection in Our Own Backyard

    PubMed Central

    Johannesen, Eric; Nguyen, Van

    2016-01-01

    Paragonimiasis is an infection caused by the lung fluke of the genus Paragonimus. Within the United States, paragonimiasis has been commonly diagnosed in Southeast Asian immigrants infected with the Asian lung fluke Paragonimus westermani. Infections from the North American lung fluke, Paragonimus kellicotti, have been rare, although more infections have been seen in people in the Midwestern United States. A 29-year-old male with a history of pleomorphic xanthoastrocytoma presented with hemoptysis. A CT scan showed a mass in the left upper lung lobe. A biopsy showed eosinophils and parasite eggs, some with a recognizable operculum. Further investigation revealed that he takes canoe trips on rivers within Missouri and would eat crayfish caught from these rivers. A blood sample was confirmed positive for Paragonimiasis serologically at the Center for Disease Control. Paragonimus kellicotti is found in rivers within the Mississippi basin. Infection occurs by consuming uncooked or undercooked crawfish. Microscopic identification of parasite eggs has been the gold standard. Serologic tests have been developed to aid in the diagnosis. Patients typically present with fever and hemoptysis. Common CT findings include pleural effusion, a mass, and lymphadenopathy. Awareness of P. kellicotti is important to guide appropriate diagnostic testing and ensuring proper treatment. PMID:27213066

  3. Paragonimus kellicotti: A Lung Infection in Our Own Backyard.

    PubMed

    Johannesen, Eric; Nguyen, Van

    2016-01-01

    Paragonimiasis is an infection caused by the lung fluke of the genus Paragonimus. Within the United States, paragonimiasis has been commonly diagnosed in Southeast Asian immigrants infected with the Asian lung fluke Paragonimus westermani. Infections from the North American lung fluke, Paragonimus kellicotti, have been rare, although more infections have been seen in people in the Midwestern United States. A 29-year-old male with a history of pleomorphic xanthoastrocytoma presented with hemoptysis. A CT scan showed a mass in the left upper lung lobe. A biopsy showed eosinophils and parasite eggs, some with a recognizable operculum. Further investigation revealed that he takes canoe trips on rivers within Missouri and would eat crayfish caught from these rivers. A blood sample was confirmed positive for Paragonimiasis serologically at the Center for Disease Control. Paragonimus kellicotti is found in rivers within the Mississippi basin. Infection occurs by consuming uncooked or undercooked crawfish. Microscopic identification of parasite eggs has been the gold standard. Serologic tests have been developed to aid in the diagnosis. Patients typically present with fever and hemoptysis. Common CT findings include pleural effusion, a mass, and lymphadenopathy. Awareness of P. kellicotti is important to guide appropriate diagnostic testing and ensuring proper treatment. PMID:27213066

  4. Transcriptional responses in eastern honeybees (Apis cerana) infected with mites, Varroa destructor.

    PubMed

    Ji, T; Yin, L; Liu, Z; Liang, Q; Luo, Y; Shen, J; Shen, F

    2014-10-31

    The Varroa destructor mite has become the greatest threat to Apis mellifera health worldwide, but rarely causes serious damage to its native host Apis cerana. Understanding the resistance mechanisms of eastern bees against Varroa mites will help researchers determine how to protect other species from this organism. The A. cerana genome has not been previously sequenced; hence, here we sequenced the A. cerana nurse workers transcriptome and monitored the differential gene expression of A. cerana bees challenged by V. destructor. Using de novo transcriptome assembly, we obtained 91,172 unigenes (transcripts) for A. cerana. Differences in gene expression levels between the unchallenged (Con) and challenged (Con2) samples were estimated, and a total of 36,691 transcripts showed a 2-fold difference (at least) between the 2 libraries. A total of 272 differentially expressed genes showed differences greater than 15-fold, and 265 unigenes were present at higher levels in Con2 than in Con. Among the upregulated unigenes in the Con2 colony, genes related to skeletal muscle movement (troponin and calcium-transporting ATPase), olfactory sensitivity (odorant binding proteins, and Down syndrome cell adhesion molecule gene) and transcription factors (cyclic adenosine monophosphate-responsive element-binding protein and transcription factor mblk-1) appeared to be involved in Varroa resistance. Real-time polymerase chain reaction was performed to validate these differentially expressed genes screened by the sequencing approach, and sufficient consistency was observed between the two methods. These findings strongly support that hygienic and grooming behaviors play important roles in Varroa resistance.

  5. Demodex mites.

    PubMed

    Elston, Carly A; Elston, Dirk M

    2014-01-01

    Demodex mites are normal inhabitants of human hair follicles. D folliculorum is found predominantly in the follicular infundibulum of facial skin and is typically present in small groups. D brevis, the smaller of the two species, predominates on the trunk, typically as solitarily mites within the sebaceous glands and ducts. In a wide variety of animals, Demodex mites are recognized as a cause of mange. The role of Demodex mites as agents of human disease has been more controversial, but evidence favors their involvement in acneiform eruptions, folliculitis, and a range of eruptions in immunosuppressed patients. PMID:25441466

  6. Demodex mites.

    PubMed

    Elston, Carly A; Elston, Dirk M

    2014-01-01

    Demodex mites are normal inhabitants of human hair follicles. D folliculorum is found predominantly in the follicular infundibulum of facial skin and is typically present in small groups. D brevis, the smaller of the two species, predominates on the trunk, typically as solitarily mites within the sebaceous glands and ducts. In a wide variety of animals, Demodex mites are recognized as a cause of mange. The role of Demodex mites as agents of human disease has been more controversial, but evidence favors their involvement in acneiform eruptions, folliculitis, and a range of eruptions in immunosuppressed patients.

  7. Characterization Based on the 56-Kda Type-Specific Antigen Gene of Orientia tsutsugamushi Genotypes Isolated from Leptotrombidium Mites and the Rodent Host Post-Infection

    PubMed Central

    Takhampunya, Ratree; Tippayachai, Bousaraporn; Promsathaporn, Sommai; Leepitakrat, Surachai; Monkanna, Taweesak; Schuster, Anthony L.; Melendrez, Melanie C.; Paris, Daniel H.; Richards, Allen L.; Richardson, Jason H.

    2014-01-01

    Characterization of the 56-kDa type-specific antigen (TSA) genes of Orientia tsutsugamushi (OT) from three naturally infected, laboratory-reared mite colonies comprising three species (Leptotrombidium deliense [Ld], Leptotrombidium imphalum [Li], and Leptotrombidium chiangraiensis [Lc]) has revealed the presence of single and coexisting OT genotypes found in individual chiggers. The Karp genotype was found in all of the chiggers examined, whereas Gilliam and UT302 genotypes were only observed in combination with the Karp genotype. From analysis of these OT genotypes after transmission from chiggers to mice it was determined that with the Lc and Li mites, the OT genotype composition in the rodent spleens post-infection had not changed and therefore resembled that observed in the feeding chiggers. However, only the Karp genotype was found in rodents after feeding by Ld chiggers carrying Karp and Gilliam genotypes. The current findings reveal a complex association among the host, pathogen, and vector. PMID:24297814

  8. Bartonella henselae infections in an owner and two Papillon dogs exposed to tropical rat mites (Ornithonyssus bacoti).

    PubMed

    Bradley, Julie M; Mascarelli, Patricia E; Trull, Chelsea L; Maggi, Ricardo G; Breitschwerdt, Edward B

    2014-10-01

    After raccoons were trapped and removed from under a house in New York, the owner and her two Papillon dogs became infested with numerous rat mites (Ornithonyssus bacoti). Two weeks later, both dogs developed pruritus, progressively severe vesicular lesions, focal areas of skin exfoliation, swelling of the vulva or prepuce, abdominal pain, and behavioral changes. Two months after the mite infestation, the owner was hospitalized because of lethargy, fatigue, uncontrollable panic attacks, depression, headaches, chills, swollen neck lymph nodes, and vesicular lesions at the mite bite sites. Due to ongoing illness, 3 months after the mite infestation, alcohol-stored mites and blood and serum from both dogs and the owner were submitted for Bartonella serology and Bartonella alpha Proteobacteria growth medium (BAPGM) enrichment blood culture/PCR. Bartonella henselae DNA was amplified and sequenced from blood or culture specimens derived from both dogs, the owner, and pooled rat mites. Following repeated treatments with doxycycline, both dogs eventually became B. henselae seronegative and blood culture negative and clinical signs resolved. In contrast, the woman was never B. henselae seroreactive, but was again PCR positive for B. henselae 20 months after the mite infestation, despite prior treatment with doxycycline. Clinicians and vector biologists should consider the possibility that rat mites may play a role in Bartonella spp. transmission.

  9. Bartonella henselae infections in an owner and two Papillon dogs exposed to tropical rat mites (Ornithonyssus bacoti).

    PubMed

    Bradley, Julie M; Mascarelli, Patricia E; Trull, Chelsea L; Maggi, Ricardo G; Breitschwerdt, Edward B

    2014-10-01

    After raccoons were trapped and removed from under a house in New York, the owner and her two Papillon dogs became infested with numerous rat mites (Ornithonyssus bacoti). Two weeks later, both dogs developed pruritus, progressively severe vesicular lesions, focal areas of skin exfoliation, swelling of the vulva or prepuce, abdominal pain, and behavioral changes. Two months after the mite infestation, the owner was hospitalized because of lethargy, fatigue, uncontrollable panic attacks, depression, headaches, chills, swollen neck lymph nodes, and vesicular lesions at the mite bite sites. Due to ongoing illness, 3 months after the mite infestation, alcohol-stored mites and blood and serum from both dogs and the owner were submitted for Bartonella serology and Bartonella alpha Proteobacteria growth medium (BAPGM) enrichment blood culture/PCR. Bartonella henselae DNA was amplified and sequenced from blood or culture specimens derived from both dogs, the owner, and pooled rat mites. Following repeated treatments with doxycycline, both dogs eventually became B. henselae seronegative and blood culture negative and clinical signs resolved. In contrast, the woman was never B. henselae seroreactive, but was again PCR positive for B. henselae 20 months after the mite infestation, despite prior treatment with doxycycline. Clinicians and vector biologists should consider the possibility that rat mites may play a role in Bartonella spp. transmission. PMID:25325313

  10. Immunogene and viral transcript dynamics during parasitic Varroa destructor mite infection of developing honey bee (Apis mellifera) pupae.

    PubMed

    Kuster, Ryan D; Boncristiani, Humberto F; Rueppell, Olav

    2014-05-15

    The ectoparasitic Varroa destructor mite is a major contributor to the ongoing honey bee health crisis. Varroa interacts with honey bee viruses, exacerbating their pathogenicity. In addition to vectoring viruses, immunosuppression of the developing honey bee hosts by Varroa has been proposed to explain the synergy between viruses and mites. However, the evidence for honey bee immune suppression by V. destructor is contentious. We systematically studied the quantitative effects of experimentally introduced V. destructor mites on immune gene expression at five specific time points during the development of the honey bee hosts. Mites reproduced normally and were associated with increased titers of deformed wing virus in the developing bees. Our data on different immune genes show little evidence for immunosuppression of honey bees by V. destructor. Experimental wounding of developing bees increases relative immune gene expression and deformed wing virus titers. Combined, these results suggest that mite feeding activity itself and not immunosuppression may contribute to the synergy between viruses and mites. However, our results also suggest that increased expression of honey bee immune genes decreases mite reproductive success, which may be explored to enhance mite control strategies. Finally, our expression data for multiple immune genes across developmental time and different experimental treatments indicates co-regulation of several of these genes and thus improves our understanding of the understudied honey bee immune system.

  11. HIV infection in the etiology of lung cancer: confounding, causality, and consequences.

    PubMed

    Kirk, Gregory D; Merlo, Christian A

    2011-06-01

    Persons infected with HIV have an elevated risk of lung cancer, but whether the increase simply reflects a higher smoking prevalence continues to be debated. This review summarizes existing data on the association of HIV infection and lung cancer, with particular attention to study design and adjustment for cigarette smoking. Potential mechanisms by which HIV infection may lead to lung cancer are discussed. Finally, irrespective of causality and mechanisms, lung cancer represents an important and growing problem confronting HIV-infected patients and their providers. Substantial efforts are needed to promote smoking cessation and to control lung cancer among HIV-infected populations.

  12. [Nocardia farcinica lung infection in a patient with cystic fibrosis and a lung transplant].

    PubMed

    Chacón, C F; Vicente, R; Ramos, F; Porta, J; Lopez Maldonado, A; Ansotegui, E

    2015-03-01

    Patients with cystic fibrosis have a higher risk of developing chronic respiratory infectious diseases. The Nocardia farcinica lung infection is rare in this group of patients, and there are limited publications about this topic. Its diagnosis is complex, due to the clinical and the radiology signs being non-specific. Identification of the agent responsible in the sputum culture is occasionally negative. It is a slow growing organism and for this reason treatment is delayed, which can lead to an increase in complications, hospitable stays, and mortality. A case is reported on a 26 year-old woman with cystic fibrosis and chronic lung colonization by Nocardia farcinica and Aspergillus fumigatus, on long-term treatment with ciprofloxacin, trimethoprim-sulfamethoxazole, and posaconazole, who was admitted to ICU after bilateral lung transplantation. The initial post-operative progress was satisfactory. After discharge, the patient showed a gradual respiratory insufficiency with new chest X-ray showing diffuse infiltrates. Initially, the agent was not seen in the sputum culture. Prompt and aggressive measures were taken, due to the high clinical suspicion of a Nocardia farcinica lung infection. Treatment with a combination of amikacin and meropenem, and later combined with linezolid, led to the disappearance of the lung infiltrates and a clinical improvement. In our case, we confirm the rapid introduction of Nocardia farcinica in the new lungs. The complex identification and the delay in treatment increased the morbimortality. There is a special need for its eradication in patients with lung transplant, due to the strong immunosuppressive treatment. PMID:25443661

  13. Lung Microbiota Changes Associated with Chronic Pseudomonas aeruginosa Lung Infection and the Impact of Intravenous Colistimethate Sodium

    PubMed Central

    Collie, David; Glendinning, Laura; Govan, John; Wright, Steven; Thornton, Elisabeth; Tennant, Peter; Doherty, Catherine; McLachlan, Gerry

    2015-01-01

    Background Exacerbations associated with chronic lung infection with Pseudomonas aeruginosa are a major contributor to morbidity, mortality and premature death in cystic fibrosis. Such exacerbations are treated with antibiotics, which generally lead to an improvement in lung function and reduced sputum P. aeruginosa density. This potentially suggests a role for the latter in the pathogenesis of exacerbations. However, other data suggesting that changes in P. aeruginosa sputum culture status may not reliably predict an improvement in clinical status, and data indicating no significant changes in either total bacterial counts or in P. aeruginosa numbers in sputum samples collected prior to pulmonary exacerbation sheds doubt on this assumption. We used our recently developed lung segmental model of chronic Pseudomonas infection in sheep to investigate the lung microbiota changes associated with chronic P. aeruginosa lung infection and the impact of systemic therapy with colistimethate sodium (CMS). Methodology/Principal Findings We collected protected specimen brush (PSB) samples from sheep (n = 8) both prior to and 14 days after establishment of chronic local lung infection with P aeruginosa. Samples were taken from both directly infected lung segments (direct) and segments spatially remote to such sites (remote). Four sheep were treated with daily intravenous injections of CMS between days 7 and 14, and four were treated with a placebo. Necropsy examination at d14 confirmed the presence of chronic local lung infection and lung pathology in every direct lung segment. The predominant orders in lung microbiota communities before infection were Bacillales, Actinomycetales and Clostridiales. While lung microbiota samples were more likely to share similarities with other samples derived from the same lung, considerable within- and between-animal heterogeneity could be appreciated. Pseudomonadales joined the aforementioned list of predominant orders in lung microbiota

  14. MUC18 Regulates Lung Rhinovirus Infection and Inflammation

    PubMed Central

    Berman, Reena; Jiang, Di; Wu, Qun; Stevenson, Connor R.; Schaefer, Niccolette R.; Chu, Hong Wei

    2016-01-01

    Background MUC18 is upregulated in the lungs of asthma and COPD patients. It has been shown to have pro-inflammatory functions in cultured human airway epithelial cells during viral infections and in mice during lung bacterial infections. However, the in vivo role of MUC18 in the context of viral infections remains poorly understood. The goal of this study is to define the in vivo function of MUC18 during respiratory rhinovirus infection. Methods Muc18 wild-type (WT) and knockout (KO) mice were infected with human rhinovirus 1B (HRV-1B) and sacrificed after 1 day to determine the inflammatory and antiviral responses. To examine the direct effects of Muc18 on viral infection, tracheal epithelial cells isolated from WT and KO mice were grown under air-liquid interface and infected with HRV-1B. Finally, siRNA mediated knockdown of MUC18 was performed in human airway epithelial cells (AECs) to define the impact of MUC18 on human airway response to HRV-1B. Results Both viral load and neutrophilic inflammation were significantly decreased in Muc18 KO mice compared to WT mice. In the in vitro setting, viral load was significantly lower and antiviral gene expression was higher in airway epithelial cells of Muc18 KO mice than the WT mice. Furthermore, in MUC18 knockdown human AECs, viral load was decreased and antiviral gene expression was increased compared to controls. Conclusions Our study is the first to demonstrate MUC18’s pro-inflammatory and pro-viral function in an in vivo mouse model of rhinovirus infection. PMID:27701461

  15. Stochastic Tracking of Infection in a CF Lung

    PubMed Central

    Zarei, Sara; Mirtar, Ali; Rohwer, Forest; Salamon, Peter

    2014-01-01

    Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) scan are the two ubiquitous imaging sources that physicians use to diagnose patients with Cystic Fibrosis (CF) or any other Chronic Obstructive Pulmonary Disease (COPD). Unfortunately the cost constraints limit the frequent usage of these medical imaging procedures. In addition, even though both CT scan and MRI provide mesoscopic details of a lung, in order to obtain microscopic information a very high resolution is required. Neither MRI nor CT scans provide micro level information about the location of infection in a binary tree structure the binary tree structure of the human lung. In this paper we present an algorithm that enhances the current imaging results by providing estimated micro level information concerning the location of the infection. The estimate is based on a calculation of the distribution of possible mucus blockages consistent with available information using an offline Metropolis-Hastings algorithm in combination with a real-time interpolation scheme. When supplemented with growth rates for the pockets of mucus, the algorithm can also be used to estimate how lung functionality as manifested in spirometric tests will change in patients with CF or COPD. PMID:25360611

  16. Modeling Granulomas in Response to Infection in the Lung.

    PubMed

    Hao, Wenrui; Schlesinger, Larry S; Friedman, Avner

    2016-01-01

    Alveolar macrophages play a large role in the innate immune response of the lung. However, when these highly immune-regulatory cells are unable to eradicate pathogens, the adaptive immune system, which includes activated macrophages and lymphocytes, particularly T cells, is called upon to control the pathogens. This collection of immune cells surrounds, isolates and quarantines the pathogen, forming a small tissue structure called a granuloma for intracellular pathogens like Mycobacterium tuberculosis (Mtb). In the present work we develop a mathematical model of the dynamics of a granuloma by a system of partial differential equations. The 'strength' of the adaptive immune response to infection in the lung is represented by a parameter α, the flux rate by which T cells and M1 macrophages that immigrated from the lymph nodes enter into the granuloma through its boundary. The parameter α is negatively correlated with the 'switching time', namely, the time it takes for the number of M1 type macrophages to surpass the number of infected, M2 type alveolar macrophages. Simulations of the model show that as α increases the radius of the granuloma and bacterial load in the granuloma both decrease. The model is used to determine the efficacy of potential host-directed therapies in terms of the parameter α, suggesting that, with fixed dosing level, an infected individual with a stronger immune response will receive greater benefits in terms of reducing the bacterial load. PMID:26986986

  17. Modeling Granulomas in Response to Infection in the Lung

    PubMed Central

    Hao, Wenrui; Schlesinger, Larry S.; Friedman, Avner

    2016-01-01

    Alveolar macrophages play a large role in the innate immune response of the lung. However, when these highly immune-regulatory cells are unable to eradicate pathogens, the adaptive immune system, which includes activated macrophages and lymphocytes, particularly T cells, is called upon to control the pathogens. This collection of immune cells surrounds, isolates and quarantines the pathogen, forming a small tissue structure called a granuloma for intracellular pathogens like Mycobacterium tuberculosis (Mtb). In the present work we develop a mathematical model of the dynamics of a granuloma by a system of partial differential equations. The ‘strength’ of the adaptive immune response to infection in the lung is represented by a parameter α, the flux rate by which T cells and M1 macrophages that immigrated from the lymph nodes enter into the granuloma through its boundary. The parameter α is negatively correlated with the ‘switching time’, namely, the time it takes for the number of M1 type macrophages to surpass the number of infected, M2 type alveolar macrophages. Simulations of the model show that as α increases the radius of the granuloma and bacterial load in the granuloma both decrease. The model is used to determine the efficacy of potential host-directed therapies in terms of the parameter α, suggesting that, with fixed dosing level, an infected individual with a stronger immune response will receive greater benefits in terms of reducing the bacterial load. PMID:26986986

  18. Alveolar Macrophages Are a Prominent but Nonessential Target for Murine Cytomegalovirus Infecting the Lungs

    PubMed Central

    Farrell, Helen E.; Lawler, Clara; Oliveira, Martha T.; Davis-Poynter, Nick

    2015-01-01

    ABSTRACT Cytomegaloviruses (CMVs) infect the lungs and cause pathological damage there in immunocompromised hosts. How lung infection starts is unknown. Inhaled murine CMV (MCMV) directly infected alveolar macrophages (AMs) and type 2 alveolar epithelial cells (AEC2s) but not type 1 alveolar epithelial cells (AEC1s). In contrast, herpes simplex virus 1 infected AEC1s and murid herpesvirus 4 (MuHV-4) infected AEC1s via AMs. MCMV-infected AMs prominently expressed viral reporter genes from a human CMV IE1 promoter; but most IE1-positive cells were AEC2s, and CD11c-cre mice, which express cre in AMs, switched the fluorochrome expression of <5% of floxed MCMV in the lungs. In contrast, CD11C-cre mice exhibited fluorochrome switching in >90% of floxed MuHV-4 in the lungs and 50% of floxed MCMV in the blood. AM depletion increased MCMV titers in the lung during the acute phase of infection. Thus, the influence of AMs was more restrictive than permissive. Circulating monocytes entered infected lungs in large numbers and became infected, but not directly; infection occurred mainly via AEC2s. Mice infected with an MCMV mutant lacking its m131/m129 chemokine homolog, which promotes macrophage infection, showed levels of lung infection equivalent to those of wild-type MCMV-infected mice. The level of lung infiltration by Gr-1-positive cells infected with the MCMV m131/m129-null mutant was modestly different from that for wild-type MCMV-infected lungs. These results are consistent with myeloid cells mainly disseminating MCMV from the lungs, whereas AEC2s provide local amplification. IMPORTANCE Cytomegaloviruses (CMVs) chronically and systemically infect most mammals. Human CMV infection is usually asymptomatic but causes lung disease in people with poor immune function. As human infection is hard to analyze, studies with related animal viruses provide important insights. We show that murine CMV has two targets in the lungs: macrophages and surfactant-secreting epithelial cells

  19. Staphylococcus aureus α toxin potentiates opportunistic bacterial lung infections.

    PubMed

    Cohen, Taylor S; Hilliard, Jamese J; Jones-Nelson, Omari; Keller, Ashley E; O'Day, Terrence; Tkaczyk, Christine; DiGiandomenico, Antonio; Hamilton, Melissa; Pelletier, Mark; Wang, Qun; Diep, Binh An; Le, Vien T M; Cheng, Lily; Suzich, JoAnn; Stover, C Kendall; Sellman, Bret R

    2016-03-01

    Broad-spectrum antibiotic use may adversely affect a patient's beneficial microbiome and fuel cross-species spread of drug resistance. Although alternative pathogen-specific approaches are rationally justified, a major concern for this precision medicine strategy is that co-colonizing or co-infecting opportunistic bacteria may still cause serious disease. In a mixed-pathogen lung infection model, we find that the Staphylococcus aureus virulence factor α toxin potentiates Gram-negative bacterial proliferation, systemic spread, and lethality by preventing acidification of bacteria-containing macrophage phagosomes, thereby reducing effective killing of both S. aureus and Gram-negative bacteria. Prophylaxis or early treatment with a single α toxin neutralizing monoclonal antibody prevented proliferation of co-infecting Gram-negative pathogens and lethality while also promoting S. aureus clearance. These studies suggest that some pathogen-specific, antibody-based approaches may also work to reduce infection risk in patients colonized or co-infected with S. aureus and disparate drug-resistant Gram-negative bacterial opportunists.

  20. Staphylococcus aureus α toxin potentiates opportunistic bacterial lung infections.

    PubMed

    Cohen, Taylor S; Hilliard, Jamese J; Jones-Nelson, Omari; Keller, Ashley E; O'Day, Terrence; Tkaczyk, Christine; DiGiandomenico, Antonio; Hamilton, Melissa; Pelletier, Mark; Wang, Qun; Diep, Binh An; Le, Vien T M; Cheng, Lily; Suzich, JoAnn; Stover, C Kendall; Sellman, Bret R

    2016-03-01

    Broad-spectrum antibiotic use may adversely affect a patient's beneficial microbiome and fuel cross-species spread of drug resistance. Although alternative pathogen-specific approaches are rationally justified, a major concern for this precision medicine strategy is that co-colonizing or co-infecting opportunistic bacteria may still cause serious disease. In a mixed-pathogen lung infection model, we find that the Staphylococcus aureus virulence factor α toxin potentiates Gram-negative bacterial proliferation, systemic spread, and lethality by preventing acidification of bacteria-containing macrophage phagosomes, thereby reducing effective killing of both S. aureus and Gram-negative bacteria. Prophylaxis or early treatment with a single α toxin neutralizing monoclonal antibody prevented proliferation of co-infecting Gram-negative pathogens and lethality while also promoting S. aureus clearance. These studies suggest that some pathogen-specific, antibody-based approaches may also work to reduce infection risk in patients colonized or co-infected with S. aureus and disparate drug-resistant Gram-negative bacterial opportunists. PMID:26962155

  1. Lung epithelial NOX/DUOX and respiratory virus infections.

    PubMed

    Grandvaux, Nathalie; Mariani, Mélissa; Fink, Karin

    2015-03-01

    Determining the role of NADPH oxidases in the context of virus infection is an emerging area of research and our knowledge is still sparse. The expression of various isoforms of NOX/DUOX (NADPH oxidase/dual oxidase) in the epithelial cells (ECs) lining the respiratory tract renders them primary sites from which to orchestrate the host defence against respiratory viruses. Accumulating evidence reveals distinct facets of the involvement of NOX/DUOX in host antiviral and pro-inflammatory responses and in the control of the epithelial barrier integrity, with individual isoforms mediating co-operative, but surprisingly also opposing, functions. Although in vivo studies in mice are in line with some of these observations, a complete understanding of the specific functions of epithelial NOX/DUOX awaits lung epithelial-specific conditional knockout mice. The goal of the present review is to summarize our current knowledge of the role of individual NOX/DUOX isoforms expressed in the lung epithelium in the context of respiratory virus infections so as to highlight potential opportunities for therapeutic intervention.

  2. Vaccination with recombinant actin from scab mites and evaluation of its protective efficacy against Psoroptes cuniculi infection.

    PubMed

    Zheng, W; Tang, Q; Zhang, R; Jise, Q; Ren, Y; Nong, X; Wu, X; Gu, X; Wang, S; Peng, X; Lai, S; Yang, G

    2013-02-01

    The mite Psoroptes cuniculi is globally widespread and has a serious impact on commercial rabbit breeding. Current treatment methods are based on chemotherapy. Because of the disadvantages of these methods, alternative measures are required, and vaccination is one of the most promising strategies. Here, we cloned and expressed the recombinant P. cuniculi actin gene (rPc-act). Antiserum levels against rPc-act in rabbits were used to locate actin distribution in mite sections. Challenge trials were carried out to evaluate the immunity protection of rPc-act in rabbits, with antibody levels determined by ELISA. Sequence analysis of this gene fragment showed 89·26% and 84·91% identity to Sarcoptes scabiei and Mayetiola destructor sequences, respectively. Immunohistochemistry showed rPc-act to locate widely throughout the mites, especially in feet and muscle tissues. Recombinant P. cuniculi actin with QuliA adjuvant was used to immunize six rabbits. Each animal was challenge-infested with 25-50 adult mites. Although IgE levels showed no significant difference to controls, IgG levels were significantly higher, and clinical development showed no significantly different severity of lesions in vaccinated rabbits than in the controls. This study showed that rPc-act is a muscular isotype actin and has no clinical protective efficacy against P. cuniculi. PMID:23078134

  3. ICAM-1-dependent and ICAM-1-independent neutrophil lung infiltration by porcine reproductive and respiratory syndrome virus infection.

    PubMed

    Liu, Jie; Hou, Make; Yan, Meiping; Lü, Xinhui; Gu, Wei; Zhang, Songlin; Gao, Jianfeng; Liu, Bang; Wu, Xiaoxiong; Liu, Guoquan

    2015-08-01

    Neutrophils are innate immune cells that play a crucial role in the first line of host defense. It is also known that neutrophil lung recruitment and infiltration may cause lung injury. The roles of neutrophils in virus infection-induced lung injury are not clear. We explore the mechanisms of neutrophil lung infiltration and the potential biomarkers for lung injury in a swine model of lung injury caused by natural or experimental porcine reproductive and respiratory syndrome virus (PRRSV) infection. Neutrophil lung infiltration was determined by measurement of myeloperoxidase expression and enzyme activity of lung tissues. Myeloperoxidase expression and enzyme activity were dramatically increased in the naturally and experimentally infected lung tissues. Chemokine analysis by quantitative PCR and ELISA showed that IL-8 expression was increased in both infections, while monocyte chemoattractant protein-1 expression was increased only in experimentally infected lung tissues. Expression of the cell adhesion molecules VCAM-1 and ICAM-1 was measured by quantitative PCR and Western blotting. VCAM-1 expression was increased in experimentally and naturally infected lungs, whereas ICAM-1 expression was increased only in the naturally infected lung samples. Our results suggest that neutrophil lung infiltrations in the infected animals are both ICAM-1- and -independent and that combined expression of VCAM-1 and IL-8 may serve as the biomarker for lung injury induced by virus infection.

  4. Influenza Virus Infection Induces Platelet-Endothelial Adhesion Which Contributes to Lung Injury.

    PubMed

    Sugiyama, Michael G; Gamage, Asela; Zyla, Roman; Armstrong, Susan M; Advani, Suzanne; Advani, Andrew; Wang, Changsen; Lee, Warren L

    2016-02-01

    Lung injury after influenza infection is characterized by increased permeability of the lung microvasculature, culminating in acute respiratory failure. Platelets interact with activated endothelial cells and have been implicated in the pathogenesis of some forms of acute lung injury. Autopsy studies have revealed pulmonary microthrombi after influenza infection, and epidemiological studies suggest that influenza vaccination is protective against pulmonary thromboembolism; however, the effect of influenza infection on platelet-endothelial interactions is unclear. We demonstrate that endothelial infection with both laboratory and clinical strains of influenza virus increased the adhesion of human platelets to primary human lung microvascular endothelial cells. Platelets adhered to infected cells as well as to neighboring cells, suggesting a paracrine effect. Influenza infection caused the upregulation of von Willebrand factor and ICAM-1, but blocking these receptors did not prevent platelet-endothelial adhesion. Instead, platelet adhesion was inhibited by both RGDS peptide and a blocking antibody to platelet integrin α5β1, implicating endothelial fibronectin. Concordantly, lung histology from infected mice revealed viral dose-dependent colocalization of viral nucleoprotein and the endothelial marker PECAM-1, while platelet adhesion and fibronectin deposition also were observed in the lungs of influenza-infected mice. Inhibition of platelets using acetylsalicylic acid significantly improved survival, a finding confirmed using a second antiplatelet agent. Thus, influenza infection induces platelet-lung endothelial adhesion via fibronectin, contributing to mortality from acute lung injury. The inhibition of platelets may constitute a practical adjunctive strategy to the treatment of severe infections with influenza.IMPORTANCE There is growing appreciation of the involvement of the lung endothelium in the pathogenesis of severe infections with influenza virus. We have

  5. Influenza Virus Infection Induces Platelet-Endothelial Adhesion Which Contributes to Lung Injury.

    PubMed

    Sugiyama, Michael G; Gamage, Asela; Zyla, Roman; Armstrong, Susan M; Advani, Suzanne; Advani, Andrew; Wang, Changsen; Lee, Warren L

    2015-12-04

    Lung injury after influenza infection is characterized by increased permeability of the lung microvasculature, culminating in acute respiratory failure. Platelets interact with activated endothelial cells and have been implicated in the pathogenesis of some forms of acute lung injury. Autopsy studies have revealed pulmonary microthrombi after influenza infection, and epidemiological studies suggest that influenza vaccination is protective against pulmonary thromboembolism; however, the effect of influenza infection on platelet-endothelial interactions is unclear. We demonstrate that endothelial infection with both laboratory and clinical strains of influenza virus increased the adhesion of human platelets to primary human lung microvascular endothelial cells. Platelets adhered to infected cells as well as to neighboring cells, suggesting a paracrine effect. Influenza infection caused the upregulation of von Willebrand factor and ICAM-1, but blocking these receptors did not prevent platelet-endothelial adhesion. Instead, platelet adhesion was inhibited by both RGDS peptide and a blocking antibody to platelet integrin α5β1, implicating endothelial fibronectin. Concordantly, lung histology from infected mice revealed viral dose-dependent colocalization of viral nucleoprotein and the endothelial marker PECAM-1, while platelet adhesion and fibronectin deposition also were observed in the lungs of influenza-infected mice. Inhibition of platelets using acetylsalicylic acid significantly improved survival, a finding confirmed using a second antiplatelet agent. Thus, influenza infection induces platelet-lung endothelial adhesion via fibronectin, contributing to mortality from acute lung injury. The inhibition of platelets may constitute a practical adjunctive strategy to the treatment of severe infections with influenza.IMPORTANCE There is growing appreciation of the involvement of the lung endothelium in the pathogenesis of severe infections with influenza virus. We have

  6. Complete Remission of Minimal Change Disease Following an Improvement of Lung Mycobacterium avium Infection.

    PubMed

    Yamashiro, Aoi; Uchida, Takahiro; Ito, Seigo; Oshima, Naoki; Oda, Takashi; Kumagai, Hiroo

    2016-01-01

    A 46-year-old woman suddenly developed peripheral edema. Her massive proteinuria, hypoproteinemia, and renal biopsy findings yielded the diagnosis of minimal change disease (MCD). In addition, lung Mycobacterium avium infection was diagnosed according to a positive culture of her bronchoalveolar lavage fluid. The lung lesion was improved by anti-nontuberculous mycobacteria therapy. Surprisingly, her proteinuria also gradually decreased and she attained complete remission of MCD without any immunosuppressive therapy. She has subsequently remained in complete remission. We herein report an interesting case of MCD with lung Mycobacterium avium infection, suggesting a causal relationship among infection, immune system abnormality, and MCD/nephrotic syndrome.

  7. Complete Remission of Minimal Change Disease Following an Improvement of Lung Mycobacterium avium Infection.

    PubMed

    Yamashiro, Aoi; Uchida, Takahiro; Ito, Seigo; Oshima, Naoki; Oda, Takashi; Kumagai, Hiroo

    2016-01-01

    A 46-year-old woman suddenly developed peripheral edema. Her massive proteinuria, hypoproteinemia, and renal biopsy findings yielded the diagnosis of minimal change disease (MCD). In addition, lung Mycobacterium avium infection was diagnosed according to a positive culture of her bronchoalveolar lavage fluid. The lung lesion was improved by anti-nontuberculous mycobacteria therapy. Surprisingly, her proteinuria also gradually decreased and she attained complete remission of MCD without any immunosuppressive therapy. She has subsequently remained in complete remission. We herein report an interesting case of MCD with lung Mycobacterium avium infection, suggesting a causal relationship among infection, immune system abnormality, and MCD/nephrotic syndrome. PMID:27629965

  8. Multiple Infections with Cardinium and Two Strains of Wolbachia in The Spider Mite Tetranychus phaselus Ehara: Revealing New Forces Driving the Spread of Wolbachia

    PubMed Central

    Zhao, Dong-Xiao; Chen, Da-Song; Ge, Cheng; Gotoh, Tetsuo; Hong, Xiao-Yue

    2013-01-01

    Cytoplasmic incompatibility (CI) has been proposed as a major mechanism by which certain strains of Wolbachia to invade and persist in host populations. However, mechanisms that underlie the invasion and persistence of non-CI strains are less well understood. Here, we established a spider mite Tetranychus phaselus population multiply infected by Cardinium as well as two distinct lineages of Wolbachia, designated wCon and wOri, to study the forces driving the spread of the non-CI strain of Wolbachia wOri. Interestingly, we found that wOri provided a longevity advantage to its female hosts under ideal conditions, making wOri stay longer in this population, and then being transmitted to more offspring. Furthermore, the lifespan of uninfected females was reduced when mated with multiple-infected males. As a result, the uninfected population is attenuated by the multiple-infected males. Thus, we infer that the host age effects of multiple infection may represent sufficient forces driving the spread of wOri through the host population. PMID:23355904

  9. Pseudomonas aeruginosa Diversification during Infection Development in Cystic Fibrosis Lungs-A Review.

    PubMed

    Sousa, Ana Margarida; Pereira, Maria Olívia

    2014-01-01

    Pseudomonas aeruginosa is the most prevalent pathogen of cystic fibrosis (CF) lung disease. Its long persistence in CF airways is associated with sophisticated mechanisms of adaptation, including biofilm formation, resistance to antibiotics, hypermutability and customized pathogenicity in which virulence factors are expressed according the infection stage. CF adaptation is triggered by high selective pressure of inflamed CF lungs and by antibiotic treatments. Bacteria undergo genetic, phenotypic, and physiological variations that are fastened by the repeating interplay of mutation and selection. During CF infection development, P. aeruginosa gradually shifts from an acute virulent pathogen of early infection to a host-adapted pathogen of chronic infection. This paper reviews the most common changes undergone by P. aeruginosa at each stage of infection development in CF lungs. The comprehensive understanding of the adaptation process of P. aeruginosa may help to design more effective antimicrobial treatments and to identify new targets for future drugs to prevent the progression of infection to chronic stages. PMID:25438018

  10. Lung cancer in HIV-infected patients in the combination antiretroviral treatment era

    PubMed Central

    Moltó, José; Sirera, Guillem; Clotet, Bonaventura

    2015-01-01

    The advent of combination antiretroviral treatment (cART) has been followed by a decrease in HIV-associated morbidity and mortality, but also by an apparent increase in the incidence of non-AIDS-defining cancers (NADCs). The risk of lung cancer is substantially higher in HIV-infected patients than in the general population, in part due to aging and tobacco use, and it is the most frequent NADC. The management of lung cancer in HIV-infected patients has some peculiarities that need to be taken into account. This review focuses on the epidemiology, risk factors, and clinical management of lung cancer in HIV-infected patients. In addition, screening tools and future perspectives are also discussed. Keywords Lung cancer; non-AIDS-defining cancers (NADCs); HIV infection; antiretroviral treatment PMID:26798577

  11. Chlamydial Lung Infection Induces Transient IL-9 Production Which Is Redundant for Host Defense against Primary Infection

    PubMed Central

    Peng, Ying; Gao, Xiaoling; Yang, Jie; Shekhar, Sudhanshu; Wang, Shuhe; Fan, Yijun; Yang, Xi

    2015-01-01

    IL-9/Th9 responses are recently found to be important for innate and adaptive immunity particularly in parasitic infections. To date, the study on the role of IL-9 in bacterial infections is limited and the reported data are contradictory. One reported function of IL-9/Th9 is to modulate Th1/Th17 responses. Since our and others’ previous work has shown a critical role of Th1 and Th17 cells in host defense against chlamydial lung infection, we here examined the role of IL-9 responses in Chlamydia muridarum (Cm) lung infection, particularly its effect on Th1 and Th17 responses and outcome infection. Our data showed quick but transient IL-9 production in the lung following infection, peaking at day 3 and back to baseline around day 7. CD4+ T cell was the major source of IL-9 production in the lung infection. Blockade of endogenous IL-9 using neutralizing antibody failed to change Interferon-γ (IFN-γ) and IL-17 production by cultured spleen mononuclear cells isolated from Cm infected mice. Similarly, in vivo neutralization of IL-9 failed to show significant effect on T cell (Th1 and Th17) and antibody responses (IgA, IgG1 and IgG2a). Consistently, the neutralization of IL-9 had no significant effect on disease process, including body weight change, bacterial burden and histopathological score. The data suggest that IL-9 production following chlamydial lung infection is redundant for host defense against the intracellular bacteria. PMID:25646821

  12. The balance between protective and pathogenic immune responses in the TB-infected lung.

    PubMed

    Orme, Ian M; Robinson, Richard T; Cooper, Andrea M

    2015-01-01

    Tuberculosis is a disease of the lung, and efficient transmission is dependent on the generation of a lesion in the lung, which results in a bacterium-laden cough. Mycobacterium tuberculosis (Mtb) is able to manipulate both the innate and acquired immune response of the host. This manipulation results in an effective CD4(+) T cell response that limits disease throughout the body but can also promote the development of progressively destructive lesions in the lung. In this way Mtb infection can result in an ambulatory individual who has a lesion in the lung capable of transmitting Mtb. The inflammatory environment within the lung lesion is manipulated by Mtb throughout infection and can limit the expression of acquired immunity by a variety of pathways.

  13. Role of small colony variants in persistence of Pseudomonas aeruginosa infections in cystic fibrosis lungs

    PubMed Central

    Malone, Jacob G

    2015-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen that predominates during the later stages of cystic fibrosis (CF) lung infections. Over many years of chronic lung colonization, P. aeruginosa undergoes extensive adaptation to the lung environment, evolving both toward a persistent, low virulence state and simultaneously diversifying to produce a number of phenotypically distinct morphs. These lung-adapted P. aeruginosa strains include the small colony variants (SCVs), small, autoaggregative isolates that show enhanced biofilm formation, strong attachment to surfaces, and increased production of exopolysaccharides. Their appearance in the sputum of CF patients correlates with increased resistance to antibiotics, poor lung function, and prolonged persistence of infection, increasing their relevance as a subject for clinical investigation. The evolution of SCVs in the CF lung is associated with overproduction of the ubiquitous bacterial signaling molecule cyclic-di-GMP, with increased cyclic-di-GMP levels shown to be responsible for the SCV phenotype in a number of different CF lung isolates. Here, we review the current state of research in clinical P. aeruginosa SCVs. We will discuss the phenotypic characteristics underpinning the SCV morphotype, the clinical implications of lung colonization with SCVs, and the molecular basis and clinical evolution of the SCV phenotype in the CF lung environment. PMID:26251621

  14. ImmunoPET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo

    PubMed Central

    Rolle, Anna-Maria; Hasenberg, Mike; Thornton, Christopher R.; Solouk-Saran, Djamschid; Männ, Linda; Weski, Juliane; Maurer, Andreas; Fischer, Eliane; Spycher, Philipp R.; Schibli, Roger; Boschetti, Frederic; Stegemann-Koniszewski, Sabine; Bruder, Dunja; Severin, Gregory W.; Autenrieth, Stella E.; Krappmann, Sven; Davies, Genna; Pichler, Bernd J.; Gunzer, Matthias; Wiehr, Stefan

    2016-01-01

    Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease caused by the fungus Aspergillus fumigatus, and is a leading cause of invasive fungal infection-related mortality and morbidity in patients with hematological malignancies and bone marrow transplants. We developed and tested a novel probe for noninvasive detection of A. fumigatus lung infection based on antibody-guided positron emission tomography and magnetic resonance (immunoPET/MR) imaging. Administration of a [64Cu]DOTA-labeled A. fumigatus-specific monoclonal antibody (mAb), JF5, to neutrophil-depleted A. fumigatus-infected mice allowed specific localization of lung infection when combined with PET. Optical imaging with a fluorochrome-labeled version of the mAb showed colocalization with invasive hyphae. The mAb-based newly developed PET tracer [64Cu]DOTA-JF5 distinguished IPA from bacterial lung infections and, in contrast to [18F]FDG-PET, discriminated IPA from a general increase in metabolic activity associated with lung inflammation. To our knowledge, this is the first time that antibody-guided in vivo imaging has been used for noninvasive diagnosis of a fungal lung disease (IPA) of humans, an approach with enormous potential for diagnosis of infectious diseases and with potential for clinical translation. PMID:26787852

  15. ImmunoPET/MR imaging allows specific detection of Aspergillus fumigatus lung infection in vivo.

    PubMed

    Rolle, Anna-Maria; Hasenberg, Mike; Thornton, Christopher R; Solouk-Saran, Djamschid; Männ, Linda; Weski, Juliane; Maurer, Andreas; Fischer, Eliane; Spycher, Philipp R; Schibli, Roger; Boschetti, Frederic; Stegemann-Koniszewski, Sabine; Bruder, Dunja; Severin, Gregory W; Autenrieth, Stella E; Krappmann, Sven; Davies, Genna; Pichler, Bernd J; Gunzer, Matthias; Wiehr, Stefan

    2016-02-23

    Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease caused by the fungus Aspergillus fumigatus, and is a leading cause of invasive fungal infection-related mortality and morbidity in patients with hematological malignancies and bone marrow transplants. We developed and tested a novel probe for noninvasive detection of A. fumigatus lung infection based on antibody-guided positron emission tomography and magnetic resonance (immunoPET/MR) imaging. Administration of a [(64)Cu]DOTA-labeled A. fumigatus-specific monoclonal antibody (mAb), JF5, to neutrophil-depleted A. fumigatus-infected mice allowed specific localization of lung infection when combined with PET. Optical imaging with a fluorochrome-labeled version of the mAb showed colocalization with invasive hyphae. The mAb-based newly developed PET tracer [(64)Cu]DOTA-JF5 distinguished IPA from bacterial lung infections and, in contrast to [(18)F]FDG-PET, discriminated IPA from a general increase in metabolic activity associated with lung inflammation. To our knowledge, this is the first time that antibody-guided in vivo imaging has been used for noninvasive diagnosis of a fungal lung disease (IPA) of humans, an approach with enormous potential for diagnosis of infectious diseases and with potential for clinical translation. PMID:26787852

  16. Activation of pulmonary and lymph node dendritic cells during chronic Pseudomonas aeruginosa lung infection in mice.

    PubMed

    Damlund, Dina Silke Malling; Christophersen, Lars; Jensen, Peter Østrup; Alhede, Morten; Høiby, Niels; Moser, Claus

    2016-06-01

    The majority of cystic fibrosis (CF) patients acquire chronic Pseudomonas aeruginosa lung infection, resulting in increased mortality and morbidity. The chronic P. aeruginosa lung infection is characterized by bacteria growing in biofilm surrounded by polymorphonuclear neutrophils (PMNs). However, the infection is not eradicated and the inflammatory response leads to gradual degradation of the lung tissue. In CF patients, a Th2-dominated adaptive immune response with a pronounced antibody response is correlated with poorer outcome. Dendritic cells (DCs) are crucial in bridging the innate immune system with the adaptive immune response. Once activated, the DCs deliver a set of signals to uncommitted T cells that induce development, such as expansion of regulatory T cells and polarization of Th1, Th2 or Th17 subsets. In this study, we characterized DCs in lungs and regional lymph nodes in BALB/c mice infected using intratracheal installation of P. aeruginosa embedded in seaweed alginate in the lungs. A significantly elevated concentration of DCs was detected earlier in the lungs than in the regional lymph nodes. To evaluate whether the chronic P. aeruginosa lung infection leads to activation of DCs, costimulatory molecules CD80 and CD86 were analyzed. During infection, the DCs showed significant elevation of CD80 and CD86 expression in both the lungs and the regional lymph nodes. Interestingly, the percentage of CD86-positive cells was significantly higher than the percentage of CD80-positive cells in the lymph nodes. In addition, cytokine production from Lipopolysaccharides (LPS)-stimulated DCs was analyzed demonstrating elevated production of IL-6, IL-10 and IL-12. However, production of IL-12 was suppressed earlier than IL-6 and IL-10. These results support that DCs are involved in skewing of the Th1/Th2 balance in CF and may be a possible treatment target. PMID:27009697

  17. The Dog Mite, Demodex canis: Prevalence, Fungal Co-Infection, Reactions to Light, and Hair Follicle Apoptosis

    PubMed Central

    Tsai, Yu-Jen; Chung, Wen-Cheng; Wang, Lian-Chen; Ju, Yu-Ten; Hong, Chin-Lin; Tsai, Yu-Yang; Li, Yi-Hung; Wu, Ying-Ling

    2011-01-01

    Infection rate, reaction to light, and hair follicle apoptosis are examined in the dogmite, Demodex canis Leydig (Prostigmata: Demodicidae), in dogs from the northern area of Taiwan. An analysis of relevant samples revealed 7.2% (73/1013) prevalence of D. canis infection. Infection during the investigation peaked each winter, with an average prevalence of 12.5% (32/255). The infection rates significantly varied in accordance with month, sex, age, and breed (p < 0.05). Most of the lesions were discovered on the backs of the infected animals, where the infection rate was 52.1% (38/73) (P < 0.05). The epidemiologic analysis of infection based on landscape area factor, found that employing a map-overlapping method showed a higher infection rate in the eastern distribution of Taiwan's northern area than other areas. Isolation tests for Microsporum canis Bodin (Onygenales: Arthrodermataceae) and Trichophyton mentagrophyte Robin (Blanchard) on the D. canis infected dogs revealed prevalence rates of 4.4% (2/45) and 2.2% (1/45), respectively. Observations demonstrated that D. canis slowly moved from a light area to a dark area. Skin samples were examined for cellular apoptosis by activated caspase3 immunohistochemical staining. Cells that surrounded the infected hair follicles were activated caspase3-positive, revealing cell apoptosis in infected follicles via the activation of caspase3. PMID:21867442

  18. The dog mite, Demodex canis: prevalence, fungal co-infection, reactions to light, and hair follicle apoptosis.

    PubMed

    Tsai, Yu-Jen; Chung, Wen-Cheng; Wang, Lian-Chen; Ju, Yu-Ten; Hong, Chin-Lin; Tsai, Yu-Yang; Li, Yi-Hung; Wu, Ying-Ling

    2011-01-01

    Infection rate, reaction to light, and hair follicle apoptosis are examined in the dogmite, Demodex canis Leydig (Prostigmata: Demodicidae), in dogs from the northern area of Taiwan. An analysis of relevant samples revealed 7.2% (73/1013) prevalence of D. canis infection. Infection during the investigation peaked each winter, with an average prevalence of 12.5% (32/255). The infection rates significantly varied in accordance with month, sex, age, and breed (p < 0.05). Most of the lesions were discovered on the backs of the infected animals, where the infection rate was 52.1% (38/73) (P < 0.05). The epidemiologic analysis of infection based on landscape area factor, found that employing a map-overlapping method showed a higher infection rate in the eastern distribution of Taiwan's northern area than other areas. Isolation tests for Microsporum canis Bodin (Onygenales: Arthrodermataceae) and Trichophyton mentagrophyte Robin (Blanchard) on the D. canis infected dogs revealed prevalence rates of 4.4% (2/45) and 2.2% (1/45), respectively. Observations demonstrated that D. canis slowly moved from a light area to a dark area. Skin samples were examined for cellular apoptosis by activated caspase3 immunohistochemical staining. Cells that surrounded the infected hair follicles were activated caspase3-positive, revealing cell apoptosis in infected follicles via the activation of caspase3.

  19. No causal association identified for human papillomavirus infections in lung cancer.

    PubMed

    Anantharaman, Devasena; Gheit, Tarik; Waterboer, Tim; Halec, Gordana; Carreira, Christine; Abedi-Ardekani, Behnoush; McKay-Chopin, Sandrine; Zaridze, David; Mukeria, Anush; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Mates, Dana; Janout, Vladimir; Foretova, Lenka; Bencko, Vladimir; Rudnai, Peter; Fabianova, Eleonora; Tjønneland, Anne; Travis, Ruth C; Boeing, Heiner; Quirós, J Ramón; Johansson, Mikael; Krogh, Vittorio; Bueno-de-Mesquita, H Bas; Kotanidou, Anastasia; Clavel-Chapelon, Françoise; Weiderpass, Elisabete; Johansson, Mattias; Pawlita, Michael; Scelo, Ghislaine; Tommasino, Massimo; Brennan, Paul

    2014-07-01

    Human papillomavirus (HPV) infections have been implicated in lung carcinogenesis, but causal associations remain uncertain. We evaluated a potential causal role for HPV infections in lung cancer through an analysis involving serology, tumor DNA, RNA, and p16 protein expression. Association between type-specific HPV antibodies and risk of lung cancer was examined among 3,083 cases and 4,328 controls in two case-control studies (retrospective) and one nested case-control study (prospective design). Three hundred and thirty-four available tumors were subjected to pathologic evaluation and subsequent HPV genotyping following stringent conditions to detect all high-risk and two low-risk HPV types. All HPV DNA-positive tumors were further tested for the expression of p16 protein and type-specific HPV mRNA. On the basis of the consistency of the results, although HPV11 and HPV31 E6 antibodies were associated with lung cancer risk in the retrospective study, no association was observed in the prospective design. Presence of type-specific antibodies correlated poorly with the presence of the corresponding HPV DNA in the tumor. Although nearly 10% of the lung tumors were positive for any HPV DNA (7% for HPV16 DNA), none expressed the viral oncogenes. No association was observed between HPV antibodies or DNA and lung cancer survival. In conclusion, we found no supportive evidence for the hypothesized causal association between HPV infections and lung cancer.

  20. Dust mite (image)

    MedlinePlus

    ... is a magnified photograph of a dust mite. Mites are carriers (vectors) of many important diseases including typhus (scrub and murine) and rickettsialpox. (Image courtesy of the Centers for Disease Control and ...

  1. Loss of social behaviours in populations of Pseudomonas aeruginosa infecting lungs of patients with cystic fibrosis.

    PubMed

    Jiricny, Natalie; Molin, Søren; Foster, Kevin; Diggle, Stephen P; Scanlan, Pauline D; Ghoul, Melanie; Johansen, Helle Krogh; Santorelli, Lorenzo A; Popat, Roman; West, Stuart A; Griffin, Ashleigh S

    2014-01-01

    Pseudomonas aeruginosa, is an opportunistic, bacterial pathogen causing persistent and frequently fatal infections of the lung in patients with cystic fibrosis. Isolates from chronic infections differ from laboratory and environmental strains in a range of traits and this is widely interpreted as the result of adaptation to the lung environment. Typically, chronic strains carry mutations in global regulation factors that could effect reduced expression of social traits, raising the possibility that competitive dynamics between cooperative and selfish, cheating strains could also drive changes in P. aeruginosa infections. We compared the expression of cooperative traits - biofilm formation, secretion of exo-products and quorum sensing (QS) - in P. aeruginosa isolates that were estimated to have spent different lengths of time in the lung based on clinical information. All three exo-products involved in nutrient acquisition were produced in significantly smaller quantities with increased duration of infection, and patterns across four QS signal molecules were consistent with accumulation over time of mutations in lasR, which are known to disrupt the ability of cells to respond to QS signal. Pyocyanin production, and the proportion of cells in biofilm relative to motile, free-living cells in liquid culture, did not change. Overall, our results confirm that the loss of social behaviour is a consistent trend with time spent in the lung and suggest that social dynamics are potentially relevant to understanding the behaviour of P. aeruginosa in lung infections. PMID:24454693

  2. Loss of social behaviours in populations of Pseudomonas aeruginosa infecting lungs of patients with cystic fibrosis.

    PubMed

    Jiricny, Natalie; Molin, Søren; Foster, Kevin; Diggle, Stephen P; Scanlan, Pauline D; Ghoul, Melanie; Johansen, Helle Krogh; Santorelli, Lorenzo A; Popat, Roman; West, Stuart A; Griffin, Ashleigh S

    2014-01-01

    Pseudomonas aeruginosa, is an opportunistic, bacterial pathogen causing persistent and frequently fatal infections of the lung in patients with cystic fibrosis. Isolates from chronic infections differ from laboratory and environmental strains in a range of traits and this is widely interpreted as the result of adaptation to the lung environment. Typically, chronic strains carry mutations in global regulation factors that could effect reduced expression of social traits, raising the possibility that competitive dynamics between cooperative and selfish, cheating strains could also drive changes in P. aeruginosa infections. We compared the expression of cooperative traits - biofilm formation, secretion of exo-products and quorum sensing (QS) - in P. aeruginosa isolates that were estimated to have spent different lengths of time in the lung based on clinical information. All three exo-products involved in nutrient acquisition were produced in significantly smaller quantities with increased duration of infection, and patterns across four QS signal molecules were consistent with accumulation over time of mutations in lasR, which are known to disrupt the ability of cells to respond to QS signal. Pyocyanin production, and the proportion of cells in biofilm relative to motile, free-living cells in liquid culture, did not change. Overall, our results confirm that the loss of social behaviour is a consistent trend with time spent in the lung and suggest that social dynamics are potentially relevant to understanding the behaviour of P. aeruginosa in lung infections.

  3. Mites and allergy.

    PubMed

    Fernández-Caldas, Enrique; Puerta, Leonardo; Caraballo, Luis

    2014-01-01

    Allergic diseases triggered by mite allergens include allergic rhinoconjunctivitis, asthma, atopic dermatitis and other skin diseases. Since the early discovery of the allergenic role of mites of the genus Dermatophagoides in the mid 1960s, numerous species have been described as the source of allergens capable of sensitizing and inducing allergic symptoms in sensitized and genetically predisposed individuals. The main sources of allergens in house dust worldwide are the fecal pellets of the mite species D. pteronyssinus, D. farinae, Euroglyphus maynei and the storage mites Blomia tropicalis, Lepidoglyphus destructor and Tyropahgus putrescentiae. Group 1 and 2 allergens are major house dust mite allergens. The main allergens in storage mites include fatty acid-binding proteins, tropomyosin and paramyosin homologues, apolipophorin-like proteins, α-tubulins and others, such as group 2, 5 and 7 allergens. Cross-reactivity is an important and common immunological feature among mites. Currently, purified native or recombinant allergens, epitope mapping, proteomic approaches and T cell proliferation techniques are being used to assess cross-reactivity. Mites contain potent enzymes capable of degrading a wide range of substrates. Most mite allergens are enzymes. Advances in genomics and molecular biology will improve our ability to understand the genetics of specific IgE responses to mites. Mite allergen avoidance and immunotherapy are the only two allergen-specific ways to treat mite-induced respiratory and cutaneous diseases.

  4. In Vitro Analysis of Metabolites Secreted during Infection of Lung Epithelial Cells by Cryptococcus neoformans.

    PubMed

    Liew, Kah Leong; Jee, Jap Meng; Yap, Ivan; Yong, Phelim Voon Chen

    2016-01-01

    Cryptococcus neoformans is an encapsulated basidiomycetous yeast commonly associated with pigeon droppings and soil. The opportunistic pathogen infects humans through the respiratory system and the metabolic implications of C. neoformans infection have yet to be explored. Studying the metabolic profile associated with the infection could lead to the identification of important metabolites associated with pulmonary infection. Therefore, the aim of the study was to simulate cryptococcal infection at the primary site of infection, the lungs, and to identify the metabolic profile and important metabolites associated with the infection at low and high multiplicity of infections (MOI). The culture supernatant of lung epithelial cells infected with C. neoformans at MOI of 10 and 100 over a period of 18 hours were analysed using gas chromatography mass spectrometry. The metabolic profiles obtained were further analysed using multivariate analysis and the pathway analysis tool, MetaboAnalyst 2.0. Based on the results from the multivariate analyses, ten metabolites were selected as the discriminatory metabolites that were important in both the infection conditions. The pathways affected during early C. neoformans infection of lung epithelial cells were mainly the central carbon metabolism and biosynthesis of amino acids. Infection at a higher MOI led to a perturbance in the β-alanine metabolism and an increase in the secretion of pantothenic acid into the growth media. Pantothenic acid production during yeast infection has not been documented and the β-alanine metabolism as well as the pantothenate and CoA biosynthesis pathways may represent underlying metabolic pathways associated with disease progression. Our study suggested that β-alanine metabolism and the pantothenate and CoA biosynthesis pathways might be the important pathways associated with cryptococcal infection. PMID:27054608

  5. In Vitro Analysis of Metabolites Secreted during Infection of Lung Epithelial Cells by Cryptococcus neoformans

    PubMed Central

    2016-01-01

    Cryptococcus neoformans is an encapsulated basidiomycetous yeast commonly associated with pigeon droppings and soil. The opportunistic pathogen infects humans through the respiratory system and the metabolic implications of C. neoformans infection have yet to be explored. Studying the metabolic profile associated with the infection could lead to the identification of important metabolites associated with pulmonary infection. Therefore, the aim of the study was to simulate cryptococcal infection at the primary site of infection, the lungs, and to identify the metabolic profile and important metabolites associated with the infection at low and high multiplicity of infections (MOI). The culture supernatant of lung epithelial cells infected with C. neoformans at MOI of 10 and 100 over a period of 18 hours were analysed using gas chromatography mass spectrometry. The metabolic profiles obtained were further analysed using multivariate analysis and the pathway analysis tool, MetaboAnalyst 2.0. Based on the results from the multivariate analyses, ten metabolites were selected as the discriminatory metabolites that were important in both the infection conditions. The pathways affected during early C. neoformans infection of lung epithelial cells were mainly the central carbon metabolism and biosynthesis of amino acids. Infection at a higher MOI led to a perturbance in the β-alanine metabolism and an increase in the secretion of pantothenic acid into the growth media. Pantothenic acid production during yeast infection has not been documented and the β-alanine metabolism as well as the pantothenate and CoA biosynthesis pathways may represent underlying metabolic pathways associated with disease progression. Our study suggested that β-alanine metabolism and the pantothenate and CoA biosynthesis pathways might be the important pathways associated with cryptococcal infection. PMID:27054608

  6. Cytokine and Chemokine Responses of Lung Exposed to Surrogate Viral and Bacterial Infections

    PubMed Central

    Liberati, Teresa A; Trammell, Rita A; Randle, Michelle; Barrett, Sarah; Toth, Linda A

    2013-01-01

    The use of in vitro models of complex in vivo systems has yielded many insights into the molecular mechanisms that underlie normal and pathologic physiology. However although the reduced complexity of these models is advantageous with regard to some research questions, the simplification may obscure or eliminate key influences that occur in vivo. We sought to examine this possibility with regard to the lung's response to infection, which may be inherent to resident lung cells or related to the systemic response to pulmonary infection. We used the inbred mouse strains C57BL/6J, DBA/2J, and B6.129S2-IL6tm1Kopf, which differ in their response to inflammatory and infectious challenges, to assess in vivo responses of lung to surrogate viral and bacterial infection and compared these with responses of cultured lung slices and human A549 cells. Pulmonary cytokine concentrations were measured both after in vivo inoculation of mice and in vitro exposure of lung slices and A549 cells to surrogate viral and bacterial infections. The data indicate similarities and differences in early lung responses to in vivo compared with in vitro exposure to these inflammatory substances. Therefore, resident cells in the lung appear to respond to some challenges in a strain-independent manner, whereas some stimuli may elicit recruitment of peripheral inflammatory cells that generate the subsequent response in a genotype-related manner. These results add to the body of information pointing to host genotype as a crucial factor in mediating the severity of microbial infections and demonstrate that some of these effects may not be apparent in vitro. PMID:23582418

  7. Human papillomavirus infection in lung vs. oral squamous cell carcinomas: a polymerase chain reaction study.

    PubMed

    Halimi, M; Morshedi Asl, S

    2011-06-01

    The role of Human Papillomavirus (HPV) has been suspected in pathogenesis of various malignancies; however, the available data are not conclusive. This study aimed to determine and compare the frequency of HPV infection in oral and lung Squamous Cell Carcinoma (SCC) by a sensitive method. Sixty specimens of oral and lung SCC (30 cases each one) were reevaluated in Tabriz Imam Reza Centre in a 24 month period. Following genomic DNA extract, the Polymerase Chain Reaction (PCR) amplification was performed in presence of specific MY11 and MY09 primers for HPV infection. Three cervical specimens and a combination of PCR solution lacking DNA plus healthy persons' DNA samples were employed as positive and negative controls, respectively. The oral group was significantly older than the lung group (68.90 vs. 56.67 y, p < 0.001) with more males in the latter (83.3 vs. 60%; p = 0.04). Percentages of HPV infection in the oral and lung groups were comparable (20 vs. 10%, respectively; p = 0.47). Majority of patients with HPV infection were older than 60 years (88.9%) or male (88.9%). In the oral group, all these cases were well differentiated and the majority was of lower lip origin (83.3%). In the lung group, 66.7% of these specimens were moderately differentiated and the origin was bronchus in all cases. In conclusion, the rate of HPV infection in lung and oral SCC samples is rather lower than the previous reports in the literature. This rate is apparently higher in the oral than the lung SCC specimens. PMID:22235505

  8. Cytokine expression in lungs of calves spontaneously infected with Mycoplasma bovis.

    PubMed

    Rodríguez, Francisco; González, Jorge F; Arbelo, Manuel; Zucca, Daniele; Fernández, Antonio

    2015-03-01

    Cytokine expression in the lung can play an important role during Mycoplasma bovis infection through leukocyte recruitment and activation, and the induction of a broad array of inflammatory mediators. To gain further insight into the pathogenesis of M. bovis-associated pneumonia, cytokine expression was examined, by immunohistochemical methods in formalin-fixed, paraffin wax-embedded tissues, in the lung of 20 calves spontaneously infected. Immunolabelling for tumor necrosis factor alpha (TNF)-α, interleukin-4 (IL-4), IL-10 and interferon-gamma (IFN-γ), was usually associated with pneumonia, particularly in macrophages and lymphocytes, and with the presence of M. bovis antigen. The expression was minimal in lungs from negative controls. The results demonstrated consistent upregulation of TNF-α, IL-4, IL-10 and IFN-γ expression during M. bovis-associated pneumonic lesions. These cytokines can participate in the immune and inflammatory responses during the pulmonary defense mechanisms against M. bovis infection. PMID:25331253

  9. Immunofluorescent characterization of lymphocytes in lungs of rats infected with Mycoplasma pulmonis.

    PubMed Central

    Davis, J K; Maddox, P A; Thorp, R B; Cassell, G H

    1980-01-01

    Immunofluorescence was used to determine the relative percentages of T and B lymphocytes found in the lungs of normal and Mycoplasma pulmonis-infected F344 rats. Lymphocytes recovered from controls were approximately 25% T, 25% B, and 50% unclassified mononuclear cells. Infected animals had a 2.6-fold greater number of T cells and IgA-bearing cells, and a 1.6-fold greater number of unclassified mononuclear cells. These studies show that M. pulmonis infection significantly alters lung lymphocyte populations both quantitatively and in subpopulation distribution. Therefore, future studies of rat lung lymphocytes should utilize animals known to be free of this ubiquitous respiratory pathogen. Images Fig. 1 PMID:7358429

  10. Animals devoid of pulmonary system as infection models in the study of lung bacterial pathogens

    PubMed Central

    López Hernández, Yamilé; Yero, Daniel; Pinos-Rodríguez, Juan M.; Gibert, Isidre

    2015-01-01

    Biological disease models can be difficult and costly to develop and use on a routine basis. Particularly, in vivo lung infection models performed to study lung pathologies use to be laborious, demand a great time and commonly are associated with ethical issues. When infections in experimental animals are used, they need to be refined, defined, and validated for their intended purpose. Therefore, alternative and easy to handle models of experimental infections are still needed to test the virulence of bacterial lung pathogens. Because non-mammalian models have less ethical and cost constraints as a subjects for experimentation, in some cases would be appropriated to include these models as valuable tools to explore host–pathogen interactions. Numerous scientific data have been argued to the more extensive use of several kinds of alternative models, such as, the vertebrate zebrafish (Danio rerio), and non-vertebrate insects and nematodes (e.g., Caenorhabditis elegans) in the study of diverse infectious agents that affect humans. Here, we review the use of these vertebrate and non-vertebrate models in the study of bacterial agents, which are considered the principal causes of lung injury. Curiously none of these animals have a respiratory system as in air-breathing vertebrates, where respiration takes place in lungs. Despite this fact, with the present review we sought to provide elements in favor of the use of these alternative animal models of infection to reveal the molecular signatures of host–pathogen interactions. PMID:25699030

  11. Genomic and functional analysis of the host response to acute simian varicella infection in the lung

    PubMed Central

    Arnold, Nicole; Girke, Thomas; Sureshchandra, Suhas; Nguyen, Christina; Rais, Maham; Messaoudi, Ilhem

    2016-01-01

    Varicella Zoster Virus (VZV) is the causative agent of varicella and herpes zoster. Although it is well established that VZV is transmitted via the respiratory route, the host-pathogen interactions during acute VZV infection in the lungs remain poorly understood due to limited access to clinical samples. To address these gaps in our knowledge, we leveraged a nonhuman primate model of VZV infection where rhesus macaques are intrabronchially challenged with the closely related Simian Varicella Virus (SVV). Acute infection is characterized by immune infiltration of the lung airways, a significant up-regulation of genes involved in antiviral-immunity, and a down-regulation of genes involved in lung development. This is followed by a decrease in viral loads and increased expression of genes associated with cell cycle and tissue repair. These data provide the first characterization of the host response required to control varicella virus replication in the lung and provide insight into mechanisms by which VZV infection can cause lung injury in an immune competent host. PMID:27677639

  12. Some Pathological Features of Lungs from Domestic and Wild Ruminants with Single and Mixed Protostrongylid Infections

    PubMed Central

    Panayotova-Pencheva, Mariana Stancheva; Alexandrov, Marin Tsvyatkov

    2010-01-01

    Lungs of 40 ruminants from Bulgaria with natural small lungworm (Nematoda: Protostrongylidae) infections were investigated, including 16 goats, 15 sheep, 7 mouflons, and 2 chamois. Muellerius capillaris, M. tenuispiculatus, Cystocaulus ocreatus, Neostrongylus linearis, and Protostrongylus brevispiculum infections were predominantly associated with nodular lesions, and Protostrongylus rufescens, Protostrongylus hobmaieri and Protostrongylus rupicaprae were associated with extensive lesions located mainly along the length of the large bronchi. The extent of lung abnormalities was most severe in the sheep. Alveolitis, parasite granulomas, damage of the alveolar septa, hyperplasia of the lung associated lymphoid tissue, and sclerosis of the parenchyma were found upon microscope examinations. In the goats compared to the sheep and mouflons, the terminal bronchi, bronchioles, and alveoli were more affected than the interstitium. Our research shows that the pathological lesions in the lungs of ruminants infected with protostrongylids depend on both the helminth and the host species. To our knowledge, this work is the first to provide data on the pathomorphological lesions in mouflon lungs infected with protostrongylids. PMID:20445790

  13. Phenotypes selected during chronic lung infection in cystic fibrosis patients: implications for the treatment of Pseudomonas aeruginosa biofilm infections.

    PubMed

    Ciofu, Oana; Mandsberg, Lotte F; Wang, Hengzhuang; Høiby, Niels

    2012-07-01

    During chronic lung infection of patients with cystic fibrosis, Pseudomonas aeruginosa can survive for long periods of time under the challenging selective pressure imposed by the immune system and antibiotic treatment as a result of its biofilm mode of growth and adaptive evolution mediated by genetic variation. Mucoidy, hypermutability and acquirement of mutational antibiotic resistance are important adaptive phenotypes that are selected during chronic P. aeruginosa infection. This review dicsusses the role played by these phenotypes for the tolerance of biofilms to antibiotics and show that mucoidy and hypermutability change the architecture of in vitro formed biofilms and lead to increase tolerance to antibiotics. Production of high levels of beta-lactamase impairs penetration of beta-lactam antibiotics due to inactivation of the antibiotic. In conclusion, these data underline the importance of biofilm prevention strategies by early aggressive antibiotic prophylaxis or therapy before phenotypic diversification during chronic lung infection of patients with cystic fibrosis.

  14. Macrophage-epithelial paracrine crosstalk inhibits lung edema clearance during influenza infection

    PubMed Central

    Peteranderl, Christin; Morales-Nebreda, Luisa; Lecuona, Emilia; Vadász, István; Morty, Rory E.; Schmoldt, Carole; Bespalowa, Julia; Pleschka, Stephan; Mayer, Konstantin; Gattenloehner, Stefan; Fink, Ludger; Lohmeyer, Juergen; Seeger, Werner; Sznajder, Jacob I.; Mutlu, Gökhan M.; Budinger, G.R. Scott

    2016-01-01

    Influenza A viruses (IAV) can cause lung injury and acute respiratory distress syndrome (ARDS), which is characterized by accumulation of excessive fluid (edema) in the alveolar airspaces and leads to hypoxemia and death if not corrected. Clearance of excess edema fluid is driven mostly by the alveolar epithelial Na,K-ATPase and is crucial for survival of patients with ARDS. We therefore investigated whether IAV infection alters Na,K-ATPase expression and function in alveolar epithelial cells (AECs) and the ability of the lung to clear edema. IAV infection reduced Na,K-ATPase in the plasma membrane of human and murine AECs and in distal lung epithelium of infected mice. Moreover, induced Na,K-ATPase improved alveolar fluid clearance (AFC) in IAV-infected mice. We identified a paracrine cell communication network between infected and noninfected AECs and alveolar macrophages that leads to decreased alveolar epithelial Na,K-ATPase function and plasma membrane abundance and inhibition of AFC. We determined that the IAV-induced reduction of Na,K-ATPase is mediated by a host signaling pathway that involves epithelial type I IFN and an IFN-dependent elevation of macrophage TNF-related apoptosis–inducing ligand (TRAIL). Our data reveal that interruption of this cellular crosstalk improves edema resolution, which is of biologic and clinical importance to patients with IAV-induced lung injury. PMID:26999599

  15. Suppression in lung defense responses after bacterial infection in rats pretreated with different welding fumes

    SciTech Connect

    Antonini, James M. . E-mail: jga6@cdc.gov; Taylor, Michael D.; Millecchia, Lyndell; Bebout, Alicia R.; Roberts, Jenny R.

    2004-11-01

    Epidemiology suggests that inhalation of welding fumes increases the susceptibility to lung infection. The effects of chemically distinct welding fumes on lung defense responses after bacterial infection were compared. Fume was collected during gas metal arc (GMA) or flux-covered manual metal arc (MMA) welding using two consumable electrodes: stainless steel (SS) or mild steel (MS). The fumes were separated into water-soluble and -insoluble fractions. The GMA-SS and GMA-MS fumes were found to be relatively insoluble, whereas the MMA-SS was highly water soluble, with the soluble fraction comprised of 87% Cr and 11% Mn. On day 0, male Sprague-Dawley rats were intratracheally instilled with saline (vehicle control) or the different welding fumes (0.1 or 2 mg/rat). At day 3, the rats were intratracheally inoculated with 5 x 10{sup 3} Listeria monocytogenes. On days 6, 8, and 10, left lungs were removed, homogenized, cultured overnight, and colony-forming units were counted to assess pulmonary bacterial clearance. Bronchoalveolar lavage (BAL) was performed on right lungs to recover phagocytes and BAL fluid to measure the production of nitric oxide (NO) and immunomodulatory cytokines, including tumor necrosis factor-{alpha} (TNF-{alpha}), interleukin (IL)-2, IL-6, and IL-10. In contrast to the GMA-SS, GMA-MS, and saline groups, pretreatment with the highly water soluble MMA-SS fume caused significant body weight loss, extensive lung damage, and a dramatic reduction in pulmonary clearance of L. monocytogenes after infection. NO concentrations in BAL fluid and lung immunostaining of inducible NO synthase were dramatically increased in rats pretreated with MMA-SS before and after infection. MMA-SS treatment caused a significant decrease in IL-2 and significant increases in TNF-{alpha}, IL-6, and IL-10 after infection. In conclusion, pretreatment with MMA-SS increased production of NO and proinflammatory cytokines (TNF-{alpha} and IL-6) after infection, which are likely

  16. Suppression in lung defense responses after bacterial infection in rats pretreated with different welding fumes.

    PubMed

    Antonini, James M; Taylor, Michael D; Millecchia, Lyndell; Bebout, Alicia R; Roberts, Jenny R

    2004-11-01

    Epidemiology suggests that inhalation of welding fumes increases the susceptibility to lung infection. The effects of chemically distinct welding fumes on lung defense responses after bacterial infection were compared. Fume was collected during gas metal arc (GMA) or flux-covered manual metal arc (MMA) welding using two consumable electrodes: stainless steel (SS) or mild steel (MS). The fumes were separated into water-soluble and -insoluble fractions. The GMA-SS and GMA-MS fumes were found to be relatively insoluble, whereas the MMA-SS was highly water soluble, with the soluble fraction comprised of 87% Cr and 11% Mn. On day 0, male Sprague-Dawley rats were intratracheally instilled with saline (vehicle control) or the different welding fumes (0.1 or 2 mg/rat). At day 3, the rats were intratracheally inoculated with 5 x 10(3) Listeria monocytogenes. On days 6, 8, and 10, left lungs were removed, homogenized, cultured overnight, and colony-forming units were counted to assess pulmonary bacterial clearance. Bronchoalveolar lavage (BAL) was performed on right lungs to recover phagocytes and BAL fluid to measure the production of nitric oxide (NO) and immunomodulatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-2, IL-6, and IL-10. In contrast to the GMA-SS, GMA-MS, and saline groups, pretreatment with the highly water soluble MMA-SS fume caused significant body weight loss, extensive lung damage, and a dramatic reduction in pulmonary clearance of L. monocytogenes after infection. NO concentrations in BAL fluid and lung immunostaining of inducible NO synthase were dramatically increased in rats pretreated with MMA-SS before and after infection. MMA-SS treatment caused a significant decrease in IL-2 and significant increases in TNF-alpha, IL-6, and IL-10 after infection. In conclusion, pretreatment with MMA-SS increased production of NO and proinflammatory cytokines (TNF-alpha and IL-6) after infection, which are likely responsible for

  17. Effects of Chinese medicinal herbs on a rat model of chronic Pseudomonas aeruginosa lung infection.

    PubMed

    Song, Z; Johansen, H K; Moser, C; Høiby, N

    1996-05-01

    The aim of the study was to evaluate the effects of two kinds of Chinese medicinal herbs, Isatis tinctoria L (ITL) and Daphne giraldii Nitsche (DGN), on a rat model of chronic Pseudomonas aeruginosa lung infection mimicking cystic fibrosis (CF). Compared to the control group, both drugs were able to reduce the incidence of lung abscess (p < 0.05) and to decrease the severity of the macroscopic pathology in lungs (p < 0.05). In the great majority of the rats, the herbs altered the inflammatory response in the lungs from an acute type inflammation, dominated by polymorphonuclear leukocytes (PMN), to a chronic type inflammation, dominated by mononuclear leukocytes (MN). DGN also improved the clearance of P. aeruginosa from the lungs (p < 0.03) compared with the control group. There were no significant differences between the control group and the two herbal groups with regard to serum IgG and IgA anti-P. aeruginosa sonicate antibodies. However, the IgM concentration in the ITL group was significantly lower than in the control group (p < 0.03). These results suggest that the two medicinal herbs might be helpful to CF patients with chronic P. aeruginosa lung infection, DGN being the most favorable. PMID:8703440

  18. Choriodecidual Infection Downregulates Angiogenesis and Morphogenesis Pathways in Fetal Lungs from Macaca Nemestrina

    PubMed Central

    McAdams, Ryan M.; Vanderhoeven, Jeroen; Beyer, Richard P.; Bammler, Theo K.; Farin, Federico M.; Liggitt, H. Denny; Kapur, Raj P.; Gravett, Michael G.; Rubens, Craig E.; Adams Waldorf, Kristina M.

    2012-01-01

    Background Intrauterine exposure to amniotic fluid (AF) cytokines is thought to predispose to bronchopulmonary dysplasia (BPD). We evaluated the effects of GBS exposure on RNA expression in fetal lung tissue to determine early molecular pathways associated with fetal lung injury that may progress to BPD. Methods Ten chronically catheterized pregnant monkeys (Macaca nemestrina) at 118–125 days gestation (term = 172 days) received choriodecidual inoculation of either: 1) Group B Streptococcus (n = 5) or 2) saline (n = 5). Cesarean section and fetal necropsy was performed in the first week after GBS or saline inoculation regardless of labor. RNA was extracted from fetal lungs and profiled by microarray. Results were analyzed using single gene, Gene Set, and Ingenuity Pathway Analysis. Validation was by RT-PCR and immunohistochemistry. Results Despite uterine quiescence in most cases, fetal lung injury occurred in four GBS cases (intra-alveolar neutrophils, interstitial thickening) and one control (peri-mortem hemorrhage). Significant elevations of AF cytokines (TNF-α, IL-8, IL-1β, IL-6) were detected in GBS versus controls (p<0.05). Lung injury was not directly caused by GBS, because GBS was undetectable by culture and PCR in the AF and fetal lungs. A total of 335 genes were differentially expressed greater than 1.5 fold (p<0.05) with GBS exposure associated with a striking upregulation of genes in innate and adaptive immunity and downregulation of pathways for angiogenesis, morphogenesis, and cellular growth and development. Conclusions A transient choriodecidual infection may induce fetal lung injury with profound alterations in the genetic program of the fetal lung before signs of preterm labor. Our results provide a window for the first time into early molecular pathways disrupting fetal lung angiogenesis and morphogenesis before preterm labor occurs, which may set the stage for BPD. A strategy to prevent BPD should target the fetus in utero to

  19. Deformed wing virus: replication and viral load in mites (Varroa destructor).

    PubMed

    Gisder, Sebastian; Aumeier, Pia; Genersch, Elke

    2009-02-01

    Deformed wing virus (DWV) normally causes covert infections but can have devastating effects on bees by inducing morphological deformity or even death when transmitted by the ectoparasitic mite Varroa destructor. In order to determine the role of V. destructor in the development of crippled wings, we analysed individual mites for the presence and replication of DWV. The results supported the correlation between viral replication in mites and morphologically deformed bees. Quantification of viral genome equivalents revealed that mites capable of inducing an overt DWV infection contained 10(10)-10(12) genome equivalents per mite. In contrast, mites which could not induce crippled wings contained a maximum of only 10(8) viral genome equivalents per mite. We conclude that the development of crippled wings not only depends on DWV transmission by V. destructor but also on viral replication in V. destructor and on the DWV titre in the parasitizing mites.

  20. Pseudomonas aeruginosa Evolutionary Adaptation and Diversification in Cystic Fibrosis Chronic Lung Infections

    PubMed Central

    Winstanley, Craig; O’Brien, Siobhan; Brockhurst, Michael A.

    2016-01-01

    Pseudomonas aeruginosa populations undergo a characteristic evolutionary adaptation during chronic infection of the cystic fibrosis (CF) lung, including reduced production of virulence factors, transition to a biofilm-associated lifestyle, and evolution of high-level antibiotic resistance. Populations of P. aeruginosa in chronic CF lung infections typically exhibit high phenotypic diversity, including for clinically important traits such as antibiotic resistance and toxin production, and this diversity is dynamic over time, making accurate diagnosis and treatment challenging. Population genomics studies reveal extensive genetic diversity within patients, including for transmissible strains the coexistence of highly divergent lineages acquired by patient-to-patient transmission. The inherent spatial structure and spatial heterogeneity of selection in the CF lung appears to play a key role in driving P. aeruginosa diversification. PMID:26946977

  1. Development of Liposomal Ciprofloxacin to Treat Lung Infections.

    PubMed

    Cipolla, David; Blanchard, Jim; Gonda, Igor

    2016-01-01

    Except for management of Pseudomonas aeruginosa (PA) in cystic fibrosis, there are no approved inhaled antibiotic treatments for any other diseases or for infections from other pathogenic microorganisms such as tuberculosis, non-tuberculous mycobacteria, fungal infections or potential inhaled biowarfare agents including Francisella tularensis, Yersinia pestis and Coxiella burnetii (which cause pneumonic tularemia, plague and Q fever, respectively). Delivery of an antibiotic formulation via the inhalation route has the potential to provide high concentrations at the site of infection with reduced systemic exposure to limit side effects. A liposomal formulation may improve tolerability, increase compliance by reducing the dosing frequency, and enhance penetration of biofilms and treatment of intracellular infections. Two liposomal ciprofloxacin formulations (Lipoquin(®) and Pulmaquin(®)) that are in development by Aradigm Corporation are described here. PMID:26938551

  2. Development of Liposomal Ciprofloxacin to Treat Lung Infections

    PubMed Central

    Cipolla, David; Blanchard, Jim; Gonda, Igor

    2016-01-01

    Except for management of Pseudomonas aeruginosa (PA) in cystic fibrosis, there are no approved inhaled antibiotic treatments for any other diseases or for infections from other pathogenic microorganisms such as tuberculosis, non-tuberculous mycobacteria, fungal infections or potential inhaled biowarfare agents including Francisella tularensis, Yersinia pestis and Coxiella burnetii (which cause pneumonic tularemia, plague and Q fever, respectively). Delivery of an antibiotic formulation via the inhalation route has the potential to provide high concentrations at the site of infection with reduced systemic exposure to limit side effects. A liposomal formulation may improve tolerability, increase compliance by reducing the dosing frequency, and enhance penetration of biofilms and treatment of intracellular infections. Two liposomal ciprofloxacin formulations (Lipoquin® and Pulmaquin®) that are in development by Aradigm Corporation are described here. PMID:26938551

  3. Disseminated Scedosporium/Pseudallescheria Infection after Double-Lung Transplantation in Patients with Cystic Fibrosis▿

    PubMed Central

    Morio, Florent; Horeau-Langlard, Delphine; Gay-Andrieu, Françoise; Talarmin, Jean-Philippe; Haloun, Alain; Treilhaud, Michelle; Despins, Philippe; Jossic, Frédérique; Nourry, Laurence; Danner-Boucher, Isabelle; Pattier, Sabine; Bouchara, Jean-Philippe; Le Pape, Patrice; Miegeville, Michel

    2010-01-01

    We report a case of disseminated Scedosporium/Pseudallescheria infection due to Pseudallescheria boydii sensu stricto after lung transplantation in a patient with cystic fibrosis. Dissemination occurred under voriconazole. Despite surgery and combination therapy with voriconazole, caspofungin, and terbinafine, the patient died 8 months after transplantation. Previously reported cases are reviewed. PMID:20220160

  4. Cross Protective Mucosal Immunity Mediated by Memory Th17 Cells against Streptococcus pneumoniae Lung Infection

    PubMed Central

    Wang, Yan; Jiang, Bin; Guo, Yongli; Li, Wenchao; Tian, Ying; Sonnenberg, Gregory F; Weiser, Jeffery N.; Ni, Xin; Shen, Hao

    2016-01-01

    Pneumonia caused by Streptococcus pneumoniae (Sp) remains a leading cause of serious illness and death worldwide. Immunization with conjugated pneumococcal vaccine has lowered the colonization rate and consequently invasive diseases by inducing serotype-specific antibodies. However, many of current pneumonia cases result from infection by serotype strains not included in the vaccine. In this study, we asked if cross-protection against lung infection by heterologous strains can be induced and investigated the underlying immune mechanism. We found that immune mice recovered from a prior infection were protected against heterologous Sp strains in the pneumonia challenge model, as evident by accelerated bacterial clearance, reduced pathology and apoptosis of lung epithelial cells. Sp infection in the lung induced strong Th17 responses at the lung mucosal site. Transfer of CD4+ T cells from immune mice provided heterologous protection against pneumonia, and this protection was abrogated by IL-17A blockade. Transfer of memory CD4+ T cells from IL-17A knockout mice failed to provide protection. These results indicate that memory Th17 cells played a key role in providing protection against pneumonia in a serotype independent manner and suggest the feasibility of developing a broadly protective vaccine against bacterial pneumonia by targeting mucosal Th17 T cells. PMID:27118490

  5. Green herring syndrome: bacterial infection in patients with mucormycosis cavitary lung disease.

    PubMed

    Peixoto, Driele; Hammond, Sarah P; Issa, Nicolas C; Madan, Rachna; Gill, Ritu R; Milner, Danny A; Colson, Yolonda L; Koo, Sophia; Baden, Lindsey R; Marty, Francisco M

    2014-03-01

    Mucormycosis is a life-threatening fungal disease in patients with hematological malignancies. The diagnosis of pulmonary mucormycosis is particularly challenging. We describe 3 mucormycosis cases with an uncommon presentation in patients whose cavitary lung disease was attributed to well documented bacterial infection, although evolution and reassessment established mucormycosis as the underlying disease. PMID:25734087

  6. Effects of Marijuana on the Lung and Its Defenses against Infection and Cancer.

    ERIC Educational Resources Information Center

    Tashkin, Donald P.

    1999-01-01

    Examines the many effects of marijuana use on the lungs. States that patients with pre-existing immune deficits are particularly vulnerable to marijuana-related pulmonary infections. However, warns that habitual use of marijuana may lead to respiratory cancer must await epidemiological studies, which are now possible since 30 years have passed…

  7. Detection of Mycobacterium tuberculosis in latently infected lungs by immunohistochemistry and confocal microscopy

    PubMed Central

    Eugenin, Eliseo; Kaplan, Gilla

    2014-01-01

    Detection of latent Mycobacterium tuberculosis is a challenge in the diagnosis of asymptomatic, subclinical tuberculosis. We report the development of an immunofluorescence technique to visualize and enumerate M. tuberculosis in latently infected rabbit lungs where no acid-fast–stained organisms were seen and no cultivable bacilli were obtained by the agar-plating method. PMID:25161200

  8. Combined Legionella and Escherichia coli lung infection after a tsunami disaster.

    PubMed

    Ebisawa, Kei; Yamada, Norihiro; Okada, Shinji; Suzuki, Yasuko; Satoh, Asami; Kobayashi, Makoto; Morikawa, Naoto

    2011-01-01

    Pulmonary infection after a tsunami is often polymicrobial and tends to form chronic pyogenic lung disease, necrotizing pneumonia, and empyemas. We report a combined pulmonary infection of Legionella and multiple antibiotic-resistant Escherichia coli in a previously well 75-year-old woman following immersion in tsunami waters 1 km inland from the Pacific coastline following the Tohoku Region Pacific Coast Earthquake of 2011. She needed drainage several times and the long-term use of multiple antibiotics according to the type of bacteria found and antibiotic susceptibility. We should be mindful of infections caused by multiple pathogens in the environment in Japan as a consequence of a tsunami disaster.

  9. Interleukin-17 Pathophysiology and Therapeutic Intervention in Cystic Fibrosis Lung Infection and Inflammation.

    PubMed

    Hsu, Daniel; Taylor, Patricia; Fletcher, Dave; van Heeckeren, Rolf; Eastman, Jean; van Heeckeren, Anna; Davis, Pamela; Chmiel, James F; Pearlman, Eric; Bonfield, Tracey L

    2016-09-01

    Cystic fibrosis (CF) is characterized by an excessive neutrophilic inflammatory response within the airway as a result of defective cystic fibrosis transmembrane receptor (CFTR) expression and function. Interleukin-17A induces airway neutrophilia and mucin production associated with Pseudomonas aeruginosa colonization, which is associated with the pathophysiology of cystic fibrosis. The objectives of this study were to use the preclinical murine model of cystic fibrosis lung infection and inflammation to investigate the role of IL-17 in CF lung pathophysiology and explore therapeutic intervention with a focus on IL-17. Cftr-deficient mice (CF mice) and wild-type mice (WT mice) infected with P. aeruginosa had robust IL-17 production early in the infection associated with a persistent elevated inflammatory response. Intratracheal administration of IL-17 provoked a neutrophilic response in the airways of WT and CF animals which was similar to that observed with P. aeruginosa infection. The neutralization of IL-17 prior to infection significantly improved the outcomes in the CF mice, suggesting that IL-17 may be a therapeutic target. We demonstrate in this report that the pathophysiological contribution of IL-17 may be due to the induction of chemokines from the epithelium which is augmented by a deficiency of Cftr and ongoing inflammation. These studies demonstrate the in vivo contribution of IL-17 in cystic fibrosis lung disease and the therapeutic validity of attenuating IL-17 activity in cystic fibrosis. PMID:27271746

  10. Allexivirus transmitted by eriophyid mites in garlic plants.

    PubMed

    Kang, Sang Gu; Koo, Bong Jin; Lee, Eun Tag; Chang, Moo Ung

    2007-11-01

    Viruses in garlic plants (Allium sativum L.) have accumulated and evolved over generations, resulting in serious consequences for the garlic trade around the world. These viral epidemics are also known to be caused by aphids and eriophyid mites (Aceria tulipae) carrying Potyviruses, Carlaviruses, and Allexiviruses. However, little is known about viral epidemics in garlic plants caused by eriophyid mites. Therefore, this study investigated the infection of garlic plants with Allexiviruses by eriophyid mites. When healthy garlic plants were cocultured with eriophyid mites, the leaves of the garlic plants developed yellow mosaic strips and became distorted. In extracts from the eriophyid mites, Allexiviruses were observed using immunosorbent electron microscopy (ISEM). From an immunoblot analysis, coat proteins against an Allexivirus garlic-virus antiserum were clearly identified in purified extracts from collected viral-infected garlic plants, eriophyid mites, and garlic plants infected by eriophyid mites. A new strain of GarV-B was isolated and named GarV-B Korea isolate 1 (GarV-B1). The ORF1 and ORF2 in GarV-B1 contained a typical viral helicase, RNA-directed RNA polymerase (RdRp), and triple gene block protein (TGBp) for viral movement between cells. The newly identified GarV-B1 was phylogenetically grouped with GarV-C and GarV-X in the Allexivirus genus. All the results in this study demonstrated that eriophyid mites are a transmitter insect species for Allexiviruses. PMID:18092468

  11. Spatiotemporal quantification of cell dynamics in the lung following influenza virus infection

    NASA Astrophysics Data System (ADS)

    Yin, Lu; Xu, Shuoyu; Cheng, Jierong; Zheng, Dahai; Limmon, Gino V.; Leung, Nicola H. N.; Rajapakse, Jagath C.; Chow, Vincent T. K.; Chen, Jianzhu; Yu, Hanry

    2013-04-01

    Lung injury caused by influenza virus infection is widespread. Understanding lung damage and repair progression post infection requires quantitative spatiotemporal information on various cell types mapping into the tissue structure. Based on high content images acquired from an automatic slide scanner, we have developed algorithms to quantify cell infiltration in the lung, loss and recovery of Clara cells in the damaged bronchioles and alveolar type II cells (AT2s) in the damaged alveolar areas, and induction of pro-surfactant protein C (pro-SPC)-expressing bronchiolar epithelial cells (SBECs). These quantitative analyses reveal: prolonged immune cell infiltration into the lung that persisted long after the influenza virus was cleared and paralleled with Clara cell recovery; more rapid loss and recovery of Clara cells as compared to AT2s; and two stages of SBECs from Scgb1a1+ to Scgb1a1-. These results provide evidence supporting a new mechanism of alveolar repair where Clara cells give rise to AT2s through the SBEC intermediates and shed light on the understanding of the lung damage and repair process. The approach and algorithms in quantifying cell-level changes in the tissue context (cell-based tissue informatics) to gain mechanistic insights into the damage and repair process can be expanded and adapted in studying other disease models.

  12. Vaccine-generated lung tissue–resident memory T cells provide heterosubtypic protection to influenza infection

    PubMed Central

    Zens, Kyra D.; Chen, Jun Kui; Farber, Donna L.

    2016-01-01

    Tissue-resident memory T cells (TRM) are a recently defined, noncirculating subset with the potential for rapid in situ protective responses, although their generation and role in vaccine-mediated immune responses is unclear. Here, we assessed TRM generation and lung-localized protection following administration of currently licensed influenza vaccines, including injectable inactivated influenza virus (IIV, Fluzone) and i.n. administered live-attenuated influenza virus (LAIV, FluMist) vaccines. We found that, while IIV preferentially induced strain-specific neutralizing antibodies, LAIV generated lung-localized, virus-specific T cell responses. Moreover, LAIV but not IIV generated lung CD4+ TRM and virus-specific CD8+ TRM, similar in phenotype to those generated by influenza virus infection. Importantly, these vaccine-generated TRM mediated cross-strain protection, independent of circulating T cells and neutralizing antibodies, which persisted long-term after vaccination. Interestingly, intranasal administration of IIV or injection of LAIV failed to elicit T cell responses or provide protection against viral infection, demonstrating dual requirements for respiratory targeting and a live-attenuated strain to establish TRM. The ability of LAIV to generate lung TRM capable of providing long-term protection against nonvaccine viral strains, as demonstrated here, has important implications for protecting the population against emergent influenza pandemics by direct fortification of lung-specific immunity. PMID:27468427

  13. Genome Wide Host Gene Expression Analysis in Chicken Lungs Infected with Avian Influenza Viruses

    PubMed Central

    Gandhale, Pradeep N.; Kumar, Himanshu; Kulkarni, Diwakar D.

    2016-01-01

    The molecular pathogenesis of avian influenza infection varies greatly with individual bird species and virus strain. The molecular pathogenesis of the highly pathogenic avian influenza virus (HPAIV) or the low pathogenic avian influenza virus (LPAIV) infection in avian species remains poorly understood. Thus, global immune response of chickens infected with HPAI H5N1 (A/duck/India/02CA10/2011) and LPAI H9N2 (A/duck/India/249800/2010) viruses was studied using microarray to identify crucial host genetic components responsive to these infection. HPAI H5N1 virus induced excessive expression of type I IFNs (IFNA and IFNG), cytokines (IL1B, IL18, IL22, IL13, and IL12B), chemokines (CCL4, CCL19, CCL10, and CX3CL1) and IFN stimulated genes (OASL, MX1, RSAD2, IFITM5, IFIT5, GBP 1, and EIF2AK) in lung tissues. This dysregulation of host innate immune genes may be the critical determinant of the severity and the outcome of the influenza infection in chickens. In contrast, the expression levels of most of these genes was not induced in the lungs of LPAI H9N2 virus infected chickens. This study indicated the relationship between host immune genes and their roles in pathogenesis of HPAIV infection in chickens. PMID:27071061

  14. GENETIC BASIS OF MURINE ANTIBACTERIAL DEFENSE TO STREPTOCOCCAL LUNG INFECTION

    EPA Science Inventory

    To evaluate the effect of genetic background and toll-like receptor 2 on antibacterial defense to streptococcal infection, eight genetically diverse strains of mice (A/J, DBA/2J, CAST/Ei, FVB/NJ, BALB/cJ, C57BL/6J, 129/SvImJ, and C3H/HeJ) and tlr2-deficient mice (C57BL/6

  15. Respiratory Failure due to Possible Donor-Derived Sporothrix schenckii Infection in a Lung Transplant Recipient

    PubMed Central

    Bahr, Nathan C.; Janssen, Katherine; Billings, Joanne; Loor, Gabriel; Green, Jaime S.

    2015-01-01

    Background. De novo and donor-derived invasive fungal infections (IFIs) contribute to morbidity and mortality in solid organ transplant (SOT) recipients. Reporting of donor-derived IFIs (DDIFIs) to the Organ Procurement Transplant Network has been mandated since 2005. Prior to that time no systematic monitoring of DDIFIs occurred in the United States. Case Presentation. We report a case of primary graft dysfunction in a 49-year-old male lung transplant recipient with diffuse patchy bilateral infiltrates likely related to pulmonary Sporothrix schenckii infection. The organism was isolated from a bronchoalveolar lavage on the second day after transplantation. Clinical and radiographic responses occurred after initiation of amphotericin B lipid formulation. Conclusion. We believe that this was likely a donor-derived infection given the early timing of the Sporothrix isolation after transplant in a bilateral single lung transplant recipient. This is the first case report of sporotrichosis in a lung transplant recipient. Our patient responded well to amphotericin induction therapy followed by maintenance therapy with itraconazole. The implications of donor-derived fungal infections and Sporothrix in transplant recipients are reviewed. Early recognition and management of these fungi are essential in improving outcomes. PMID:26697244

  16. Respiratory Failure due to Possible Donor-Derived Sporothrix schenckii Infection in a Lung Transplant Recipient.

    PubMed

    Bahr, Nathan C; Janssen, Katherine; Billings, Joanne; Loor, Gabriel; Green, Jaime S

    2015-01-01

    Background. De novo and donor-derived invasive fungal infections (IFIs) contribute to morbidity and mortality in solid organ transplant (SOT) recipients. Reporting of donor-derived IFIs (DDIFIs) to the Organ Procurement Transplant Network has been mandated since 2005. Prior to that time no systematic monitoring of DDIFIs occurred in the United States. Case Presentation. We report a case of primary graft dysfunction in a 49-year-old male lung transplant recipient with diffuse patchy bilateral infiltrates likely related to pulmonary Sporothrix schenckii infection. The organism was isolated from a bronchoalveolar lavage on the second day after transplantation. Clinical and radiographic responses occurred after initiation of amphotericin B lipid formulation. Conclusion. We believe that this was likely a donor-derived infection given the early timing of the Sporothrix isolation after transplant in a bilateral single lung transplant recipient. This is the first case report of sporotrichosis in a lung transplant recipient. Our patient responded well to amphotericin induction therapy followed by maintenance therapy with itraconazole. The implications of donor-derived fungal infections and Sporothrix in transplant recipients are reviewed. Early recognition and management of these fungi are essential in improving outcomes.

  17. Effect of a plant polyphenol-rich extract on the lung protease activities of influenza-virus-infected mice.

    PubMed

    Serkedjieva, Julia; Toshkova, Reneta; Antonova-Nikolova, Stefka; Stefanova, Tsvetanka; Teodosieva, Ani; Ivanova, Iskra

    2007-01-01

    Influenza infection was induced in white mice by intranasal inoculation of the virus A/Aichi/2/68 (H3N2). The lung protease and the protease-inhibitory activities were followed for 9 days after infection. The intranasal application of a polyphenol-rich extract (PC) isolated from Geranium sanguineum L. induced a continuous rise in the anti-protease activity but did not cause substantial changes in the lung protease activity of healthy mice. Influenza virus infection triggered a slight reduction in protease activity in the lungs at 5 and 48 h post infection (p.i.) and a marked increase at 24 h and 6 day p.i.. Protease inhibition in the lungs was reduced at 24 and 48 h p.i. and an increase was observed at 5 h and 6 and 9 days p.i.. PC treatment brought both activities to normal levels. The restoration of the examined parameters was consistent with a prolongation of mean survival time and reduction of mortality rate, infectious virus titre and lung consolidation. PC reinstated superoxide production by alveolar macrophages and increased their number in virus-infected mice. The favourable effect on the protease and the protease-inhibitory activities in the lungs of influenza-virus-infected mice apparently contributes to the overall protective effect of PC in the murine experimental influenza A/Aichi infection. The antiviral effect of the individual constituents was evaluated. PMID:17542152

  18. Interstitial lung disease associated with Equine Infectious Anemia Virus infection in horses.

    PubMed

    Bolfa, Pompei; Nolf, Marie; Cadoré, Jean-Luc; Catoi, Cornel; Archer, Fabienne; Dolmazon, Christine; Mornex, Jean-François; Leroux, Caroline

    2013-12-01

    EIA (Equine Infectious Anemia) is a blood-borne disease primarily transmitted by haematophagous insects or needle punctures. Other routes of transmission have been poorly explored. We evaluated the potential of EIAV (Equine Infectious Anemia Virus) to induce pulmonary lesions in naturally infected equids. Lungs from 77 EIAV seropositive horses have been collected in Romania and France. Three types of lesions have been scored on paraffin-embedded lungs: lymphocyte infiltration, bronchiolar inflammation, and thickness of the alveolar septa. Expression of the p26 EIAV capsid (CA) protein has been evaluated by immunostaining. Compared to EIAV-negative horses, 52% of the EIAV-positive horses displayed a mild inflammation around the bronchioles, 22% had a moderate inflammation with inflammatory cells inside the wall and epithelial bronchiolar hyperplasia and 6.5% had a moderate to severe inflammation, with destruction of the bronchiolar epithelium and accumulation of smooth muscle cells within the pulmonary parenchyma. Changes in the thickness of the alveolar septa were also present. Expression of EIAV capsid has been evidenced in macrophages, endothelial as well as in alveolar and bronchiolar epithelial cells, as determined by their morphology and localization. To summarize, we found lesions of interstitial lung disease similar to that observed during other lentiviral infections such as FIV in cats, SRLV in sheep and goats or HIV in children. The presence of EIAV capsid in lung epithelial cells suggests that EIAV might be responsible for the broncho-interstitial damages observed.

  19. Mixed Fungal Lung Infection with Aspergillus Fumigatus and Candida Albicans in a Immunocomprimised Patient: Case Report

    PubMed Central

    Vipparti, Haritha

    2014-01-01

    The frequency of invasive, opportunistic mycoses has increased significantly over the past 2 decades. In the immune-compromised host, many fungi, including species of fungi typically considered non-pathogenic, have the potential to cause serious morbidity and mortality. Here we report a rare case of mixed fungal infection of the lung with Candida albicans and Aspergillus fumigatus in a patient on prolonged steroid therapy. PMID:24959447

  20. [Two cases of lung infection due to Mycobacterium chelonae subsp. abscessus].

    PubMed

    Kawashima, T; Kioi, S; Arakawa, M

    1994-03-01

    Two cases of lung infection due to Mycobacterium chelonae subsp. abscessus are reported. Case 1, a 50-year-old female, was a secondary infection-type, and case 2, a 53-year-old female, was a primary infection-type. The 16 cases reported, between the ages of 29 and 76 years, there were 6 males and 10 females. The roentgenographic examinations, revealed that the ratio of the primary and secondary infection-type was 3:1. Effective agents for this organism has not been yet confirmed. In the present study, we treated two patients with AMK and IPM/CS, and obtained negative conversion of the sputum culture as well as improvement of roentgenographic features. PMID:8176285

  1. Intrinsic and environmental mutagenesis drive diversification and persistence of Pseudomonas aeruginosa in chronic lung infections.

    PubMed

    Rodríguez-Rojas, Alexandro; Oliver, Antonio; Blázquez, Jesús

    2012-01-01

    Pseudomonas aeruginosa is a versatile opportunistic pathogen causing a wide variety of hospital-acquired acute infections in immunocompromised patients as well as chronic respiratory infections in patients suffering from cystic fibrosis or other chronic respiratory diseases. Several traits contribute to its ability to colonize and persist in the lungs of chronically infected patients, including development of high resistance to antimicrobials and hypermutability, biofilm growth, and alginate hyperproduction, or a customized pathogenicity, which may include the loss of classical virulence factors and metabolic changes. Here we argue that a combination of both intrinsic and environmental mutagenesis leads to a high number of mutant variants in the population. The conducive environment then triggers a positive feedback loop leading to adaptation and persistence of P. aeruginosa, rendering these chronic infections almost impossible to eradicate. PMID:22080096

  2. The role of mites in the transmission and maintenance of Hantaan virus (Hantavirus: Bunyaviridae).

    PubMed

    Yu, Xue-jie; Tesh, Robert B

    2014-12-01

    This review examines the evidence indicating a role for parasitic mites in the transmission and maintenance of Hantaan virus in nature. The available data, much of it from recent studies in China, indicate that both trombiculid and gamasid mites are naturally infected with Hantaan virus and that infected mites can transmit the virus by bite to laboratory mice and transovarially (vertically) through eggs to their offspring. Collectively, these findings challenge the current paradigm of hantavirus transmission, namely, that rodents serve as the reservoir of human pathogenic hantaviruses in nature and that humans are infected with these viruses by inhalation of aerosols of infectious rodent excreta. Further research is needed to confirm the mite-hantavirus association and to determine if parasitic mites are in fact the major source and principal vectors of human pathogenic hantaviruses, such as Hantaan. If the mite hypothesis is correct, then it will significantly alter current concepts about the epidemiology, prevention, and control of human hantavirus infection.

  3. [Toll-like receptors expression in the lungs of human metapneumovirus infected mice and the effects of polyI:C on viral infection].

    PubMed

    Dou, Ying; Zhao, Yao; Zhang, Zhi-Yong; Zhao, Xiao-Dong

    2010-01-01

    To investigate the expression changes of Toll-like receptors (TLR) in the lungs of human metapneumovirus infected BALB/c mice, and to explore the effects of PolyI:C on viral replication, HMPV-infected group, PolyI:C+hMPV group, PolyI:C+DMED group and DMEM control group were set up for this study. All mice were sacrificed on day 1, 3, 5, 7, 9 and 16 post inoculation. Lungs were used for viral titration, pulmonary histopathology and detection of TLRs mRNA expression by RT-PCR and real-time PCR. Results showed that the levels of viral replication in the lungs of PolyI:C+hMPV infected mice were significantly decreased and lung inflammation were also lessened compared with those of hMPV infected mice. RT-PCR detection showed that mRNA levels of most TLRs were up-regulated (P < 0.05) in the lungs of hMPV infected group compared with DMEM group. Real time PCR assay showed that TLR7-8 mRNA significantly increased in hMPV infected group in a time-dependent manner. The level of TLR3 mRNA was significantly up-regulated in PolyI:C+hMPV group at the 24 hour after intranasal inoculation. The results showed that hMPV infection up-regulated the expression of TLRs in lungs of BALB/c mice and TLR7/8 pathway might play an important role in the start of natural immune response. PolyI:C was capable of inhibiting viral replication in the lung of mice and reducing lung inflammation probably through the early activation of TLR3.

  4. Cysticercoids of Anoplocephala magna (Eucestoda: Anoplocephalidae) experimentally grown in oribatid mites (Acari: Oribatida).

    PubMed

    Schuster, Rolf K; Coetzee, Louise

    2012-11-23

    Anoplocephala magna eggs found in the rectal content of a naturally infected zebra from South Africa were fed to Scheloribates pallidulus under laboratory condition. Mites remained in contact with the eggs for one week and were late kept for 30 days in an incubator at 28°C. At the end of the experiment, 19 out of 136 mites contained typical anoplocephalidae cysticercoids in their body cavity in numbers between one and three. The average size of the metacestodes varied depending on intensity of infection. Cysticercoid infected mites were less likely to carry mite eggs.

  5. Accumulation of activated CD4+ lymphocytes in the lung of individuals infected with HIV accompanied by increased virus production in patients with secondary infections.

    PubMed Central

    Franchini, M; Walker, C; Henrard, D R; Suter-Gut, D; Braun, P; Villiger, B; Suter, M

    1995-01-01

    The lung is continuously exposed to infectious and non-infectious agents causing cell activation. Activated cells in the lung such as antigen-presenting cells which harbour HIV may favour this organ as a site for virus production. To test this hypothesis, cells from blood and bronchoalveolar lavage (BAL) of HIV-infected patients and healthy controls were obtained and the activation of the cells were analysed by measuring the expression of IL-2 receptor, HLA-DR and VLA-1. The HIV-infected individuals were subdivided into 'lung symptomatic' or 'lung asymptomatic' patients, depending on the presence or absence of secondary lung diseases besides HIV. All HIV-infected individuals demonstrated a decreased number of CD4+ lymphocytes in blood; however, normal numbers of these cells were found in BAL. The activation state of CD4+ and CD8+ T lymphocytes in blood and BAL was higher in lymphocytes from HIV-infected patients compared with controls. The activation state was highest in the lung symptomatic group. Lung symptomatic patients and lung asymptomatic patients with extrapulmonary infections had increased levels of free virus in plasma. Four out of four individuals without or with only low amounts of cell-free HIV in plasma belonged to the symptom-free subgroup. These results suggest that microorganisms other than HIV may promote viral replication via antigen-driven accumulation and activation of CD4+ cells in the lung or other organs, and thus may be responsible for the loss of helper T cells and the progression of the disease. PMID:7586671

  6. Sterilizing immunity to influenza virus infection requires local antigen-specific T cell response in the lungs.

    PubMed

    Dutta, Avijit; Huang, Ching-Tai; Lin, Chun-Yen; Chen, Tse-Ching; Lin, Yung-Chang; Chang, Chia-Shiang; He, Yueh-Chia

    2016-01-01

    Sterilizing immunity is a unique immune status, which prevents effective virus infection into the host. It is different from the immunity that allows infection but with subsequent successful eradication of the virus. Pre-infection induces sterilizing immunity to homologous influenza virus challenge in ferret. In our antigen-specific experimental system, mice pre-infected with PR8 influenza virus through nasal route are likewise resistant to reinfection of the same strain of virus. The virus is cleared before establishment of effective infection. Intramuscular influenza virus injection confers protection against re-infection with facilitated virus clearance but not sterilizing immunity. Pre-infection and intramuscular injection generates comparable innate immunity and antibody response, but only pre-infection induces virus receptor reduction and efficient antigen-specific T cell response in the lungs. Pre-infection with nH1N1 influenza virus induces virus receptor reduction but not PR8-specific T cell immune response in the lungs and cannot prevent infection of PR8 influenza virus. Pre-infection with PR8 virus induced PR8-specific T cell response in the lungs but cannot prevent infection of nH1N1 virus either. These results reveal that antigen-specific T cell immunity is required for sterilizing immunity. PMID:27596047

  7. Sterilizing immunity to influenza virus infection requires local antigen-specific T cell response in the lungs

    PubMed Central

    Dutta, Avijit; Huang, Ching-Tai; Lin, Chun-Yen; Chen, Tse-Ching; Lin, Yung-Chang; Chang, Chia-Shiang; He, Yueh-Chia

    2016-01-01

    Sterilizing immunity is a unique immune status, which prevents effective virus infection into the host. It is different from the immunity that allows infection but with subsequent successful eradication of the virus. Pre-infection induces sterilizing immunity to homologous influenza virus challenge in ferret. In our antigen-specific experimental system, mice pre-infected with PR8 influenza virus through nasal route are likewise resistant to reinfection of the same strain of virus. The virus is cleared before establishment of effective infection. Intramuscular influenza virus injection confers protection against re-infection with facilitated virus clearance but not sterilizing immunity. Pre-infection and intramuscular injection generates comparable innate immunity and antibody response, but only pre-infection induces virus receptor reduction and efficient antigen-specific T cell response in the lungs. Pre-infection with nH1N1 influenza virus induces virus receptor reduction but not PR8-specific T cell immune response in the lungs and cannot prevent infection of PR8 influenza virus. Pre-infection with PR8 virus induced PR8-specific T cell response in the lungs but cannot prevent infection of nH1N1 virus either. These results reveal that antigen-specific T cell immunity is required for sterilizing immunity. PMID:27596047

  8. Sterilizing immunity to influenza virus infection requires local antigen-specific T cell response in the lungs

    NASA Astrophysics Data System (ADS)

    Dutta, Avijit; Huang, Ching-Tai; Lin, Chun-Yen; Chen, Tse-Ching; Lin, Yung-Chang; Chang, Chia-Shiang; He, Yueh-Chia

    2016-09-01

    Sterilizing immunity is a unique immune status, which prevents effective virus infection into the host. It is different from the immunity that allows infection but with subsequent successful eradication of the virus. Pre-infection induces sterilizing immunity to homologous influenza virus challenge in ferret. In our antigen-specific experimental system, mice pre-infected with PR8 influenza virus through nasal route are likewise resistant to reinfection of the same strain of virus. The virus is cleared before establishment of effective infection. Intramuscular influenza virus injection confers protection against re-infection with facilitated virus clearance but not sterilizing immunity. Pre-infection and intramuscular injection generates comparable innate immunity and antibody response, but only pre-infection induces virus receptor reduction and efficient antigen-specific T cell response in the lungs. Pre-infection with nH1N1 influenza virus induces virus receptor reduction but not PR8-specific T cell immune response in the lungs and cannot prevent infection of PR8 influenza virus. Pre-infection with PR8 virus induced PR8-specific T cell response in the lungs but cannot prevent infection of nH1N1 virus either. These results reveal that antigen-specific T cell immunity is required for sterilizing immunity.

  9. Class specific inhibition of house dust mite proteinases which cleave cell adhesion, induce cell death and which increase the permeability of lung epithelium

    PubMed Central

    Winton, Helen L; Wan, Hong; Cannell, Mark B; Thompson, Philip J; Garrod, David R; Stewart, Geoffrey A; Robinson, Clive

    1998-01-01

    House dust mite (HDM) allergens with cysteine and serine proteinase activity are risk factors for allergic sensitization and asthma. A simple method to fractionate proteinase activity from HDM faecal pellets into cysteine and serine class activity is described. Both proteinase fractions increased the permeability of epithelial cell monolayers. The effects of the serine proteinase fraction were inhibited by 4-(2-aminoethyl)-benzenesulphonyl fluoride hydrochloride (AEBSF) and soybean trypsin inhibitor (SBTI). The effects of the cysteine proteinase fraction could be inhibited by E-64. No reciprocity of action was found. Treatment of epithelial monolayers with either proteinase fraction caused breakdown of tight junctions (TJs). AEBSF inhibited TJ breakdown caused by the serine proteinase fraction, whereas E-64 inhibited the cysteine proteinase fraction. Agarose gel electrophoresis revealed that the proteinases induced DNA cleavage which was inhibited by the matrix metalloproteinase inhibitor BB-250. Compound E-64 inhibited DNA fragmentation caused by the cysteine proteinase fraction, but was without effect on the serine proteinase fraction. Staining of proteinase-treated cells with annexin V (AV) and propidium iodide (PI) revealed a diversity of cellular responses. Some cells stained only with AV indicating early apoptosis, whilst others were dead and stained with both AV and PI. HDM proteinases exert profound effects on epithelial cells which will promote allergic sensitization; namely disruption of intercellular adhesion, increased paracellular permeability and initiation of cell death. Attenuation of these actions by proteinase inhibitors leads to the conclusion that compounds designed to be selective for the HDM enzymes may represent a novel therapy for asthma. PMID:9720772

  10. Neonatal pneumococcal colonisation caused by Influenza A infection alters lung function in adult mice

    PubMed Central

    FitzPatrick, Meaghan; Royce, Simon G.; Langenbach, Shenna; McQualter, Jonathan; Reading, Patrick C.; Wijburg, Odilia; Anderson, Gary P.; Stewart, Alastair; Bourke, Jane; Bozinovski, Steven

    2016-01-01

    There is emerging epidemiological data to suggest that upper respiratory tract bacterial colonisation in infancy may increase the risk of developing respiratory dysfunction later in life, and respiratory viruses are known to precipitate persistent colonisation. This study utilized a neonatal mouse model of Streptococcus pneumonia (SP) and influenza A virus (IAV) co-infection, where bronchoalveolar leukocyte infiltration had resolved by adulthood. Only co-infection resulted in persistent nasopharyngeal colonisation over 40 days and a significant increase in airway resistance in response to in vivo methacholine challenge. A significant increase in hysteresivity was also observed in IAV and co-infected mice, consistent with ventilatory heterogeneity and structural changes in the adult lung. Airway hyper-responsiveness was not associated with a detectable increase in goblet cell transdifferentiation, peribronchial smooth muscle bulk or collagen deposition in regions surrounding the airways. Increased reactivity was not observed in precision cut lung slices challenged with methacholine in vitro. Histologically, the airway epithelium appeared normal and expression of epithelial integrity markers (ZO-1, occludin-1 and E-cadherin) were not altered. In summary, neonatal co-infection led to persistent nasopharyngeal colonisation and increased airway responsiveness that was not associated with detectable smooth muscle or mucosal epithelial abnormalities, however increased hysteresivity may reflect ventilation heterogeneity. PMID:26940954

  11. Ciprofloxacin-Loaded Inorganic-Organic Composite Microparticles To Treat Bacterial Lung Infection.

    PubMed

    Tewes, Frederic; Brillault, Julien; Lamy, Barbara; O'Connell, Peter; Olivier, Jean-Christophe; Couet, William; Healy, Anne Marie

    2016-01-01

    Ciprofloxacin (CIP) is an antibiotic that has been clinically trialed for the treatment of lung infections by aerosolization. However, CIP is rapidly systemically absorbed after lung administration, increasing the risk for subtherapeutic pulmonary concentrations and resistant bacteria selection. In the presence of calcium, CIP forms complexes that reduce its oral absorption. Such complexation may slow down CIP absorption from the lung thereby maintaining high concentration in this tissue. Thus, we developed inhalable calcium-based inorganic-organic composite microparticles to sustain CIP within the lung. The aerodynamics and micromeritic properties of the microparticles were characterized. FTIR and XRD analysis suggest that the inorganic component of the particles comprised amorphous calcium carbonate and amorphous calcium formate, and that CIP and calcium interact in a 1:1 stoichiometry in the particles. CIP was completely released from the microparticles within 7 h, with profiles showing a slight dependence on pH (5 and 7.4) compared to the dissolution of pure CIP. Transport studies of CIP across Calu-3 cell monolayers, in the presence of various calcium concentrations, showed a decrease of up to 84% in CIP apparent permeability. The apparent minimum inhibitory concentration of CIP against Pseudomonas aeruginosa and Staphylococcus aureus was not changed in the presence of the same calcium concentration. These results indicate that the designed particles should provide sustained levels of CIP with therapeutic effect in the lung. With these microparticles, it should be possible to control CIP pharmacokinetics within the lung, based on controlled CIP release from the particles and reduced apparent permeability across the epithelial barrier due to the cation-CIP interaction. PMID:26641021

  12. Mites and Wee Beasties.

    ERIC Educational Resources Information Center

    Reed, George H., Jr.

    1978-01-01

    A review is made of public health aspects of some arthropods that might be seen on a college or university campus. The diseases and infestations caused by mites, lice, bed bugs, fleas, and ticks are discussed. (JMF)

  13. Scabies mite, photomicrograph (image)

    MedlinePlus

    This is a photomicrograph of the scabies mite. This animal burrows in the skin, depositing both eggs and feces. Scabies infestation causes intense itching (pruritus) which leads to scratching and damage ...

  14. Scabies mite, photomicrograph (image)

    MedlinePlus

    This is a photomicrograph of the scabies mite. They burrows into the skin, depositing both eggs and feces. A scabies infestation causes intense itching (pruritus) which leads to scratching and damage ...

  15. Immunization protected well nourished mice but not undernourished ones from lung injury in Methicillin-resistant Staphylococcus aureus (MRSA) infection

    PubMed Central

    2009-01-01

    Background Staphylococcus aureus methicillin-resistant (MRSA) has been frequently isolated from endotracheal and lung puncture aspirates in malnourished children with pneumonia. In this work we evaluated the susceptibility of undernourished BALB/c mice and its ability to mount a protective immunity against MRSA with emphasis on the lung involvement. Results BALB/c mice submitted to a 20% dietary restriction during 20 days presented a significant decrease in body weight, lymphocyte number and also atrophy in thymus and intestinal epithelium. Determination of bacterial load by the number of colony forming units (CFU) indicated a similar susceptibility whereas the findings of Gram stain clearly suggested a higher amount of bacteria in the lungs of normal mice than in the undernourished ones. Immunization reduced bacterial growth in the lungs of normal mice but not in the undernourished ones. Histopathological analysis showed that inflammation appeared in the lungs from normal mice only after infection and that immunization prevented this pulmonary inflammatory process. On the other hand, undernourished mice presented lung inflammation even before infection. In addition, the degree of this inflammatory process did not change with infection or previous immunization. Conclusion Our results indicated that lung injury during MRSA infection is prevented by previous immunization in well nourished but not in undernourished mice. PMID:19930660

  16. Effect of quercetin supplementation on lung antioxidants after experimental influenza virus infection.

    PubMed

    Kumar, Pankaj; Khanna, Madhu; Srivastava, Vikram; Tyagi, Yogesh Kumar; Raj, Hanumanthrao G; Ravi, K

    2005-06-01

    In the mice, instillation of influenza virus A/Udorn/317/72(H3N2) intranasally resulted in a significant decrease in the pulmonary concentrations of catalase, reduced glutathione, and superoxide dismutase. There was a decrease in vitamin E level also. These effects were observed on the 5th day after viral instillation. Oral supplementation with quercetin simultaneous with viral instillation produced significant increases in the pulmonary concentrations of catalase, reduced glutathione, and superoxide dismutase. However, quercetin did not reverse the fall in vitamin E level associated with the viral infection. It is concluded that during influenza virus infection, there is "oxidative stress." Because quercetin restored the concentrations of many antioxidants, it is proposed that it may be useful as a drug in protecting the lung from the deleterious effects of oxygen derived free radicals released during influenza virus infection.

  17. Beneficial Effects of CpG-Oligodeoxynucleotide Treatment on Trauma and Secondary Lung Infection.

    PubMed

    Wanke-Jellinek, Lorenz; Keegan, Joshua W; Dolan, James W; Guo, Fei; Chen, Jianfei; Lederer, James A

    2016-01-15

    Although Streptococcus pneumoniae is usually found as a commensal in healthy individuals, it can act as a pathogen in trauma patients, causing such complications as early-onset pneumonia and sepsis. We discovered that treating mice with an A-class CpG-oligodeoxynucleotide (ODN) at 2 h after traumatic injury significantly improved mouse survival following early-onset secondary lung infection with S. pneumoniae. This study used mass cytometry (cytometry by time-of-flight) and Luminex technologies to characterize the cellular immune response to secondary S. pneumoniae lung infection at 1 and 3 d postinfection. We found increased expression of CD14, CD64, and PD-L1 on F4-80(+) and F4-80(+)CD11c(+) macrophages, CD11c(+) dendritic cells, and CD14(+)CD172a(+) cells after burn-injury and infection, supporting previous reports of innate immune cell activation in sepsis. CpG-ODN treatment at 2 h after burn-injury reversed these effects; improved pathogen clearance; and led to an increased expression of CD25, CD27, MHCII, and IL-17 on or in TCRγδ cells at 1 d postinfection. At 3 d postinfection, CpG-ODN treatment increased the expression of PD-L1 on innate cell subsets. Furthermore, we analyzed cytokine levels in lung-washout samples of TCRγδ cell-depleted (TCRγδ(-)) mice to demonstrate that the effects of CpG-ODN on cytokine expression after burn-injury and S. pneumoniae infection rely on functional TCRγδ cells. In summary, we demonstrate that cytometry by time-of-flight provides an effective strategy to systematically identify specific cellular phenotypic responses to trauma and bacterial pneumonia and to discover changes in immune system phenotypes associated with beneficial immunotherapy. PMID:26673136

  18. Effect of Quercetin on lipid peroxidation and changes in lung morphology in experimental influenza virus infection.

    PubMed

    Kumar, Pankaj; Sharma, Sonal; Khanna, MadhU; Raj, Hanumantharao Guru

    2003-06-01

    Influenza virus infection, induced experimentally in mice, was associated with marked changes in lung morphology viz. epithelial damage with focal areas of reactive papillary hyperplasia, infiltration of leukocytes and development of oxidative stress, as evidenced by increased superoxide radical production and lipid peroxidation (LPO) products by alveolar macrophages. These effects were observed on the 5th day after virus instillation. The levels of superoxide and LPO were measured spectrophotometrically by the nitroblue tetrazolium (NBT) assay and thiobarbituric acid reactive species (TBARS) assay, respectively. The former increased by 1.5-2 fold and the latter was raised by 85% when compared with normal control. Supplementation of intranasal viral instillation with the anti-oxidant, Quercetin, given orally, resulted in a significant decrease in the levels of both superoxide radicals and LPO products. There was also a significant decrease in the number of infiltrating cells. A mild to moderate protective effect was observed in lung morphology. Thus, Quercetin may be useful as a drug in reducing the oxidative stress induced by influenza virus infection in the lung, and protect it from the toxic effects of the free radicals.

  19. A20 Deficiency in Lung Epithelial Cells Protects against Influenza A Virus Infection

    PubMed Central

    Vereecke, Lars; Mc Guire, Conor; Sze, Mozes; Schuijs, Martijn J.; Willart, Monique; Itati Ibañez, Lorena; Hammad, Hamida; Lambrecht, Bart N.; Beyaert, Rudi; Saelens, Xavier; van Loo, Geert

    2016-01-01

    A20 negatively regulates multiple inflammatory signalling pathways. We here addressed the role of A20 in club cells (also known as Clara cells) of the bronchial epithelium in their response to influenza A virus infection. Club cells provide a niche for influenza virus replication, but little is known about the functions of these cells in antiviral immunity. Using airway epithelial cell-specific A20 knockout (A20AEC-KO) mice, we show that A20 in club cells critically controls innate immune responses upon TNF or double stranded RNA stimulation. Surprisingly, A20AEC-KO mice are better protected against influenza A virus challenge than their wild type littermates. This phenotype is not due to decreased viral replication. Instead host innate and adaptive immune responses and lung damage are reduced in A20AEC-KO mice. These attenuated responses correlate with a dampened cytotoxic T cell (CTL) response at later stages during infection, indicating that A20AEC-KO mice are better equipped to tolerate Influenza A virus infection. Expression of the chemokine CCL2 (also named MCP-1) is particularly suppressed in the lungs of A20AEC-KO mice during later stages of infection. When A20AEC-KO mice were treated with recombinant CCL2 the protective effect was abrogated demonstrating the crucial contribution of this chemokine to the protection of A20AEC-KO mice to Influenza A virus infection. Taken together, we propose a mechanism of action by which A20 expression in club cells controls inflammation and antiviral CTL responses in response to influenza virus infection. PMID:26815999

  20. Comparison of four lung scoring systems for the assessment of the pathological outcomes derived from Actinobacillus pleuropneumoniae experimental infections

    PubMed Central

    2014-01-01

    Background In this study, four lung lesion scoring methods (Slaughterhouse Pleurisy Evaluation System [SPES], Consolidation Lung Lesion Score [LLS], Image analyses [IA] and Ratio of lung weight/body weight [LW/BW]) were compared for the assessment of the different pathological outcomes derived from an Actinobacillus pleuropneumoniae (App) experimental infection model. Moreover, pathological data was coupled with clinical (fever, inappetence and clinical score), production (average daily weigh gain [ADWG]) and diagnostic (PCR, ELISA and bacterial isolation) parameters within the four infection outcomes (peracute, acute, subclinically infected and non-infected). Results From the 61 inoculated animals, 9 were classified as peracute (presence of severe App-like clinical signs and lesions and sudden death or euthanasia shortly after inoculation), 31 as acutely affected (presence of App-like clinical signs and lesions and survival until the end of the experiment), 12 as subclinically infected (very mild or no clinical signs but App infection confirmed) and 9 as non-infected animals (lack of App-like clinical signs and lack of evidence of App infection). A significant correlation between all lung lesion scoring systems was found with the exception of SPES score versus LW/BW. SPES showed a statistically significant association with all clinical, production and diagnostic (with the exception of PCR detection of App in the tonsil) variables assessed. LLS and IA showed similar statistically significant associations as SPES, with the exception of seroconversion against App at necropsy. In contrast, LW/BW was statistically associated only with App isolation in lungs, presence of App-like lesions and ELISA OD values at necropsy. Conclusions In conclusion, SPES, LLS and IA are economic, fast and easy-to-perform lung scoring methods that, in combination with different clinical and diagnostic parameters, allow the characterization of different outcomes after App infection. PMID

  1. Unorthodox long-term aerosolized ampicillin use for methicillin-susceptible Staphylococcus aureus lung infection in a cystic fibrosis patient.

    PubMed

    Máiz, Luis; Lamas, Adelaida; Fernández-Olmos, Ana; Suárez, Lucrecia; Cantón, Rafael

    2009-05-01

    Staphylococcus aureus is a significant cause of pulmonary colonization in cystic fibrosis (CF) patients. The optimal strategy of therapy in chronically infected patients with this pathogen is not yet established. We report a successful long-term aerosolized ampicillin treatment of a 14-year-old girl with chronic symptomatic S. aureus lung infection.

  2. Neurotrophic and neuroimmune responses to early-life Pseudomonas aeruginosa infection in rat lungs.

    PubMed

    Cardenas, Silvia; Scuri, Mario; Samsell, Lennie; Ducatman, Barbara; Bejarano, Pablo; Auais, Alexander; Doud, Melissa; Mathee, Kalai; Piedimonte, Giovanni

    2010-09-01

    Early-life respiratory infection with Pseudomonas aeruginosa is common in children with cystic fibrosis or immune deficits. Although many of its clinical manifestations involve neural reflexes, little information is available on the peripheral nervous system of infected airways. This study sought to determine whether early-life infection triggers a neurogenic-mediated immunoinflammatory response, the mechanisms of this response, and its relationship with other immunoinflammatory pathways. Weanling and adult rats were inoculated with suspensions containing P. aeruginosa (PAO1) coated on alginate microspheres suspended in Tris-CaCl(2) buffer. Five days after infection, rats were injected with capsaicin to stimulate nociceptive nerves in the airway mucosa, and microvascular permeability was measured using Evans blue as a tracer. PAO1 increased neurogenic inflammation in the extra- and intrapulmonary compartments of weanlings but not in adults. The mechanism involves selective overexpression of NGF, which is critical for the local increase in microvascular permeability and for the infiltration of polymorphonuclear leukocytes into infected lung parenchyma. These effects are mediated in part by induction of downstream inflammatory cytokines and chemokines, especially IL-1beta, IL-18, and leptin. Our data suggest that neurogenic-mediated immunoinflammatory mechanisms play important roles in airway inflammation and hyperreactivity associated with P. aeruginosa when infection occurs early in life. PMID:20543002

  3. Antipseudomonal Bacteriophage Reduces Infective Burden and Inflammatory Response in Murine Lung

    PubMed Central

    Pabary, Rishi; Singh, Charanjit; Morales, Sandra; Bush, Andrew; Alshafi, Khalid; Bilton, Diana; Alton, Eric W. F. W.; Smithyman, Anthony

    2015-01-01

    As antibiotic resistance increases, there is a need for new therapies to treat infection, particularly in cystic fibrosis (CF), where Pseudomonas aeruginosa is a ubiquitous pathogen associated with increased morbidity and mortality. Bacteriophages are an attractive alternative treatment, as they are specific to the target bacteria and have no documented side effects. The efficacy of phage cocktails was established in vitro. Two P. aeruginosa strains were taken forward into an acute murine infection model with bacteriophage administered either prophylactically, simultaneously, or postinfection. The infective burden and inflammation in bronchoalveolar lavage fluid (BALF) were assessed at various times. With low infective doses, both control mice and those undergoing simultaneous phage treatment cleared P. aeruginosa infection at 48 h, but there were fewer neutrophils in BALF of phage-treated mice (median, 73.2 × 104/ml [range, 35.2 to 102.1 × 104/ml] versus 174 × 104/ml [112.1 to 266.8 × 104/ml], P < 0.01 for the clinical strain; median, 122.1 × 104/ml [105.4 to 187.4 × 104/ml] versus 206 × 104/ml [160.1 to 331.6 × 104/ml], P < 0.01 for PAO1). With higher infective doses of PAO1, all phage-treated mice cleared P. aeruginosa infection at 24 h, whereas infection persisted in all control mice (median, 1,305 CFU/ml [range, 190 to 4,700 CFU/ml], P < 0.01). Bacteriophage also reduced CFU/ml in BALF when administered postinfection (24 h) and both CFU/ml and inflammatory cells in BALF when administered prophylactically. A reduction in soluble inflammatory cytokine levels in BALF was also demonstrated under different conditions. Bacteriophages are efficacious in reducing both the bacterial load and inflammation in a murine model of P. aeruginosa lung infection. This study provides proof of concept for future clinical trials in patients with CF. PMID:26574007

  4. Risk of serious infection in patients with rheumatoid arthritis-associated interstitial lung disease.

    PubMed

    Zamora-Legoff, Jorge A; Krause, Megan L; Crowson, Cynthia S; Ryu, Jay H; Matteson, Eric L

    2016-10-01

    The objective of this study is to assess the occurrence of and risk factors for serious infections in rheumatoid arthritis (RA)-associated interstitial lung disease (ILD). All patients with RA-ILD (ACR 1987 criteria for RA) seen at a single center from 1998 to 2014 were identified and manually screened for study inclusion. Follow-up data were abstracted until death or December 31, 2015. Serious infection was defined as requiring antimicrobial therapy and hospitalization. Risk of infection was analyzed by person-year (py) methods using time-dependent covariates started when the medication was first used and stopped 30 days after the medication was discontinued. Of the 181 included patients, 87 (48 %) were female. The mean age at ILD diagnosis was 67.4 (±9.9) years, and median follow-up time was 3.1 (range: 0.01 to 14.8) years. Higher infection rates were observed during the first year after ILD diagnosis (14.1 per 100 py) than subsequently (5.7 per 100 py; p = 0.001). Pneumonia was the most common (3.9 per 100 py). Overall infection risk was higher in organizing pneumonia (OP) (27.1 per 100 py) than usual interstitial pneumonia (7.7 per 100 py) or non-specific interstitial pneumonia (5.5 per 100 py) (p < 0.001). The highest infection rate observed was with a daily prednisone use >10 mg per day (15.4 per 100 py). Patients with RA-ILD are at risk of serious infection. Prednisone use >10 mg per day was associated with higher rates of infection. Immunosuppressive drug use governed by concern for risk of infection in patients with ILD resulting in channeling bias cannot be excluded. PMID:27448151

  5. Exaggerated Acute Lung Injury and Impaired Antibacterial Defenses During Staphylococcus aureus Infection in Rats with the Metabolic Syndrome

    PubMed Central

    Feng, Xiaomei; Maze, Mervyn; Koch, Lauren G.; Britton, Steven L.; Hellman, Judith

    2015-01-01

    Rats with Metabolic Syndrome (MetaS) have a dysregulated immune response to the aseptic trauma of surgery. We hypothesized that rats with MetaS would have dysregulated inflammation, increased lung injury, and less effective antibacterial defenses during Staphylococcus (S.) aureus sepsis as compared to rats without MetaS. Low capacity runner (LCR; a model of MetaS) and high capacity runner (HCR) rats were challenged intravenously with S. aureus bacteria. After 48 h, inflammatory mediators and bacteria were quantified in the blood, bronchoalveolar lavage fluid (BALF), and lung homogenates. Lungs were analyzed histologically. BALF protein and lung wet-dry ratios were quantified to assess for vascular leak. Endpoints were compared in infected LCR vs HCR rats. LCR rats had higher blood and lung S. aureus counts, as well as higher levels of IL-6 in plasma, lungs and BALF, MIP-2 in plasma and lung, and IL-17A in lungs. Conversely, LCR rats had lower levels of IL-10 in plasma and lungs. Although lactate levels, and liver and renal function tests were similar between groups, LCR rats had higher BALF protein and lung wet-dry ratios, and more pronounced acute lung injury histologically. During S. aureus bacteremia, as compared with HCR rats, LCR (MetaS) rats have heightened pro-inflammatory responses, accompanied by increased acute lung injury and vascular leak. Notably, despite an augmented pro-inflammatory phenotype, LCR rats have higher bacterial levels in their blood and lungs. The MetaS state may exacerbate lung injury and vascular leak by attenuating the inflammation-resolving response, and by weakening antimicrobial defenses. PMID:25978669

  6. Exaggerated Acute Lung Injury and Impaired Antibacterial Defenses During Staphylococcus aureus Infection in Rats with the Metabolic Syndrome.

    PubMed

    Feng, Xiaomei; Maze, Mervyn; Koch, Lauren G; Britton, Steven L; Hellman, Judith

    2015-01-01

    Rats with Metabolic Syndrome (MetaS) have a dysregulated immune response to the aseptic trauma of surgery. We hypothesized that rats with MetaS would have dysregulated inflammation, increased lung injury, and less effective antibacterial defenses during Staphylococcus (S.) aureus sepsis as compared to rats without MetaS. Low capacity runner (LCR; a model of MetaS) and high capacity runner (HCR) rats were challenged intravenously with S. aureus bacteria. After 48 h, inflammatory mediators and bacteria were quantified in the blood, bronchoalveolar lavage fluid (BALF), and lung homogenates. Lungs were analyzed histologically. BALF protein and lung wet-dry ratios were quantified to assess for vascular leak. Endpoints were compared in infected LCR vs HCR rats. LCR rats had higher blood and lung S. aureus counts, as well as higher levels of IL-6 in plasma, lungs and BALF, MIP-2 in plasma and lung, and IL-17A in lungs. Conversely, LCR rats had lower levels of IL-10 in plasma and lungs. Although lactate levels, and liver and renal function tests were similar between groups, LCR rats had higher BALF protein and lung wet-dry ratios, and more pronounced acute lung injury histologically. During S. aureus bacteremia, as compared with HCR rats, LCR (MetaS) rats have heightened pro-inflammatory responses, accompanied by increased acute lung injury and vascular leak. Notably, despite an augmented pro-inflammatory phenotype, LCR rats have higher bacterial levels in their blood and lungs. The MetaS state may exacerbate lung injury and vascular leak by attenuating the inflammation-resolving response, and by weakening antimicrobial defenses.

  7. Tobramycin inhalation powder (TOBI Podhaler) for the treatment of lung infection in patients with cystic fibrosis.

    PubMed

    Vazquez-Espinosa, E; Marcos, C; Alonso, T; Giron, R M; Gomez-Punter, R M; Garcia-Castillo, E; Zamora, E; Cisneros, C; Garcia, J; Valenzuela, C; Ancochea, J

    2016-01-01

    Cystic fibrosis (CF) is an autosomal recessive inherited disease secondary to a defect in the CF transmembrane conductance regulator gene (CFTR). Mortality in CF is associated with impairment of lung function in which bacterial infection plays a fundamental role. The microorganism Pseudomonas aeruginosa (P. aeruginosa) is a marker of poor prognosis. Tobramycin was the first parenteral antibiotic to be used as inhaled medication in CF. Owing to its beneficial effects; it was subsequently used in designed inhaled formulations. The first formulation was the inhalation solution, which improved lung function, lowered hospitalization rates, and reduced the courses of intravenous antibiotic. However, the high associated costs and time necessary to administer the medication negatively affected quality of life. The recent development of tobramycin inhalation powder has optimized treatment. The dry powder inhaler is a simple device that reduces administration time and improves adherence. As there is no risk of bacterial contamination, disinfection is unnecessary.

  8. Increased lung epithelial permeability in HIV-infected patients with isolated cytotoxic T-lymphocytic alveolitis

    SciTech Connect

    Meignan, M.; Guillon, J.M.; Denis, M.; Joly, P.; Rosso, J.; Carette, M.F.; Baud, L.; Parquin, F.; Plata, F.; Debre, P. )

    1990-05-01

    HIV-related lymphocytic alveolitis is common in HIV-seropositive patients without lung infection or tumor. In some of them a fraction of alveolar lymphocytes are HIV-specific cytotoxic T-lymphocytes (CTL) bearing the CD8 and D44 cell surface markers and capable of killing HIV-infected alveolar macrophages. In order to evaluate the in vivo effect of these CTL on lung function, we measured the pulmonary clearance of aerosolized 99mTc-diethylene triamine penta-acetate (DTPA-CI) on 24 occasions in 22 patients with lymphocytic alveolitis. DTPA-CI has been selected as a highly sensitive test to detect injury of the lung epithelium. In 13 of the patients, we found a high DTPA-CI of 4.56 +/- 2.54%.min-1 (mean +/- SD), suggesting an increase of the epithelial permeability. The lymphocytic alveolitis was then characterized by a high cellularity, a high proportion of lymphocytes (59 +/- 18%), mainly composed of CD8+D44+ T-lymphocytes (149 +/- 109 cells/mm3), which spontaneously exhibited a cytolytic activity against the autologous alveolar macrophages in a standard 51Cr release assay. In the remaining 11 patients, DTPA-CI was normal (less than 1.78%.min-1), lymphocytic alveolitis being characterized by a low number or an absence of CD8+D44+ alveolar lymphocytes (9 +/- 13 cells/mm3) with no significant cytolytic activity. In the whole group, a significant correlation (r = 0.74, p = 0.0004) was found between the DTPA-CI and the number of CD8+D44+ lymphocytes and their cytotoxic activity against alveolar macrophages. Altogether, these results suggest that an injury of the lung epithelium could result from a HIV-specific CTL-induced immunologic conflict.

  9. Isolation and purification of Mycobacterium tuberculosis from H37Rv infected guinea pig lungs.

    PubMed

    Shi, Libin; Ryan, Gavin J; Bhamidi, Suresh; Troudt, JoLynn; Amin, Anita; Izzo, Angelo; Lenaerts, Anne J; McNeil, Michael R; Belisle, John T; Crick, Dean C; Chatterjee, Delphi

    2014-09-01

    Evidence suggests that Mycobacterium tuberculosis grown in vivo may have a different phenotypic structure from its in vitro counterpart. In order to study the differences between in vivo and in vitro grown bacilli, it is important to establish a reliable method for isolating and purifying M. tuberculosis from infected tissue. In this study, we developed an optimal method to isolate bacilli from the lungs of infected guinea pigs, which was also shown to be applicable to the interferon-γ gene knockout mouse model. Briefly, 1) the infected lungs were thoroughly homogenized; 2) a four step enzymatic digestion was utilized to reduce the bulk of the host tissue using collagenase, DNase I and pronase E; 3) residual contamination by the host tissue debris was successfully reduced using percoll density gradient centrifugation. These steps resulted in a protocol such that relatively clean, viable bacilli can be isolated from the digested host tissue homogenate in about 50% yield. These bacilli can further be used for analytical studies of the more stable cellular components such as lipid, peptidoglycan and mycolic acid.

  10. Ochroconis gallopavum infection in a lung transplant recipient: report of a case.

    PubMed

    Brokalaki, E I; Sommerwerck, U; von Heinegg, E H; Hillen, U

    2012-11-01

    Disseminated phaeohyphomycoses are rare infections caused by dematiaceous fungi. Ochroconis gallopavum is a neurotropic dematiaceous mold responsible for life-threatening respiratory and central nervous system infections in domestic poultry and in immunologically compromised humans. The world literature describes only 13 previous O gallopavum infections in solid organ transplant recipients. We report herein an O gallopavum phaeohyphomycosis with involvement of skin in a transplant recipient. A 69-year-old white man with a history of bilateral lung transplantation 6 years ago presented with acute onset of severe respiratory distress. Chest X-ray showed no evidence of pneumonia. Lung function showed bronchiolitis obliterans syndrome. Excision biopsy was performed because of a suspected pigmented basal cell carcinoma. Histopathology revealed dermal granulomatous dermatitis, focally suppurative, dominated by epitheloid cells with brownish round fungi. Further microbiological work-up of the biopsy specimen subsequently revealed O gallopavum as the causative organism. No brain involvement was observed. Antimycotic therapy with voriconazole 200 mg twice a day was immediately initiated and the patient was treated for 3 months. Additional intravenous therapy with tobramycin and imipenem was started upon detection of Enterobacter clocae and Enterococci in the sputum. The patient recovered during the next few weeks and was discharged on day 26. PMID:23146522

  11. Pharmacodynamics of Ceftazidime and Avibactam in Neutropenic Mice with Thigh or Lung Infection

    PubMed Central

    Melchers, Maria J.; van Mil, Anita C.; Lagarde, Claudia M.; Schuck, Virna J.; Nichols, Wright W.

    2015-01-01

    Avibactam is a new non-β-lactam β-lactamase inhibitor that shows promising restoration of ceftazidime activity against microorganisms producing Ambler class A extended-spectrum β-lactamases (ESBLs) and carbapenemases such as KPCs, class C β-lactamases (AmpC), and some class D enzymes. To determine optimal dosing combinations of ceftazidime-avibactam for treating infections with ceftazidime-resistant Pseudomonas aeruginosa, pharmacodynamic responses were explored in murine neutropenic thigh and lung infection models. Exposure-response relationships for ceftazidime monotherapy were determined first. Subsequently, the efficacy of adding avibactam every 2 h (q2h) or q8h to a fixed q2h dose of ceftazidime was determined in lung infection for two strains. Dosing avibactam q2h was significantly more efficacious, reducing the avibactam daily dose for static effect by factors of 2.7 and 10.1, whereas the mean percentage of the dosing interval that free drug concentrations remain above the threshold concentration of 1 mg/liter (%fT>CT 1 mg/liter) yielding bacteriostasis was similar for both regimens, with mean values of 21.6 (q2h) and 18.5 (q8h). Dose fractionation studies of avibactam in both the thigh and lung models indicated that the effect of avibactam correlated well with %fT>CT 1 mg/liter. This parameter of avibactam was further explored for four P. aeruginosa strains in the lung model and six in the thigh model. Parameter estimates of %fT>CT 1 mg/liter for avibactam ranged from 0 to 21.4% in the lung model and from 14.1 to 62.5% in the thigh model to achieve stasis. In conclusion, addition of avibactam enhanced the effect of ceftazidime, which was more pronounced at frequent dosing and well related with %fT>CT 1 mg/liter. The thigh model appeared more stringent, with higher values, ranging up to 62.5% fT>CT 1 mg/liter, required for a static effect. PMID:26525790

  12. Cytotoxic immune responses in the lungs correlate to disease severity in patients with hantavirus infection.

    PubMed

    Rasmuson, J; Pourazar, J; Mohamed, N; Lejon, K; Evander, M; Blomberg, A; Ahlm, C

    2016-04-01

    Hantavirus infections may cause severe and sometime life-threatening lung failure. The pathogenesis is not fully known and there is an urgent need for effective treatment. We aimed to investigate the association between pulmonary viral load and immune responses, and their relation to disease severity. Bronchoscopy with sampling of bronchoalveolar lavage (BAL) fluid was performed in 17 patients with acute Puumala hantavirus infection and 16 healthy volunteers acting as controls. Lymphocyte subsets, granzyme concentrations, and viral load were determined by flow cytometry, enzyme-linked immunosorbent assay (ELISA), and quantitative reverse transcription polymerase chain reaction (RT-PCR), respectively. Analyses of BAL fluid revealed significantly higher numbers of activated CD8(+) T cells and natural killer (NK) cells, as well as higher concentrations of the cytotoxins granzymes A and B in hantavirus-infected patients, compared to controls. In patients, Puumala hantavirus RNA was detected in 88 % of BAL cell samples and correlated inversely to the T cell response. The magnitude of the pulmonary cytotoxic lymphocyte response correlated to the severity of disease and systemic organ dysfunction, in terms of need for supplemental oxygen treatment, hypotension, and laboratory data indicating renal failure, cardiac dysfunction, vascular leakage, and cell damage. Regulatory T cell numbers were significantly lower in patients compared to controls, and may reflect inadequate immune regulation during hantavirus infection. Hantavirus infection elicits a pronounced cytotoxic lymphocyte response in the lungs. The magnitude of the immune response was associated with disease severity. These results give insights into the pathogenesis and possibilities for new treatments. PMID:26873376

  13. A Biomathematical Model of Pneumococcal Lung Infection and Antibiotic Treatment in Mice

    PubMed Central

    Schirm, Sibylle; Ahnert, Peter; Wienhold, Sandra; Mueller-Redetzky, Holger; Nouailles-Kursar, Geraldine; Loeffler, Markus; Witzenrath, Martin; Scholz, Markus

    2016-01-01

    Pneumonia is considered to be one of the leading causes of death worldwide. The outcome depends on both, proper antibiotic treatment and the effectivity of the immune response of the host. However, due to the complexity of the immunologic cascade initiated during infection, the latter cannot be predicted easily. We construct a biomathematical model of the murine immune response during infection with pneumococcus aiming at predicting the outcome of antibiotic treatment. The model consists of a number of non-linear ordinary differential equations describing dynamics of pneumococcal population, the inflammatory cytokine IL-6, neutrophils and macrophages fighting the infection and destruction of alveolar tissue due to pneumococcus. Equations were derived by translating known biological mechanisms and assuming certain response kinetics. Antibiotic therapy is modelled by a transient depletion of bacteria. Unknown model parameters were determined by fitting the predictions of the model to data sets derived from mice experiments of pneumococcal lung infection with and without antibiotic treatment. Time series of pneumococcal population, debris, neutrophils, activated epithelial cells, macrophages, monocytes and IL-6 serum concentrations were available for this purpose. The antibiotics Ampicillin and Moxifloxacin were considered. Parameter fittings resulted in a good agreement of model and data for all experimental scenarios. Identifiability of parameters is also estimated. The model can be used to predict the performance of alternative schedules of antibiotic treatment. We conclude that we established a biomathematical model of pneumococcal lung infection in mice allowing predictions regarding the outcome of different schedules of antibiotic treatment. We aim at translating the model to the human situation in the near future. PMID:27196107

  14. Genome-Wide Identification of Klebsiella pneumoniae Fitness Genes during Lung Infection

    PubMed Central

    Breen, Paul; Deornellas, Valerie; Mu, Qiao; Zhao, Lili; Wu, Weisheng; Cavalcoli, James D.; Mobley, Harry L. T.

    2015-01-01

    ABSTRACT Klebsiella pneumoniae is an urgent public health threat because of resistance to carbapenems, antibiotics of last resort against Gram-negative bacterial infections. Despite the fact that K. pneumoniae is a leading cause of pneumonia in hospitalized patients, the bacterial factors required to cause disease are poorly understood. Insertion site sequencing combines transposon mutagenesis with high-throughput sequencing to simultaneously screen thousands of insertion mutants for fitness defects during infection. Using the recently sequenced K. pneumoniae strain KPPR1 in a well-established mouse model of pneumonia, insertion site sequencing was performed on a pool of >25,000 transposon mutants. The relative fitness requirement of each gene was ranked based on the ratio of lung to inoculum read counts and concordance between insertions in the same gene. This analysis revealed over 300 mutants with at least a 2-fold fitness defect and 69 with defects ranging from 10- to >2,000-fold. Construction of 6 isogenic mutants for use in competitive infections with the wild type confirmed their requirement for lung fitness. Critical fitness genes included those for the synthesis of branched-chain and aromatic amino acids that are essential in mice and humans, the transcriptional elongation factor RfaH, and the copper efflux pump CopA. The majority of fitness genes were conserved among reference strains representative of diverse pathotypes. These results indicate that regulation of outer membrane components and synthesis of amino acids that are essential to its host are critical for K. pneumoniae fitness in the lung. PMID:26060277

  15. Alterations in cysteine proteinase content of rat lung associated with development of Pneumocystis carinii infection.

    PubMed Central

    Hayes, D J; Stubberfield, C R; McBride, J D; Wilson, D L

    1991-01-01

    The rate of hydrolysis of three cysteine-type proteinase substrates, N-benzyloxycarbonyl-Arg-Arg-4-methyl-7-coumarylamide (AMC) (cathepsin B), Arg-AMC (cathepsin H), and N-benzyloxycarbonyl-Phe-Arg-AMC (cathepsin L), were determined in rat lung throughout the time course of the induction of Pneumocystis carinii infection by immunosuppression. Cathepsin B-like and cathepsin L-like activities fell below control values initially, but from week 8 of the immunosuppressive treatment significant increases above the control were noted. Cathepsin H-like activity was greater than control levels from week 3, and by week 12 it was 7,600% of the mean control value. When compared with the relative degree of infection, as assessed from the number of cysts present in lung impression smears, cathepsin B-like and cathepsin L-like activities were significantly increased only at heavy parasite burdens while cathepsin H-like activity displayed a close correlation with parasite number (r = 0.884; P less than 0.001). Activity was detected in lysates of purified P. carinii with all three substrates. Treatment of heavily infected animals with co-trimoxazole cleared the lungs of P. carinii, and this was accompanied by a marked reduction in proteinase activity, in particular, cathepsin H-like activity, which fell from 108- to 3-fold the mean control value following drug treatment. Analysis of cathepsin H isozyme patterns by fluorography following isoelectric focusing revealed differences between treated and control lung samples. In the immunosuppressed group, there was a time-dependent increase in the intensity of some of the bands observed in the controls and an appearance of several novel bands which corresponded to bands observed in lysates of P. carinii. It is likely, therefore, that the increased proteinase activity observed in the treated group is due, at least in part, to isozymes from P. carinii; consequently, cathepsin H-like activity might be of use diagnostically in the

  16. Mite infestations of man contracted from dogs and cats.

    PubMed

    Thomsett, L R

    1968-07-13

    Acarine infestations of the dog and cat are transmissible to man. The relation between age incidence in the host, duration of disease, and circumstances under which the animal is kept are stated. Fifty out of 65 human contacts at risk to 42 infected dogs and cats showed lesions of mite infestation; 48% of these lesions were confined to the arms and torso.It is important to consider animal mite infestation in the differential diagnosis of human pruritic and papular skin disease.

  17. Pseudomonas aeruginosa Uses Multiple Pathways To Acquire Iron during Chronic Infection in Cystic Fibrosis Lungs

    PubMed Central

    Konings, Anna F.; Martin, Lois W.; Sharples, Katrina J.; Roddam, Louise F.; Latham, Roger; Reid, David W.

    2013-01-01

    Pseudomonas aeruginosa chronically infects the lungs of more than 80% of adult patients with cystic fibrosis (CF) and is a major contributor to the progression of disease pathology. P. aeruginosa requires iron for growth and has multiple iron uptake systems that have been studied in bacteria grown in laboratory culture. The purpose of this research was to determine which of these are active during infection in CF. RNA was extracted from 149 sputum samples obtained from 23 CF patients. Reverse transcription–quantitative real-time PCR (RT-qPCR) was used to measure the expression of P. aeruginosa genes encoding transport systems for the siderophores pyoverdine and pyochelin, for heme, and for ferrous ions. Expression of P. aeruginosa genes could be quantified in 89% of the sputum samples. Expression of genes associated with siderophore-mediated iron uptake was detected in most samples but was at low levels in some samples, indicating that other iron uptake mechanisms are active. Expression of genes encoding heme transport systems was also detected in most samples, indicating that heme uptake occurs during infection in CF. feoB expression was detected in all sputum samples, implying an important role for ferrous ion uptake by P. aeruginosa in CF. Our data show that multiple P. aeruginosa iron uptake mechanisms are active in chronic CF infection and that RT-qPCR of RNA extracted from sputum provides a powerful tool for investigating bacterial physiology during infection in CF. PMID:23690396

  18. Pseudomonas aeruginosa uses multiple pathways to acquire iron during chronic infection in cystic fibrosis lungs.

    PubMed

    Konings, Anna F; Martin, Lois W; Sharples, Katrina J; Roddam, Louise F; Latham, Roger; Reid, David W; Lamont, Iain L

    2013-08-01

    Pseudomonas aeruginosa chronically infects the lungs of more than 80% of adult patients with cystic fibrosis (CF) and is a major contributor to the progression of disease pathology. P. aeruginosa requires iron for growth and has multiple iron uptake systems that have been studied in bacteria grown in laboratory culture. The purpose of this research was to determine which of these are active during infection in CF. RNA was extracted from 149 sputum samples obtained from 23 CF patients. Reverse transcription-quantitative real-time PCR (RT-qPCR) was used to measure the expression of P. aeruginosa genes encoding transport systems for the siderophores pyoverdine and pyochelin, for heme, and for ferrous ions. Expression of P. aeruginosa genes could be quantified in 89% of the sputum samples. Expression of genes associated with siderophore-mediated iron uptake was detected in most samples but was at low levels in some samples, indicating that other iron uptake mechanisms are active. Expression of genes encoding heme transport systems was also detected in most samples, indicating that heme uptake occurs during infection in CF. feoB expression was detected in all sputum samples, implying an important role for ferrous ion uptake by P. aeruginosa in CF. Our data show that multiple P. aeruginosa iron uptake mechanisms are active in chronic CF infection and that RT-qPCR of RNA extracted from sputum provides a powerful tool for investigating bacterial physiology during infection in CF. PMID:23690396

  19. The role of onion-associated fungi in bulb mite infestation and damage to onion seedlings.

    PubMed

    Ofek, Tal; Gal, Shira; Inbar, Moshe; Lebiush-Mordechai, Sara; Tsror, Leah; Palevsky, Eric

    2014-04-01

    In Israel Rhizoglyphus robini is considered to be a pest in its own right, even though the mite is usually found in association with fungal pathogens. Plant protection recommendations are therefore to treat germinating onions seedlings, clearly a crucial phase in crop production, when mites are discovered. The aim of this study was to determine the role of fungi in bulb mite infestation and damage to germinating onion seedlings. Accordingly we (1) evaluated the effect of the mite on onion seedling germination and survival without fungi, (2) compared the attraction of the mite to species and isolates of various fungi, (3) assessed the effect of a relatively non-pathogenic isolate of Fusarium oxysporum on mite fecundity, and (4) determined the effects of the mite and of F. oxysporum separately and together, on onion seedling germination and sprout development. A significant reduction of seedling survival was recorded only in the 1,000 mites/pot treatment, after 4 weeks. Mites were attracted to 6 out of 7 collected fungi isolates. Mite fecundity on onion sprouts infested with F. oxysporum was higher than on non-infested sprouts. Survival of seedlings was affected by mites, fungi, and their combination. Sprouts on Petri dishes after 5 days were significantly longer in the control and mite treatments than both fungi treatments. During the 5-day experiment more mites were always found on the fungi-infected sprouts than on the non-infected sprouts. Future research using suppressive soils to suppress soil pathogens and subsequent mite damage is proposed.

  20. Choriodecidual Group B Streptococcal Infection Induces miR-155-5p in the Fetal Lung in Macaca nemestrina

    PubMed Central

    McAdams, Ryan M.; Bierle, Craig J.; Boldenow, Erica; Weed, Samantha; Tsai, Jesse; Beyer, Richard P.; MacDonald, James W.; Bammler, Theo K.; Liggitt, H. Denny; Farin, Federico M.; Vanderhoeven, Jeroen

    2015-01-01

    The mechanisms underlying fetal lung injury remain poorly defined. MicroRNAs (miRNAs) are small noncoding, endogenous RNAs that regulate gene expression and have been implicated in the pathogenesis of lung disease. Using a nonhuman primate model of choriodecidual infection, we sought to determine if differentially expressed miRNAs were associated with acute fetal lung injury. After inoculating 10 chronically catheterized pregnant monkeys (Macaca nemestrina) with either group B streptococcus (GBS) at 1 × 106 CFU (n = 5) or saline (n = 5) in the choriodecidual space, we extracted fetal lung mRNA and miRNA and profiled the changes in expression by microarray analysis. We identified 9 differentially expressed miRNAs in GBS-exposed fetal lungs, but of these, only miR-155-5p was validated by quantitative reverse transcription-PCR (P = 0.02). Significantly elevated miR-155-5p expression was also observed when immortalized human fetal airway epithelial (FeAE) cells were exposed to proinflammatory cytokines (interleukin-6 [IL-6] and tumor necrosis factor alpha [TNF-α]). Overexpression of miR-155-5p in FeAE cells in turn increased the production of IL-6 and CXCL10/gamma interferon-induced protein 10, which are implicated in leukocyte recruitment but also in protection from lung injury. Interestingly, while miR-155-5p decreased fibroblast growth factor 9 (FGF9) expression in a luciferase reporter assay, FGF9 levels were actually increased in GBS-exposed fetal lungs in vivo. FGF9 overexpression is associated with abnormal lung development. Thus, upregulation of miR-155-5p may serve as a compensatory mechanism to lessen the increase in FGF9 and prevent aberrant lung development. Understanding the complicated networks regulating lung development in the setting of infection is a key step in identifying how to prevent fetal lung injury leading to bronchopulmonary dysplasia. PMID:26195546

  1. [Diagnostic imaging and therapeutic implications in lung infections in patients with HIV-1 infection].

    PubMed

    Carella, E; Moschini, G L; Romanelli, F; Bossalini, G; Alberici, F; Viale, P; Ratti, G

    1997-05-01

    We studied retrospectively 132 episodes of infectious pneumonias in 89 patients examined from 1990 to 1995. Pneumocystis carinii was found to be the most common cause of pneumonia (33 patients). The other causes were: Streptococcus pneumoniae (15), Mycobacterium tuberculosis (14), Pseudomonas aeruginosa (8), Staphylococcus aureus (5), Cytomegalovirus (4), Haemophilus influentiae (4), Mycobacterium avium intracellulare (2), Klebsiella pneumoniae (2), E. coli (2), Serratia marcescens (1). No etiologic agent was found in 40 cases. We stress the need of a more frequent use of invasive diagnostic procedures in the study of focal lung consolidations because this radiologic sign is highly aspecific and may be caused by too many different pathogenic agents, needing different therapies-i.e., Streptococcus pneumoniae (15 cases), Pseudomonas aeruginosa (8), Staphylococcus aureus (5), Klebsiella pneumoniae (2), Escherichia coli (2), Pneumocystis carinii, Serratia marcescens and Haemophilus influentiae (1). Since there is an increase in mortality among patients treated with empiric antibiotic therapy, we stress the need of the routinary use of bronchoalveolar lavage in HIV+ patients with lung consolidation to perform specific therapy. Moreover, Pneumocystis carinii is by far the most frequent cause of diffuse interstitial infiltrates, and PCP has very suggestive clinical (dyspnea), radiologic (diffuse perihilar interstitial infiltrates; ground glass opacities; pneumatoceles) and laboratory (CD3+CD4 < 200/mcl; LDH > 600 UI/dl; PO2 < 70 mmHg) patterns, always related to the discovery of Pneumocystis carinii in escreatum. Thus, we decided to treat 15 patients with specific therapy for Pneumocystis carinii pneumonia with the above diagnostic algorithm, obtaining in all of them complete clinical and radiologic recovery. To conclude, in critical patients, invasive procedures should be performed only in the cases in which PCP is clinically improbable.

  2. Inhibition of autophagy ameliorates acute lung injury caused by avian influenza A H5N1 infection.

    PubMed

    Sun, Yang; Li, Chenggang; Shu, Yuelong; Ju, Xiangwu; Zou, Zhen; Wang, Hongliang; Rao, Shuan; Guo, Feng; Liu, Haolin; Nan, Wenlong; Zhao, Yan; Yan, Yiwu; Tang, Jun; Zhao, Chen; Yang, Peng; Liu, Kangtai; Wang, Shunxin; Lu, Huijun; Li, Xiao; Tan, Lei; Gao, Rongbao; Song, Jingdong; Gao, Xiang; Tian, Xinlun; Qin, Yingzhi; Xu, Kai-Feng; Li, Dangsheng; Jin, Ningyi; Jiang, Chengyu

    2012-02-21

    The threat of a new influenza pandemic has existed since 1997, when the highly pathogenic H5N1 strain of avian influenza A virus infected humans in Hong Kong and spread across Asia, where it continued to infect poultry and people. The human mortality rate of H5N1 infection is about 60%, whereas that of seasonal H1N1 infection is less than 0.1%. The high mortality rate associated with H5N1 infection is predominantly a result of respiratory failure caused by acute lung injury; however, how viral infection contributes to this disease pathology is unclear. Here, we used electron microscopy to show the accumulation of autophagosomes in H5N1-infected lungs from a human cadaver and mice, as well as in infected A549 human epithelial lung cells. We also showed that H5N1, but not seasonal H1N1, induced autophagic cell death in alveolar epithelial cells through a pathway involving the kinase Akt, the tumor suppressor protein TSC2, and the mammalian target of rapamycin. Additionally, we suggest that the hemagglutinin protein of H5N1 may be responsible for stimulating autophagy. When applied prophylactically, reagents that blocked virus-induced autophagic signaling substantially increased the survival rate of mice and substantially ameliorated the acute lung injury and mortality caused by H5N1 infection. We conclude that the autophagic cell death of alveolar epithelial cells likely plays a crucial role in the high mortality rate of H5N1 infection, and we suggest that autophagy-blocking agents might be useful as prophylactics and therapeutics against infection of humans by the H5N1 virus. PMID:22355189

  3. Interactions between natural enemies: Effect of a predatory mite on transmission of the fungus Neozygites floridana in two-spotted spider mite populations.

    PubMed

    Trandem, Nina; Berdinesen, Ronny; Pell, Judith K; Klingen, Ingeborg

    2016-02-01

    Introducing the predatory mite Phytoseiulus persimilis into two-spotted spider mite, Tetranychus urticae, populations significantly increased the proportion of T. urticae infected with the spider mite pathogen Neozygites floridana in one of two experiments. By the final sampling occasion, the number of T. urticae in the treatment with both the predator and the pathogen had declined to zero in both experiments, while in the fungus-only treatment T. urticae populations still persisted (20-40 T. urticae/subsample). Releasing P. persimilis into crops in which N. floridana is naturally present has the potential to improve spider mite control more than through predation alone.

  4. Diffuse interstitial and multiple cavitary lung lesions due to Talaromyces marneffei infection in a non-HIV patient.

    PubMed

    Li, H R; Xu, N L; Lin, M; Hu, X L; Chen, J H; Chen, Y S; Cai, S X

    2015-11-01

    A 57-year-old man presented with unproductive cough and dyspnea for 6 months in Fujian Province, China. His misuse of a large amount of steroids (accumulated dose equivalent to 3530 mg prednisolone) resulted in Talaromyces marneffei infection. Chest computed tomographic scan revealed diffuse interstitial and multiple cavitary lung lesions. Treatment with amphotericin B combined with itraconazole resulted in total recovery, with marked regression of lung lesions. PMID:26550481

  5. Use of an artificial neural network to predict risk factors of nosocomial infection in lung cancer patients.

    PubMed

    Chen, Jie; Pan, Qin-Shi; Hong, Wan-Dong; Pan, Jingye; Zhang, Wen-Hui; Xu, Gang; Wang, Yu-Min

    2014-01-01

    Statistical methods to analyze and predict the related risk factors of nosocomial infection in lung cancer patients are various, but the results are inconsistent. A total of 609 patients with lung cancer were enrolled to allow factor comparison using Student's t-test or the Mann-Whitney test or the Chi-square test. Variables that were significantly related to the presence of nosocomial infection were selected as candidates for input into the final ANN model. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the performance of the artificial neural network (ANN) model and logistic regression (LR) model. The prevalence of nosocomial infection from lung cancer in this entire study population was 20.1% (165/609), nosocomial infections occurring in sputum specimens (85.5%), followed by blood (6.73%), urine (6.0%) and pleural effusions (1.82%). It was shown that long term hospitalization (≥ 22 days, P= 0.000), poor clinical stage (IIIb and IV stage, P=0.002), older age (≥ 61 year old, P=0.023), and use the hormones were linked to nosocomial infection and the ANN model consisted of these four factors .The artificial neural network model with variables consisting of age, clinical stage, time of hospitalization, and use of hormones should be useful for predicting nosocomial infection in lung cancer cases.

  6. Guillain-Barré Syndrome in a Boy With Lung Fluke Infection: Case Report and Literature Review.

    PubMed

    Yang, Cui-Wei; Gao, Feng; Xia, Zhe-Zhi

    2015-08-01

    Guillain-Barré syndrome is the most common acute peripheral neuropathy in children in most countries. The cause and pathogenesis of the disease have yet to be clarified. There have been only a few reports of Guillain-Barré syndrome resulting from parasite infections worldwide, no cases of Guillain-Barré syndrome after lung fluke infection have been reported. We report a case of an 8-year-old male patient with Guillain-Barré syndrome after lung fluke infection. The child had a history of consumption of undercooked crabs. He was diagnosed with paragonimiasis. The patient experienced paralysis of and pain in the lower limbs about 3 weeks after symptom onset. Neurologic and electrophysiologic examination findings supported the diagnosis of Guillain-Barré syndrome. Parasitic infections should also be considered when determining which antecedent infection is associated with Guillain-Barré syndrome.

  7. Lung fluke (Paragonimus africanus) infects Nigerian red-capped mangabeys and causes respiratory disease

    PubMed Central

    Friant, Sagan; Brown, Kelsey; Saari, Mason T.; Segel, Nicholas H.; Slezak, Julia; Goldberg, Tony L.

    2015-01-01

    Eggs of the lung fluke genus Paragonimus were detected in red-capped mangabeys (Cercocebus torquatus) in Nigeria. We assess the role of these primates as potential sylvatic hosts and the clinical effects of the parasite on monkeys. DNA sequenced from eggs in feces were 100% identical in the ITS2 region to Paragonimus africanus sequences from humans in Cameroon. Paragonimus-positive monkeys coughed more than uninfected monkeys. Experimental de-worming led to reduction in parasite intensity and a corresponding reduction of coughing to baseline levels in infected monkeys. This report provides the first evidence of Paragonimus sp. in C. torquatus, of P. africanus in Nigerian wildlife, and the first molecular evidence of the parasite in African wildlife. Coughing, sometimes interpreted as a communication behavior in primates, can actually indicate infection with lung parasites. Observations of coughing in primates may, in turn, provide a useful mechanism for surveillance of Paragonimus spp, which are re-emerging human pathogens, in wildlife reservoirs. PMID:26543803

  8. Degradable polyphosphoester-based silver-loaded nanoparticles as therapeutics for bacterial lung infections

    NASA Astrophysics Data System (ADS)

    Zhang, Fuwu; Smolen, Justin A.; Zhang, Shiyi; Li, Richen; Shah, Parth N.; Cho, Sangho; Wang, Hai; Raymond, Jeffery E.; Cannon, Carolyn L.; Wooley, Karen L.

    2015-01-01

    In this study, a new type of degradable polyphosphoester-based polymeric nanoparticle, capable of carrying silver cations via interactions with alkyne groups, has been developed as a potentially effective and safe treatment for lung infections. It was found that up to 15% (w/w) silver loading into the nanoparticles could be achieved, consuming most of the pendant alkyne groups along the backbone, as revealed by Raman spectroscopy. The well-defined Ag-loaded nanoparticles released silver in a controlled and sustained manner over 5 days, and displayed enhanced in vitro antibacterial activities against cystic fibrosis-associated pathogens and decreased cytotoxicity to human bronchial epithelial cells, in comparison to silver acetate.In this study, a new type of degradable polyphosphoester-based polymeric nanoparticle, capable of carrying silver cations via interactions with alkyne groups, has been developed as a potentially effective and safe treatment for lung infections. It was found that up to 15% (w/w) silver loading into the nanoparticles could be achieved, consuming most of the pendant alkyne groups along the backbone, as revealed by Raman spectroscopy. The well-defined Ag-loaded nanoparticles released silver in a controlled and sustained manner over 5 days, and displayed enhanced in vitro antibacterial activities against cystic fibrosis-associated pathogens and decreased cytotoxicity to human bronchial epithelial cells, in comparison to silver acetate. Electronic supplementary information (ESI) available: Materials, experimental details, and characterization. See DOI: 10.1039/c4nr07103d

  9. Investigating the role of nucleotide-binding oligomerization domain-like receptors in bacterial lung infection.

    PubMed

    Leissinger, Mary; Kulkarni, Ritwij; Zemans, Rachel L; Downey, Gregory P; Jeyaseelan, Samithamby

    2014-06-15

    Lower respiratory tract infections (LRTIs) are a persistent and pervasive public health problem worldwide. Pneumonia and other LRTIs will be among the leading causes of death in adults, and pneumonia is the single largest cause of death in children. LRTIs are also an important cause of acute lung injury and acute exacerbations of chronic obstructive pulmonary disease. Because innate immunity is the first line of defense against pathogens, understanding the role of innate immunity in the pulmonary system is of paramount importance. Pattern recognition molecules (PRMs) that recognize microbial-associated molecular patterns are an integral component of the innate immune system and are located in both cell membranes and cytosol. Toll-like receptors and nucleotide-binding oligomerization domain-like receptors (NLRs) are the major sensors at the forefront of pathogen recognition. Although Toll-like receptors have been extensively studied in host immunity, NLRs have diverse and important roles in immune and inflammatory responses, ranging from antimicrobial properties to adaptive immune responses. The lung contains NLR-expressing immune cells such as leukocytes and nonimmune cells such as epithelial cells that are in constant and close contact with invading microbes. This pulmonary perspective addresses our current understanding of the structure and function of NLR family members, highlighting advances and gaps in knowledge, with a specific focus on immune responses in the respiratory tract during bacterial infection. Further advances in exploring cellular and molecular responses to bacterial pathogens are critical to develop improved strategies to treat and prevent devastating infectious diseases of the lung. PMID:24707903

  10. Birth weight, childhood lower respiratory tract infection, and adult lung function

    PubMed Central

    Shaheen, S; Sterne, J; Tucker, J; Florey, C

    1998-01-01

    BACKGROUND—Historical cohort studies in England have found that impaired fetal growth and lower respiratory tract infections in early childhood are associated with lower levels of lung function in late adult life. These relations are investigated in a similar study in Scotland.
METHODS—In 1985-86 a follow up study was carried out of 1070 children who had been born in St Andrew's from 1921 to 1935 and followed from birth to 14 years of age by the Mackenzie Institute for Medical Research. Recorded information included birth weight and respiratory illnesses. The lung function of 239 of these individuals was measured.
RESULTS—There was no association between birth weight and lung function. Pneumonia before two years of age was associated with a difference in mean forced expiratory volume in one second (FEV1) of −0.39 litres (95% confidence interval (CI) −0.67, −0.11; p = 0.007) and in mean forced vital capacity (FVC) of −0.60 litres (95% CI −0.92, −0.28; p<0.001), after controlling for age, sex, height, smoking, type of spirometer, and other illnesses before two years. Similar reductions were seen in men and women. Bronchitis before two years was associated with smaller deficits in FEV1 and FVC. Asthma or wheeze at two years and older and cough after five years were also associated with a reduction in FEV1.
CONCLUSIONS—The relation between impaired fetal growth and lower lung function in late adult life seen in previous studies was not confirmed in this cohort. The deficits in FEV1 and FVC associated with pneumonia and bronchitis in the first two years of life are consistent with a causal relation.

 PMID:9797752

  11. Pharmacokinetic/pharmacodynamic evaluation of sulbactam against Acinetobacter baumannii in in vitro and murine thigh and lung infection models.

    PubMed

    Yokoyama, Yuta; Matsumoto, Kazuaki; Ikawa, Kazuro; Watanabe, Erika; Shigemi, Akari; Umezaki, Yasuhiro; Nakamura, Koyo; Ueno, Keiichiro; Morikawa, Norifumi; Takeda, Yasuo

    2014-06-01

    Acinetobacter baumannii is a pathogen that has become globally associated with nosocomial infections. Sulbactam, a potent inhibitor of β-lactamases, was previously shown to be active against A. baumannii strains in vitro and effective against A. baumannii infections. However, a pharmacokinetic/pharmacodynamic (PK/PD) analysis of sulbactam against A. baumannii infections has not yet been performed. This is necessary because optimisation of dosing regimens should be based on PK/PD analysis. Therefore, in vitro and in vivo PK/PD analyses of sulbactam were performed using murine thigh and lung infection models of A. baumannii to evaluate the pharmacokinetics and pharmacodynamics of sulbactam. Sulbactam showed time-dependent bactericidal activity in vitro against A. baumannii. The PK/PD index that best correlated with its in vivo effects was the time that the free drug concentration remained above the minimum inhibitory concentration (fT>MIC) both in the thigh (R(2)=0.95) and lung (R(2)=0.96) infection models. Values of fT>MIC for a static effect and 1, 2 and 3log10 kill, respectively, were 21.0%, 32.9%, 43.6% and 57.3% in the thigh infection model and 20.4%, 24.5%, 29.3% and 37.3% in the lung infection model. Here we report the in vitro and in vivo time-dependent activities of sulbactam against A. baumannii infection and demonstrate that sulbactam was sufficiently bactericidal when an fT>MIC of >60% against A. baumannii thigh infection and >40% against A. baumannii lung infection was achieved.

  12. A role for Toll-like receptor 4 in the host response to the lung infection of Yersinia pseudotuberculosis in mice.

    PubMed

    Choi, Jin-A; Jeong, Yu-Jin; Kim, Jae-Eun; Kang, Min-Jung; Kim, Jee-Cheon; Oh, Sang-Muk; Lee, Kyung-Bok; Kim, Dong-Hyun; Kim, Dong-Jae; Park, Jong-Hwan

    2016-02-01

    Although a Yersinia pseudotuberculosis (Yptb) lung infection model has been developed to study Y. pestis pathogenesis, it is still necessary to establish a new animal model to mimic the pathophysiological features induced by Y. pestis infection. Here, we provide a new lung infection model using the Yptb strain, IP2777, which displayed rapid spread of bacteria to the liver, spleen, and blood. In addition, we examined whether TLR4 is involved in Yptb-induced pathogenesis in the lung infection model of mice we generated. Following lung infection of WT and TLR4-deficient mice with the Yptb strain IP2777, the survival rate, bacterial colonization, histopathology, and level of cytokines and chemokines in the lung, spleen, liver, and blood were analyzed. TLR4-deficient mice had a lower survival rate than WT mice in response to Yptb lung infection. Although the bacterial colonization and pathology of the lung were comparable between WT and TLR4-deficient mice, those of the spleen and liver were more severe in TLR4-deficient mice. In addition, the levels of TNF-α and CXCL2 in the liver and IL-6 and CXCL2 in the blood were higher in TLR4-deficient mice than in WT mice. Our results demonstrate that TLR4 is necessary for optimal host protection against Yptb lung infection and TLR4-deficient mice may serve as a better genetic model of Yptb infection for mimicking Y. pestis infection. PMID:26851596

  13. Direct observation of phagocytosis and NET-formation by neutrophils in infected lungs using 2-photon microscopy.

    PubMed

    Hasenberg, Mike; Köhler, Anja; Bonifatius, Susanne; Jeron, Andreas; Gunzer, Matthias

    2011-06-02

    After the gastrointestinal tract, the lung is the second largest surface for interaction between the vertebrate body and the environment. Here, an effective gas exchange must be maintained, while at the same time avoiding infection by the multiple pathogens that are inhaled during normal breathing. To achieve this, a superb set of defense strategies combining humoral and cellular immune mechanisms exists. One of the most effective measures for acute defense of the lung is the recruitment of neutrophils, which either phagocytose the inhaled pathogens or kill them by releasing cytotoxic chemicals. A recent addition to the arsenal of neutrophils is their explosive release of extracellular DNA-NETs by which bacteria or fungi can be caught or inactivated even after the NET releasing cells have died. We present here a method that allows one to directly observe neutrophils, migrating within a recently infected lung, phagocytosing fungal pathogens as well as visualize the extensive NETs that they have produced throughout the infected tissue. The method describes the preparation of thick viable lung slices 7 hours after intratracheal infection of mice with conidia of the mold Aspergillus fumigatus and their examination by multicolor time-lapse 2-photon microscopy. This approach allows one to directly investigate antifungal defense in native lung tissue and thus opens a new avenue for the detailed investigation of pulmonary immunity.

  14. Dermatoses associated with mites other than Sarcoptes.

    PubMed

    Ken, Kimberly M; Shockman, Solomon C; Sirichotiratana, Melissa; Lent, Megan P; Wilson, Morgan L

    2014-09-01

    Mites are arthropods of the subclass Acari (Acarina). Although Sarcoptes is the mite most commonly recognized as a cause of human skin disease in the United States, numerous other mite-associated dermatoses have been described, and merit familiarity on the part of physicians treating skin disease. This review discusses several non-scabies mites and their associated diseases, including Demodex, chiggers, Cheyletiella, bird mites, grain itch, oak leaf itch, grocer's itch, tropical rat mite, snake mite, and Psoroptes. PMID:25577848

  15. Acanthamoeba infection in lungs of mice expressed by toll-like receptors (TLR2 and TLR4).

    PubMed

    Derda, Monika; Wojtkowiak-Giera, Agnieszka; Kolasa-Wołosiuk, Agnieszka; Kosik-Bogacka, Danuta; Hadaś, Edward; Jagodziński, Paweł P; Wandurska-Nowak, Elżbieta

    2016-06-01

    Toll-like receptors (TLRs) play a key role in the innate immune responses to a variety of pathogens including parasites. TLRs are among the most highly conserved in the evolution of the receptor family, localized mainly on cells of the immune system and on other cells such as lung cells. The aim of this study was to determine for the first time the expression of TLR2 and TLR4 in the lung of Acanthamoeba spp. infected mice using quantitative real-time polymerase chain reaction (Q-PCR) and immunohistochemical (IHC) staining. The Acanthamoeba spp. were isolated from a patient with Acanthamoeba keratitis (AK) (strain Ac 55) and from environmental samples of water from Malta Lake (Poznań, Poland - strain Ac 43). We observed a significantly increased level of expression of TLR2 as well as TLR4 mRNA from 2 to 30 days post Acanthamoeba infection (dpi) in the lungs of mice infected with Ac55 (KP120880) and Ac43 (KP120879) strains. According to our observations, increased TLR2 and TLR4 expression in the pneumocytes, interstitial cells and epithelial cells of the bronchial tree may suggest an important role of these receptors in protective immunity against Acanthamoeba infection in the lung. Moreover, increased levels of TLR2 and TLR4 mRNA expression in infected Acanthamoeba mice may suggest the involvement of these TLRs in the recognition of this amoeba pathogen-associated molecular pattern (PAMP). PMID:26940205

  16. Stereological analysis of bacterial load and lung lesions in nonhuman primates (rhesus macaques) experimentally infected with Mycobacterium tuberculosis

    PubMed Central

    Oslund, Karen L.; Yang, Xiao-wei; Adamson, Lourdes; Ravindran, Resmi; Canfield, Don R.; Tarara, Ross; Hirst, Linda; Christensen, Miles; Lerche, Nicholas W.; Offenstein, Heather; Lewinsohn, David; Ventimiglia, Frank; Brignolo, Laurie; Wisner, Erik R.; Hyde, Dallas M.

    2011-01-01

    Infection with Mycobacterium tuberculosis primarily produces a multifocal distribution of pulmonary granulomas in which the pathogen resides. Accordingly, quantitative assessment of the bacterial load and pathology is a substantial challenge in tuberculosis. Such assessments are critical for studies of the pathogenesis and for the development of vaccines and drugs in animal models of experimental M. tuberculosis infection. Stereology enables unbiased quantitation of three-dimensional objects from two-dimensional sections and thus is suited to quantify histological lesions. We have developed a protocol for stereological analysis of the lung in rhesus macaques inoculated with a pathogenic clinical strain of M. tuberculosis (Erdman strain). These animals exhibit a pattern of infection and tuberculosis similar to that of naturally infected humans. Conditions were optimized for collecting lung samples in a nonbiased, random manner. Bacterial load in these samples was assessed by a standard plating assay, and granulomas were graded and enumerated microscopically. Stereological analysis provided quantitative data that supported a significant correlation between bacterial load and lung granulomas. Thus this stereological approach enables a quantitative, statistically valid analysis of the impact of M. tuberculosis infection in the lung and will serve as an essential tool for objectively comparing the efficacy of drugs and vaccines. PMID:21873450

  17. Acanthamoeba infection in lungs of mice expressed by toll-like receptors (TLR2 and TLR4).

    PubMed

    Derda, Monika; Wojtkowiak-Giera, Agnieszka; Kolasa-Wołosiuk, Agnieszka; Kosik-Bogacka, Danuta; Hadaś, Edward; Jagodziński, Paweł P; Wandurska-Nowak, Elżbieta

    2016-06-01

    Toll-like receptors (TLRs) play a key role in the innate immune responses to a variety of pathogens including parasites. TLRs are among the most highly conserved in the evolution of the receptor family, localized mainly on cells of the immune system and on other cells such as lung cells. The aim of this study was to determine for the first time the expression of TLR2 and TLR4 in the lung of Acanthamoeba spp. infected mice using quantitative real-time polymerase chain reaction (Q-PCR) and immunohistochemical (IHC) staining. The Acanthamoeba spp. were isolated from a patient with Acanthamoeba keratitis (AK) (strain Ac 55) and from environmental samples of water from Malta Lake (Poznań, Poland - strain Ac 43). We observed a significantly increased level of expression of TLR2 as well as TLR4 mRNA from 2 to 30 days post Acanthamoeba infection (dpi) in the lungs of mice infected with Ac55 (KP120880) and Ac43 (KP120879) strains. According to our observations, increased TLR2 and TLR4 expression in the pneumocytes, interstitial cells and epithelial cells of the bronchial tree may suggest an important role of these receptors in protective immunity against Acanthamoeba infection in the lung. Moreover, increased levels of TLR2 and TLR4 mRNA expression in infected Acanthamoeba mice may suggest the involvement of these TLRs in the recognition of this amoeba pathogen-associated molecular pattern (PAMP).

  18. Plasminogen activator inhibitor-1 in cigarette smoke exposure and influenza A virus infection-induced lung injury.

    PubMed

    Bhandary, Yashodhar P; Shetty, Shwetha K; Marudamuthu, Amarnath S; Midde, Krishna K; Ji, Hong-Long; Shams, Homoyoun; Subramaniam, Renuka; Fu, Jian; Idell, Steven; Shetty, Sreerama

    2015-01-01

    Parenchymal lung inflammation and airway and alveolar epithelial cell apoptosis are associated with cigarette smoke exposure (CSE), which contributes to chronic obstructive pulmonary disease (COPD). Epidemiological studies indicate that people exposed to chronic cigarette smoke with or without COPD are more susceptible to influenza A virus (IAV) infection. We found increased p53, PAI-1 and apoptosis in AECs, with accumulation of macrophages and neutrophils in the lungs of patients with COPD. In Wild-type (WT) mice with passive CSE (PCSE), p53 and PAI-1 expression and apoptosis were increased in AECs as was lung inflammation, while those lacking p53 or PAI-1 resisted AEC apoptosis and lung inflammation. Further, inhibition of p53-mediated induction of PAI-1 by treatment of WT mice with caveolin-1 scaffolding domain peptide (CSP) reduced PCSE-induced lung inflammation and reversed PCSE-induced suppression of eosinophil-associated RNase1 (EAR1). Competitive inhibition of the p53-PAI-1 mRNA interaction by expressing p53-binding 3'UTR sequences of PAI-1 mRNA likewise suppressed CS-induced PAI-1 and AEC apoptosis and restored EAR1 expression. Consistent with PCSE-induced lung injury, IAV infection increased p53, PAI-1 and apoptosis in AECs in association with pulmonary inflammation. Lung inflammation induced by PCSE was worsened by subsequent exposure to IAV. Mice lacking PAI-1 that were exposed to IAV showed minimal viral burden based on M2 antigen and hemagglutination analyses, whereas transgenic mice that overexpress PAI-1 without PCSE showed increased M2 antigen and inflammation after IAV infection. These observations indicate that increased PAI-1 expression promotes AEC apoptosis and exacerbates lung inflammation induced by IAV following PCSE.

  19. Plasminogen Activator Inhibitor-1 in Cigarette Smoke Exposure and Influenza A Virus Infection-Induced Lung Injury

    PubMed Central

    Bhandary, Yashodhar P.; Shetty, Shwetha K.; Marudamuthu, Amarnath S.; Midde, Krishna K.; Ji, Hong-Long; Shams, Homoyoun; Subramaniam, Renuka; Fu, Jian; Idell, Steven; Shetty, Sreerama

    2015-01-01

    Parenchymal lung inflammation and airway and alveolar epithelial cell apoptosis are associated with cigarette smoke exposure (CSE), which contributes to chronic obstructive pulmonary disease (COPD). Epidemiological studies indicate that people exposed to chronic cigarette smoke with or without COPD are more susceptible to influenza A virus (IAV) infection. We found increased p53, PAI-1 and apoptosis in AECs, with accumulation of macrophages and neutrophils in the lungs of patients with COPD. In Wild-type (WT) mice with passive CSE (PCSE), p53 and PAI-1 expression and apoptosis were increased in AECs as was lung inflammation, while those lacking p53 or PAI-1 resisted AEC apoptosis and lung inflammation. Further, inhibition of p53-mediated induction of PAI-1 by treatment of WT mice with caveolin-1 scaffolding domain peptide (CSP) reduced PCSE-induced lung inflammation and reversed PCSE-induced suppression of eosinophil-associated RNase1 (EAR1). Competitive inhibition of the p53-PAI-1 mRNA interaction by expressing p53-binding 3’UTR sequences of PAI-1 mRNA likewise suppressed CS-induced PAI-1 and AEC apoptosis and restored EAR1 expression. Consistent with PCSE-induced lung injury, IAV infection increased p53, PAI-1 and apoptosis in AECs in association with pulmonary inflammation. Lung inflammation induced by PCSE was worsened by subsequent exposure to IAV. Mice lacking PAI-1 that were exposed to IAV showed minimal viral burden based on M2 antigen and hemagglutination analyses, whereas transgenic mice that overexpress PAI-1 without PCSE showed increased M2 antigen and inflammation after IAV infection. These observations indicate that increased PAI-1 expression promotes AEC apoptosis and exacerbates lung inflammation induced by IAV following PCSE. PMID:25932922

  20. Acaroid mite, intestinal and urinary acariasis

    PubMed Central

    Li, Chao-Pin; Cui, Yu-Bao; Wang, Jian; Yang, Qing-Gui; Tian, Ye

    2003-01-01

    significant difference was found among the frequencies of mite infection in individuals with different occupations (χ2 = 82.55, P < 0.001), with its frequencies in those working in medicinal herb storehouses, those in rice storehouse or mills, miners, railway workers, pupils and teachers being 15.89% (68/428), 12.96% (53/409), 3.28% (18/549), 2.54% (6/236), 5.10% (13/255) and 2.56% (3/117), respectively. CONCLUSION: The prevalence of human intestinal and urinary acariasis was not associated with gender, and these diseases are more frequently found in individuals working in medicinal herb, rice storehouses or mills and other sites with high density of mites. More attention should be paid to the mite prevention and labor protection for these high-risk groups. PMID:12679953

  1. Importance of bacterial replication and alveolar macrophage-independent clearance mechanisms during early lung infection with Streptococcus pneumoniae.

    PubMed

    Camberlein, Emilie; Cohen, Jonathan M; José, Ricardo; Hyams, Catherine J; Callard, Robin; Chimalapati, Suneeta; Yuste, Jose; Edwards, Lindsey A; Marshall, Helina; van Rooijen, Nico; Noursadeghi, Mahdad; Brown, Jeremy S

    2015-03-01

    Although the importance of alveolar macrophages for host immunity during early Streptococcus pneumoniae lung infection is well established, the contribution and relative importance of other innate immunity mechanisms and of bacterial factors are less clear. We have used a murine model of S. pneumoniae early lung infection with wild-type, unencapsulated, and para-amino benzoic acid auxotroph mutant TIGR4 strains to assess the effects of inoculum size, bacterial replication, capsule, and alveolar macrophage-dependent and -independent clearance mechanisms on bacterial persistence within the lungs. Alveolar macrophage-dependent and -independent (calculated indirectly) clearance half-lives and bacterial replication doubling times were estimated using a mathematical model. In this model, after infection with a high-dose inoculum of encapsulated S. pneumoniae, alveolar macrophage-independent clearance mechanisms were dominant, with a clearance half-life of 24 min compared to 135 min for alveolar macrophage-dependent clearance. In addition, after a high-dose inoculum, successful lung infection required rapid bacterial replication, with an estimated S. pneumoniae doubling time of 16 min. The capsule had wide effects on early lung clearance mechanisms, with reduced half-lives of 14 min for alveolar macrophage-independent and 31 min for alveolar macrophage-dependent clearance of unencapsulated bacteria. In contrast, with a lower-dose inoculum, the bacterial doubling time increased to 56 min and the S. pneumoniae alveolar macrophage-dependent clearance half-life improved to 42 min and was largely unaffected by the capsule. These data demonstrate the large effects of bacterial factors (inoculum size, the capsule, and rapid replication) and alveolar macrophage-independent clearance mechanisms during early lung infection with S. pneumoniae. PMID:25583525

  2. Importance of bacterial replication and alveolar macrophage-independent clearance mechanisms during early lung infection with Streptococcus pneumoniae.

    PubMed

    Camberlein, Emilie; Cohen, Jonathan M; José, Ricardo; Hyams, Catherine J; Callard, Robin; Chimalapati, Suneeta; Yuste, Jose; Edwards, Lindsey A; Marshall, Helina; van Rooijen, Nico; Noursadeghi, Mahdad; Brown, Jeremy S

    2015-03-01

    Although the importance of alveolar macrophages for host immunity during early Streptococcus pneumoniae lung infection is well established, the contribution and relative importance of other innate immunity mechanisms and of bacterial factors are less clear. We have used a murine model of S. pneumoniae early lung infection with wild-type, unencapsulated, and para-amino benzoic acid auxotroph mutant TIGR4 strains to assess the effects of inoculum size, bacterial replication, capsule, and alveolar macrophage-dependent and -independent clearance mechanisms on bacterial persistence within the lungs. Alveolar macrophage-dependent and -independent (calculated indirectly) clearance half-lives and bacterial replication doubling times were estimated using a mathematical model. In this model, after infection with a high-dose inoculum of encapsulated S. pneumoniae, alveolar macrophage-independent clearance mechanisms were dominant, with a clearance half-life of 24 min compared to 135 min for alveolar macrophage-dependent clearance. In addition, after a high-dose inoculum, successful lung infection required rapid bacterial replication, with an estimated S. pneumoniae doubling time of 16 min. The capsule had wide effects on early lung clearance mechanisms, with reduced half-lives of 14 min for alveolar macrophage-independent and 31 min for alveolar macrophage-dependent clearance of unencapsulated bacteria. In contrast, with a lower-dose inoculum, the bacterial doubling time increased to 56 min and the S. pneumoniae alveolar macrophage-dependent clearance half-life improved to 42 min and was largely unaffected by the capsule. These data demonstrate the large effects of bacterial factors (inoculum size, the capsule, and rapid replication) and alveolar macrophage-independent clearance mechanisms during early lung infection with S. pneumoniae.

  3. [House dust mite allergy].

    PubMed

    Carrard, A; Pichler, C

    2012-04-01

    House dust mites can be found all over the world where human beings live independent from the climate. Proteins from the gastrointestinal tract- almost all known as enzymes - are the allergens which induce chronic allergic diseases. The inhalation of small amounts of allergens on a regular base all night leads to a slow beginning of the disease with chronically stuffed nose and an exercise induced asthma which later on persists. House dust mites grow well in a humid climate - this can be in well isolated dwellings or in the tropical climate - and nourish from human skin dander. Scales are found in mattresses, upholstered furniture and carpets. The clinical picture with slowly aggravating complaints leads quite often to a delayed diagnosis, which is accidently done on the occasion of a wider spectrum of allergy skin testing. The beginning of a medical therapy with topical steroids as nasal spray or inhalation leads to a fast relief of the complaints. Although discussed in extensive controversies in the literature - at least in Switzerland with the cold winter and dry climate - the recommendation of house dust mite avoidance measures is given to patients with good clinical results. The frequent ventilation of the dwelling with cold air in winter time cause a lower indoor humidity. Covering encasings on mattresses, pillow, and duvets reduces the possibility of chronic contact with mite allergens as well as the weekly changing the bed linen. Another option of therapy is the specific immunotherapy with extracts of house dust mites showing good results in children and adults. Using recombinant allergens will show a better quality in diagnostic as well as in therapeutic specific immunotherapy. PMID:22477664

  4. [House dust mite allergy].

    PubMed

    Carrard, A; Pichler, C

    2012-04-01

    House dust mites can be found all over the world where human beings live independent from the climate. Proteins from the gastrointestinal tract- almost all known as enzymes - are the allergens which induce chronic allergic diseases. The inhalation of small amounts of allergens on a regular base all night leads to a slow beginning of the disease with chronically stuffed nose and an exercise induced asthma which later on persists. House dust mites grow well in a humid climate - this can be in well isolated dwellings or in the tropical climate - and nourish from human skin dander. Scales are found in mattresses, upholstered furniture and carpets. The clinical picture with slowly aggravating complaints leads quite often to a delayed diagnosis, which is accidently done on the occasion of a wider spectrum of allergy skin testing. The beginning of a medical therapy with topical steroids as nasal spray or inhalation leads to a fast relief of the complaints. Although discussed in extensive controversies in the literature - at least in Switzerland with the cold winter and dry climate - the recommendation of house dust mite avoidance measures is given to patients with good clinical results. The frequent ventilation of the dwelling with cold air in winter time cause a lower indoor humidity. Covering encasings on mattresses, pillow, and duvets reduces the possibility of chronic contact with mite allergens as well as the weekly changing the bed linen. Another option of therapy is the specific immunotherapy with extracts of house dust mites showing good results in children and adults. Using recombinant allergens will show a better quality in diagnostic as well as in therapeutic specific immunotherapy.

  5. Cigarette Smoke Exposure Exacerbates Lung Inflammation and Compromises Immunity to Bacterial Infection

    PubMed Central

    Lugade, Amit A.; Bogner, Paul N.; Thatcher, Thomas H.; Sime, Patricia J.; Phipps, Richard P.; Thanavala, Yasmin

    2014-01-01

    The detrimental impact of tobacco on human health is clearly recognized and despite aggressive efforts to prevent smoking, close to one billion individuals worldwide continue to smoke. People with chronic obstructive pulmonary disease (COPD) are susceptible to recurrent respiratory infections with pathogens, including non-typeable Haemophilus influenzae (NTHI), yet the reasons for this increased susceptibility are poorly understood. As mortality rapidly increases with multiple exacerbations, development of protective immunity is critical to improving patient survival. Acute NTHI infection has been studied in the context of cigarette smoke exposure, but this is the first study to investigate chronic infection and the generation of adaptive immune responses to NTHI following chronic smoke exposure. After chronic NTHI infection, mice that had previously been exposed to cigarette smoke developed increased lung inflammation and compromised adaptive immunity relative to air-exposed controls. Importantly, NTHI-specific T cells from mice exposed to cigarette smoke produced lower levels of IFN-γ and IL-4, and B cells produced reduced levels of antibodies against outer membrane lipoprotein P6, with impaired IgG1, IgG2a and IgA class-switching. However, production of IL-17, which is associated with neutrophilic inflammation, was enhanced. Interestingly, cigarette smoke exposed mice exhibited a similar defect in the generation of adaptive immunity following immunization with P6. Our study has conclusively demonstrated that cigarette smoke exposure has a profound suppressive effect on the generation of adaptive immune responses to NTHI and suggests the mechanism by which prior cigarette smoke exposure predisposes COPD patients to recurrent infections, leading to exacerbations and contributing to mortality. PMID:24752444

  6. Fatal Scopulariopsis Infection in a Lung Transplant Recipient: Lessons of Organ Procurement

    PubMed Central

    Shaver, C. M.; Castilho, J. L.; Cohen, D. N.; Grogan, E. L.; Miller, G. G.; Dummer, J. S.; Gray, J.N.; Lambright, E. S.; Loyd, J.E.; Robbins, I. M.

    2014-01-01

    Seventeen days after double lung transplantation, a 56-year-old patient with idiopathic pulmonary fibrosis developed respiratory distress. Imaging revealed bilateral pulmonary infiltrates with pleural effusions and physical examination demonstrated sternal instability. Broad-spectrum antibacterial and antifungal therapy was initiated and bilateral thoracotomy tubes were placed. Both right and left pleural cultures grew a mold subsequently identified as Scopulariopsis brumptii. The patient underwent pleural irrigation and sternal debridement three times but pleural and wound cultures continued to grow S. brumptii. Despite treatment with five antifungal agents, the patient succumbed to his illness sixty-seven days after transplantation. Autopsy confirmed the presence of markedly invasive fungal disease and pleural rind formation. The patient’s organ donor had received bilateral thoracostomy tubes during resuscitation in a wilderness location. There were no visible pleural abnormalities at the time of transplantation. However, the patient’s clinical course and the location of the infection, in addition to the lack of similar infection in other organ recipients, strongly suggest that Scopulariopsis was introduced into the pleural space during pre-hospital placement of thoracostomy tubes. This case of lethal infection transmitted through transplantation highlights the unique risk of using organs from donors who are resuscitated in an outdoor location. PMID:25376207

  7. Ear Mite Removal in the Santa Catalina Island Fox (Urocyon littoralis catalinae): Controlling Risk Factors for Cancer Development

    PubMed Central

    Moriarty, Megan E.; Vickers, T. Winston; Clifford, Deana L.; Garcelon, David K.; Gaffney, Patricia M.; Lee, Kenneth W.; King, Julie L.; Duncan, Calvin L.; Boyce, Walter M.

    2015-01-01

    Ear mites (Otodectes cynotis) and ear canal tumors are highly prevalent among federally endangered Island foxes (Urocyon littoralis catalinae) living on Santa Catalina Island off the coast of Southern California. Since studies began in the 1990s, nearly all foxes examined were found to be infected with ear mites, and ceruminous gland tumors (carcinomas and adenomas) were detected in approximately half of all foxes ≥ 4 years of age. We hypothesized that reduction of ear mite infection would reduce otitis externa and ceruminous gland hyperplasia, a risk factor for tumor development. In this study, we conducted a randomized field trial to assess the impact of acaricide treatment on ear mite prevalence and intensity of infection, otitis externa, ceruminous gland hyperplasia, and mite-specific IgG and IgE antibody levels. Treatment was highly effective at eliminating mites and reducing otitis externa and ceruminous gland hyperplasia, and mite-specific IgG antibody levels were significantly lower among uninfected foxes. Ceruminous gland hyperplasia increased in the chronically infected, untreated foxes during the six month study. Our results provide compelling evidence that acaricide treatment is an effective means of reducing ear mites, and that mite removal in turn reduces ear lesions and mite-specific IgG antibody levels in Santa Catalina Island foxes. This study has advanced our understanding of the underlying pathogenesis which results in ceruminous gland tumors, and has helped inform management decisions that impact species conservation. PMID:26641820

  8. Ear Mite Removal in the Santa Catalina Island Fox (Urocyon littoralis catalinae): Controlling Risk Factors for Cancer Development.

    PubMed

    Moriarty, Megan E; Vickers, T Winston; Clifford, Deana L; Garcelon, David K; Gaffney, Patricia M; Lee, Kenneth W; King, Julie L; Duncan, Calvin L; Boyce, Walter M

    2015-01-01

    Ear mites (Otodectes cynotis) and ear canal tumors are highly prevalent among federally endangered Island foxes (Urocyon littoralis catalinae) living on Santa Catalina Island off the coast of Southern California. Since studies began in the 1990s, nearly all foxes examined were found to be infected with ear mites, and ceruminous gland tumors (carcinomas and adenomas) were detected in approximately half of all foxes ≥ 4 years of age. We hypothesized that reduction of ear mite infection would reduce otitis externa and ceruminous gland hyperplasia, a risk factor for tumor development. In this study, we conducted a randomized field trial to assess the impact of acaricide treatment on ear mite prevalence and intensity of infection, otitis externa, ceruminous gland hyperplasia, and mite-specific IgG and IgE antibody levels. Treatment was highly effective at eliminating mites and reducing otitis externa and ceruminous gland hyperplasia, and mite-specific IgG antibody levels were significantly lower among uninfected foxes. Ceruminous gland hyperplasia increased in the chronically infected, untreated foxes during the six month study. Our results provide compelling evidence that acaricide treatment is an effective means of reducing ear mites, and that mite removal in turn reduces ear lesions and mite-specific IgG antibody levels in Santa Catalina Island foxes. This study has advanced our understanding of the underlying pathogenesis which results in ceruminous gland tumors, and has helped inform management decisions that impact species conservation. PMID:26641820

  9. [Host selection of ectoparasitic gamasid mites on Tylonycteris pachypus and T. robustula].

    PubMed

    Zhang, Guang-Liang; Tang, Zhan-Hui; Hong, Ti-Yu; Yang, Jian; Zeng, Yu; Tan, Liang-Jing; Liu, Qi; Chen, Yi; Shen, Qi-Qi; Zhang, Li-Biao

    2013-02-01

    Correlations of two species of gamasid mites (Macronyssus pararadovskyi and M. radovskyi) and their bat hosts (Tylonycteris pachypus and T. robustula) were studied by field surveys and indoor behavioral experiments. The wild data indicated that mite load was positively correlated with body condition index of female T. pachypus hosts (Spearman: r (s)=0.55, P<0.01, n=24). Whereas, mite loads had no correlation with body condition indexes of male T. pachypus and all T. robustula hosts (P>0.05). Indoor original host infection showed that mites preferred male T. pachypus and T. robustula hosts. The infection percentages on male hosts were significantly higher than those on female hosts [T. pachypus: male (58±12)%, female (42±12)%, (t=-3.6, df=31, P<0.01); T. robustula: male (63±11)%, female (37±11)%, (t=-6.1, df=26, P<0.001)]. Using M. pararadovskyi (original host T. pachypus) to across infect T. pachypus and T. robustula, we found that mites significantly preferred the original host (t=9.1, df=29, P<0.001). The infection percentages of T. pachypus, and T. robustula were (71±13)% and (29±13)%, respectively. Our results indicated that mite loads of the two bat species were not correlated with body condition indexes of hosts. However, these mites presented different host sexual preferences, and the mites of T. pachypus presented specific host species preferences.

  10. [Experimental study of the inoculative transmission of Rickettsia typhi by gamasid mites (Gamasidae) Ornithonyssus bacoti].

    PubMed

    Grabarev, P A; Suroviatkin, A V; Tikhonova, Iu Iu; Mishchenko, O A; Potapenko, O V

    2009-01-01

    The authors' studies have established that the concentration of Rickettsia typhi may increase about 100-fold in the infected Ornithonyssus bacoti mites. At the time, when on feeding 20 to 200 adult mites on guinea-pigs and albino rats 4 to 36 days after inoculation, they did not transmit Rickettsia typhi on blood sucking. PMID:19566066

  11. Degradable polyphosphoester-based silver-loaded nanoparticles as therapeutics for bacterial lung infections.

    PubMed

    Zhang, Fuwu; Smolen, Justin A; Zhang, Shiyi; Li, Richen; Shah, Parth N; Cho, Sangho; Wang, Hai; Raymond, Jeffery E; Cannon, Carolyn L; Wooley, Karen L

    2015-02-14

    In this study, a new type of degradable polyphosphoester-based polymeric nanoparticle, capable of carrying silver cations via interactions with alkyne groups, has been developed as a potentially effective and safe treatment for lung infections. It was found that up to 15% (w/w) silver loading into the nanoparticles could be achieved, consuming most of the pendant alkyne groups along the backbone, as revealed by Raman spectroscopy. The well-defined Ag-loaded nanoparticles released silver in a controlled and sustained manner over 5 days, and displayed enhanced in vitro antibacterial activities against cystic fibrosis-associated pathogens and decreased cytotoxicity to human bronchial epithelial cells, in comparison to silver acetate. PMID:25573163

  12. Low-Dose Intestinal Trichuris muris Infection Alters the Lung Immune Microenvironment and Can Suppress Allergic Airway Inflammation.

    PubMed

    Chenery, Alistair L; Antignano, Frann; Burrows, Kyle; Scheer, Sebastian; Perona-Wright, Georgia; Zaph, Colby

    2015-12-07

    Immunological cross talk between mucosal tissues such as the intestine and the lung is poorly defined during homeostasis and disease. Here, we show that a low-dose infection with the intestinally restricted helminth parasite Trichuris muris results in the production of Th1 cell-dependent gamma interferon (IFN-γ) and myeloid cell-derived interleukin-10 (IL-10) in the lung without causing overt airway pathology. This cross-mucosal immune response in the lung inhibits the development of papain-induced allergic airway inflammation, an innate cell-mediated type 2 airway inflammatory disease. Thus, we identify convergent and nonredundant roles of adaptive and innate immunity in mediating cross-mucosal suppression of type 2 airway inflammation during low-dose helminth-induced intestinal inflammation. These results provide further insight in identifying novel intersecting immune pathways elicited by gut-to-lung mucosal cross talk.

  13. Low-Dose Intestinal Trichuris muris Infection Alters the Lung Immune Microenvironment and Can Suppress Allergic Airway Inflammation.

    PubMed

    Chenery, Alistair L; Antignano, Frann; Burrows, Kyle; Scheer, Sebastian; Perona-Wright, Georgia; Zaph, Colby

    2016-02-01

    Immunological cross talk between mucosal tissues such as the intestine and the lung is poorly defined during homeostasis and disease. Here, we show that a low-dose infection with the intestinally restricted helminth parasite Trichuris muris results in the production of Th1 cell-dependent gamma interferon (IFN-γ) and myeloid cell-derived interleukin-10 (IL-10) in the lung without causing overt airway pathology. This cross-mucosal immune response in the lung inhibits the development of papain-induced allergic airway inflammation, an innate cell-mediated type 2 airway inflammatory disease. Thus, we identify convergent and nonredundant roles of adaptive and innate immunity in mediating cross-mucosal suppression of type 2 airway inflammation during low-dose helminth-induced intestinal inflammation. These results provide further insight in identifying novel intersecting immune pathways elicited by gut-to-lung mucosal cross talk. PMID:26644379

  14. Nano-antibiotics in chronic lung infection therapy against Pseudomonas aeruginosa.

    PubMed

    Hadinoto, Kunn; Cheow, Wean Sin

    2014-04-01

    Antibiotic encapsulation into nanoparticle carriers has emerged as a promising inhaled antibiotic formulation for treatment of chronic Pseudomonas aeruginosa lung infection prevalent in chronic obstructive pulmonary diseases. Attributed to their prolonged lung retention, sustained antibiotic release, and mucus penetrating ability, antibiotic nanoparticles, or nano-antibiotics in short, can address the principal weakness of inhaled antibiotic solution, i.e. low antibiotic exposure in the vicinity of P. aeruginosa biofilm colonies resulting in diminished anti-pseudomonal efficacy after repeated uses. This review details the current state of development and limitations of the two most widely studied forms of nano-antibiotics, i.e. liposomes and polymer nanoparticles. Factors in their formulation that influence the anti-pseudomonal efficacy in vitro and in vivo, such as liposome's membrane rigidity, surface charge, size, and polymer hydrophobicity, are discussed. This review reveals that the superior anti-pseudomonal efficacy of liposomal antibiotics to free antibiotics has been clearly established when they are correctly formulated, with several liposomal antibiotic formulations are currently undergoing clinical trials. Liposomal antibiotics, nevertheless, are not without limitation due to their weak physicochemical stability. In contrast, only mucus penetrating ability of the more stable polymeric nano-antibiotics has been established, while their anti-pseudomonal efficacy has only been examined in vitro from which their superiority to free antibiotics has not been ascertained. Lastly, future research needs to bring liposome and polymer-based nano-antibiotics closer to their clinical realization are identified.

  15. Type I interferons induce lung protease responses following respiratory syncytial virus infection via RIG-I-like receptors

    PubMed Central

    Foronjy, Robert F.; Taggart, Clifford C.; Dabo, Abdoulaye J.; Weldon, Sinéad; Cummins, Neville; Geraghty, Patrick

    2014-01-01

    The role of proteases in viral infection of the lung is poorly understood. Thus, we examined MMP and cathepsin proteases in respiratory syncytial virus (RSV) infected mouse lungs. RSV induced gene expression for matrix metalloproteinases (MMP) -2, -3, -7, -8, -9, -10, -12, -13, -14, -16, -17, -19, -20, -25, -27, -28 and cathepsins B, C, E, G, H, K, L1, S, W and Z in the airways of FVB/NJ mice. Increased proteases were present in the bronchoalveolar lavage fluid (BALF) and lung tissue during infection. Mitochondrial antiviral-signaling protein (Mavs) and Trif deficient mice were exposed to RSV. Mavs deficient mice had significantly lower expression of airway MMP-2, -3, -7, -8, -9, -10, -12, -13 and -28 and cathepsins C, G, K, S, W and Z. In lung epithelial cells, retinoic acid–inducible gene-1 (RIG-I) was identified as the major RIG-I- like receptor (RLR) required for RSV induced protease expression via MAVS. Overexpression of RIG-I or treatment with IFN-β in these cells induced MMP and cathepsin gene and protein expression. The significance of RIG-1 protease induction was demonstrated by the fact that inhibiting proteases with batimastat, E64 or ribavirin prevented airway hyperresponsiveness and enhanced viral clearance in RSV infected mice. PMID:25005357

  16. Interleukin-10 plays a key role in the modulation of neutrophils recruitment and lung inflammation during infection by Streptococcus pneumoniae.

    PubMed

    Peñaloza, Hernán F; Nieto, Pamela A; Muñoz-Durango, Natalia; Salazar-Echegarai, Francisco J; Torres, Javiera; Parga, María J; Alvarez-Lobos, Manuel; Riedel, Claudia A; Kalergis, Alexis M; Bueno, Susan M

    2015-09-01

    Streptococcus pneumoniae is a major aetiological agent of pneumonia worldwide, as well as otitis media, sinusitis, meningitis and sepsis. Recent reports have suggested that inflammation of lungs due to S. pneumoniae infection promotes bacterial dissemination and severe disease. However, the contribution of anti-inflammatory molecules to the pathogenesis of S. pneumoniae remains unknown. To elucidate whether the production of the anti-inflammatory cytokine interleukin-10 (IL-10) is beneficial or detrimental for the host during pneumococcal pneumonia, we performed S. pneumoniae infections in mice lacking IL-10 (IL-10(-/-) mice). The IL-10(-/-) mice showed increased mortality, higher expression of pro-inflammatory cytokines, and an exacerbated recruitment of neutrophils into the lungs after S. pneumoniae infection. However, IL-10(-/-) mice showed significantly lower bacterial loads in lungs, spleen, brain and blood, when compared with mice that produced this cytokine. Our results support the notion that production of IL-10 during S. pneumoniae infection modulates the expression of pro-inflammatory cytokines and the infiltration of neutrophils into the lungs. This feature of IL-10 is important to avoid excessive inflammation of tissues and to improve host survival, even though bacterial dissemination is less efficient in the absence of this cytokine.

  17. Interleukin-10 plays a key role in the modulation of neutrophils recruitment and lung inflammation during infection by Streptococcus pneumoniae

    PubMed Central

    Peñaloza, Hernán F; Nieto, Pamela A; Muñoz-Durango, Natalia; Salazar-Echegarai, Francisco J; Torres, Javiera; Parga, María J; Alvarez-Lobos, Manuel; Riedel, Claudia A; Kalergis, Alexis M; Bueno, Susan M

    2015-01-01

    Streptococcus pneumoniae is a major aetiological agent of pneumonia worldwide, as well as otitis media, sinusitis, meningitis and sepsis. Recent reports have suggested that inflammation of lungs due to S. pneumoniae infection promotes bacterial dissemination and severe disease. However, the contribution of anti-inflammatory molecules to the pathogenesis of S. pneumoniae remains unknown. To elucidate whether the production of the anti-inflammatory cytokine interleukin-10 (IL-10) is beneficial or detrimental for the host during pneumococcal pneumonia, we performed S. pneumoniae infections in mice lacking IL-10 (IL-10−/− mice). The IL-10−/− mice showed increased mortality, higher expression of pro-inflammatory cytokines, and an exacerbated recruitment of neutrophils into the lungs after S. pneumoniae infection. However, IL-10−/− mice showed significantly lower bacterial loads in lungs, spleen, brain and blood, when compared with mice that produced this cytokine. Our results support the notion that production of IL-10 during S. pneumoniae infection modulates the expression of pro-inflammatory cytokines and the infiltration of neutrophils into the lungs. This feature of IL-10 is important to avoid excessive inflammation of tissues and to improve host survival, even though bacterial dissemination is less efficient in the absence of this cytokine. PMID:26032199

  18. [Correlation analysis on combined medication with of Xiyanping injection in treatment of lung infection in real world].

    PubMed

    Yin, Xiu-ping; Xie, Yan-ming; Zhi, Ying-jie; Yang, Wei; Wang, Zhi-fei; Huo, Jian

    2015-06-01

    To analyze the regularity in combined medication with Xiyanping injection (Xiyanping for short) in the real world by as- sociation rules. Totally 5 822 patients using Xiyanping injection was collected from the 18 Class III Grade I hospitals nationwide to study the combined medication information of the patient with lung infection and make the analysis by using association rules and Apriori. According to the results, major drugs combined with Xiyanping in treatment of lung infection included compound amino acid, inosine, coenzyme A, cytidine triphosphate, vitamin C. Common drugs combined with Xiyanping can be divided into 5 categories: nutrition support therapy (vitamin C, compound amino acid) , coenzymes (coenzyme A, cytidine triphosphate, inosine), expectorants and antiasthmatics (ambroxol, salbutamol, doxofylline), hormones (dexamethasone, budesonide), antibiotics (mainly cefminox). The main combined medicines mostly conformed to the regularity for drugs treating lung infection. In addition, there were two most common medical combination models: the model for Xiyanping combined a single medicine is Xiyanping + nutrition support therapy, while the model for Xiyanping combined two or more than two medicines is Xiyanping + nutrition support therapy + coenzyme. Pharmacologically, Xiyanping is mostly combined with western medicines with similar pharmacological effects to substitute or supplement the antibiotic effect in treating lung infection. However, further studies shall be conducted for the safety and rationality of the combined medication based on clinical practices, in order to provide reference for clinical medication. PMID:26591539

  19. Inducible Expression of Inflammatory Chemokines in Respiratory Syncytial Virus-Infected Mice: Role of MIP-1α in Lung Pathology

    PubMed Central

    Haeberle, Helene A.; Kuziel, William A.; Dieterich, Hans-Juergen; Casola, Antonella; Gatalica, Zoran; Garofalo, Roberto P.

    2001-01-01

    Lower respiratory tract disease caused by respiratory syncytial virus (RSV) is characterized by profound airway mucosa inflammation, both in infants with naturally acquired infection and in experimentally inoculated animal models. Chemokines are central regulatory molecules in inflammatory, immune, and infectious processes of the lung. In this study, we demonstrate that intranasal infection of BALB/c mice with RSV A results in inducible expression of lung chemokines belonging to the CXC (MIP-2 and IP-10), CC (RANTES, eotaxin, MIP-1β, MIP-1α, MCP-1, TCA-3) and C (lymphotactin) families. Chemokine mRNA expression occurred as early as 24 h following inoculation and persisted for at least 5 days in mice inoculated with the highest dose of virus (107 PFU). In general, levels of chemokine mRNA and protein were dependent on the dose of RSV inoculum and paralleled the intensity of lung cellular inflammation. Immunohisthochemical studies indicated that RSV-induced expression of MIP-1α, one of the most abundantly expressed chemokines, was primarily localized in epithelial cells of the alveoli and bronchioles, as well as in adjoining capillary endothelium. Genetically altered mice with a selective deletion of the MIP-1α gene (−/− mice) demonstrated a significant reduction in lung inflammation following RSV infection, compared to control littermates (+/+ mice). Despite the paucity of infiltrating cells, the peak RSV titer in the lung of −/− mice was not significantly different from that observed in +/+ mice. These results provide the first direct evidence that RSV infection may induce lung inflammation via the early production of inflammatory chemokines. PMID:11134301

  20. Symbiosis in an overlooked microcosm: a systematic review of the bacterial flora of mites.

    PubMed

    Chaisiri, Kittipong; McGarry, John W; Morand, Serge; Makepeace, Benjamin L

    2015-08-01

    A dataset of bacterial diversity found in mites was compiled from 193 publications (from 1964 to January 2015). A total of 143 mite species belonging to the 3 orders (Mesostigmata, Sarcoptiformes and Trombidiformes) were recorded and found to be associated with approximately 150 bacteria species (in 85 genera, 51 families, 25 orders and 7 phyla). From the literature, the intracellular symbiont Cardinium, the scrub typhus agent Orientia, and Wolbachia (the most prevalent symbiont of arthropods) were the dominant mite-associated bacteria, with approximately 30 mite species infected each. Moreover, a number of bacteria of medical and veterinary importance were also reported from mites, including species from the genera Rickettsia, Anaplasma, Bartonella, Francisella, Coxiella, Borrelia, Salmonella, Erysipelothrix and Serratia. Significant differences in bacterial infection patterns among mite taxa were identified. These data will not only be useful for raising awareness of the potential for mites to transmit disease, but also enable a deeper understanding of the relationship of symbionts with their arthropod hosts, and may facilitate the development of intervention tools for disease vector control. This review provides a comprehensive overview of mite-associated bacteria and is a valuable reference database for future research on mites of agricultural, veterinary and/or medical importance.

  1. Expression of Toll-like receptor 4 in lungs of immune-suppressed rat with Acinetobacter baumannii infection

    PubMed Central

    Wang, Yanmei; Zhang, Xiaohong; Feng, Xuanlin; Liu, Xiaoshu; Deng, Lei; Liang, Zong-An

    2016-01-01

    Toll-like receptor 4 (TLR4) is involved in the regulation of host responses to Acinetobacter baumannii (A. baumannii). The aim of the present study was to examine the function of TLR4 in lung inflammation in immune-suppressed rats with A. baumannii infection. A total of 72 Sprague-Dawley male rats were randomly divided into the control, A. baumannii infection and immune-suppressed infection groups. The immune-suppressed infection group was treated with 100 mg/kg hydrocortisone by subcutaneous injection every other day for 2 weeks prior to A. baumannii infection. Lung tissue was obtained on the 3rd and 7th day after tracheal inoculation with A. baumannii. The expression of TLR4 in bronchial and alveolar epithelial cells, and alveolar macrophage was examined using immunohistochemistry. The levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α in bronchoalveolar lavage fluid were detected using ELISA. The results showed that in the control group, the expression of TLR4 was upregulated in the bronchial and alveolar epithelial, and alveolar macrophages, and the levels of IL-6 and TNF-α were increased in the early phase of A. baumannii infection. On the 7th day, no significant difference in the levels of IL-6 and TNF-α was observed between the A. baumannii infection and control groups. Conversely, the expression of TLR4 was downregulated in the immune-suppressed group, and the levels of IL-6 and TNF-α were reduced on the 3rd day after infection. In the subsequent observation period, the expression of TLR4 was upregulated and the levels of IL-6 and TNF-α were increased. In conclusion, the results show a critical role of TLR4 in mediating effective immune response in the lung of rat with A. baumannii infection. PMID:27703512

  2. Influenza A Virus Infection in Pigs Attracts Multifunctional and Cross-Reactive T Cells to the Lung

    PubMed Central

    Talker, Stephanie C.; Stadler, Maria; Koinig, Hanna C.; Mair, Kerstin H.; Rodríguez-Gómez, Irene M.; Graage, Robert; Zell, Roland; Dürrwald, Ralf; Starick, Elke; Harder, Timm; Weissenböck, Herbert; Lamp, Benjamin; Hammer, Sabine E.; Ladinig, Andrea; Saalmüller, Armin

    2016-01-01

    ABSTRACT Pigs are natural hosts for influenza A viruses and play a critical role in influenza epidemiology. However, little is known about their influenza-evoked T-cell response. We performed a thorough analysis of both the local and systemic T-cell response in influenza virus-infected pigs, addressing kinetics and phenotype as well as multifunctionality (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-2 [IL-2]) and cross-reactivity. A total of 31 pigs were intratracheally infected with an H1N2 swine influenza A virus (FLUAVsw) and consecutively euthanized. Lungs, tracheobronchial lymph nodes, and blood were sampled during the first 15 days postinfection (p.i.) and at 6 weeks p.i. Ex vivo flow cytometry of lung lymphocytes revealed an increase in proliferating (Ki-67+) CD8+ T cells with an early effector phenotype (perforin+ CD27+) at day 6 p.i. Low frequencies of influenza virus-specific IFN-γ-producing CD4+ and CD8+ T cells could be detected in the lung as early as 4 days p.i. On consecutive days, influenza virus-specific CD4+ and CD8+ T cells produced mainly IFN-γ and/or TNF-α, reaching peak frequencies around day 9 p.i., which were up to 30-fold higher in the lung than in tracheobronchial lymph nodes or blood. At 6 weeks p.i., CD4+ and CD8+ memory T cells had accumulated in lung tissue. These cells showed diverse cytokine profiles and in vitro reactivity against heterologous influenza virus strains, all of which supports their potential to combat heterologous influenza virus infections in pigs. IMPORTANCE Pigs not only are a suitable large-animal model for human influenza virus infection and vaccine development but also play a central role in the emergence of new pandemic strains. Although promising candidate universal vaccines are tested in pigs and local T cells are the major correlate of heterologous control, detailed and targeted analyses of T-cell responses at the site of infection are scarce. With the present study, we

  3. Choriodecidual Group B Streptococcal Inoculation Induces Fetal Lung Injury without Intra-Amniotic Infection and Preterm Labor in Macaca nemestrina

    PubMed Central

    Adams Waldorf, Kristina M.; Gravett, Michael G.; McAdams, Ryan M.; Paolella, Louis J.; Gough, G. Michael; Carl, David J.; Bansal, Aasthaa; Liggitt, H. Denny; Kapur, Raj P.; Reitz, Frederick B.; Rubens, Craig E.

    2011-01-01

    Background Early events leading to intrauterine infection and fetal lung injury remain poorly defined, but may hold the key to preventing neonatal and adult chronic lung disease. Our objective was to establish a nonhuman primate model of an early stage of chorioamnionitis in order to determine the time course and mechanisms of fetal lung injury in utero. Methodology/Principal Findings Ten chronically catheterized pregnant monkeys (Macaca nemestrina) at 118–125 days gestation (term = 172 days) received one of two treatments: 1) choriodecidual and intra-amniotic saline (n = 5), or 2) choriodecidual inoculation of Group B Streptococcus (GBS) 1×106 colony forming units (n = 5). Cesarean section was performed regardless of labor 4 days after GBS or 7 days after saline infusion to collect fetal and placental tissues. Only two GBS animals developed early labor with no cervical change in the remaining animals. Despite uterine quiescence in most cases, blinded review found histopathological evidence of fetal lung injury in four GBS animals characterized by intra-alveolar neutrophils and interstitial thickening, which was absent in controls. Significant elevations of cytokines in amniotic fluid (TNF-α, IL-8, IL-1β, IL-6) and fetal plasma (IL-8) were detected in GBS animals and correlated with lung injury (p<0.05). Lung injury was not directly caused by GBS, because GBS was undetectable in amniotic fluid (∼10 samples tested/animal), maternal and fetal blood by culture and polymerase chain reaction. In only two cases was GBS cultured from the inoculation site in low numbers. Chorioamnionitis occurred in two GBS animals with lung injury, but two others with lung injury had normal placental histology. Conclusions/Significance A transient choriodecidual infection can induce cytokine production, which is associated with fetal lung injury without overt infection of amniotic fluid, chorioamnionitis or preterm labor. Fetal lung injury may, thus, occur silently

  4. New Wolbachia supergroups detected in quill mites (Acari: Syringophilidae).

    PubMed

    Glowska, Eliza; Dragun-Damian, Anna; Dabert, Miroslawa; Gerth, Michael

    2015-03-01

    Wolbachia is the most abundant intracellular bacterial genus infecting a wide range of arthropods and filarial nematodes. Wolbachia have evolved parasitic, mutualistic and commensal relationships with their hosts but in arthropods generally act as reproductive parasites, inducing a wide range of phenotypic effects such as cytoplasmic incompatibility, parthenogenesis, feminization and male-killing. Up to now, the genus has been divided into 14 supergroups successively named A-O. Here, we describe two new Wolbachia supergroups from syringophilid mites (Acari: Cheyletoidea). These obligatory ectoparasites of birds inhabit the quills of feathers in many avian groups. The species of this family reproduce in a haplodiploid mode sensu arrhenotoky and are usually strongly female-biased. Based on the sequences of four protein-coding genes (ftsZ, gltA and groEL and coxA) and the 16S rRNA we identified strains of three Wolbachia supergroups (F and two distinct, yet undescribed ones) in five quill mite species. Our results suggest that in some cases the distribution of the bacteria can be better correlated with the mite's bird host rather than with mite taxonomy as such. The discovery of two new Wolbachia supergroups not only broadens the knowledge of the diversity of this bacterium but also raises questions about potential effects induced in quill mites and transmission mechanisms of the endosymbionts in this peculiar bacteria-quill mite-bird system.

  5. Lung epithelium and myeloid cells cooperate to clear acute pneumococcal infection

    PubMed Central

    Dudek, M; Puttur, F; Arnold-Schrauf, C; Kühl, A A; Holzmann, B; Henriques-Normark, B; Berod, L; Sparwasser, T

    2016-01-01

    The Gram-positive bacterium Streptococcus pneumoniae causes life-threatening infections, especially among immunocompromised patients. The host's immune system senses S. pneumoniae via different families of pattern recognition receptors, in particular the Toll-like receptor (TLR) family that promotes immune cell activation. Yet, while single TLRs are dispensable for initiating inflammatory responses against S. pneumoniae, the central TLR adapter protein myeloid differentiation factor 88 (MyD88) is of vital importance, as MyD88-deficient mice succumb rapidly to infection. Since MyD88 is ubiquitously expressed in hematopoietic and non-hematopoietic cells, the extent to which MyD88 signaling is required in different cell types to control S. pneumoniae is unknown. Therefore, we used novel conditional knockin mice to investigate the necessity of MyD88 signaling in distinct lung-resident myeloid and epithelial cells for the initiation of a protective immune response against S. pneumoniae. Here, we show that MyD88 signaling in lysozyme M (LysM)– and CD11c-expressing myeloid cells, as well as in pulmonary epithelial cells, is critical to restore inflammatory cytokine and antimicrobial peptide production, leading to efficient neutrophil recruitment and enhanced bacterial clearance. Overall, we show a novel synergistic requirement of compartment-specific MyD88 signaling in S. pneumoniae immunity. PMID:26627460

  6. Pseudomonas infection and mucociliary and absorptive clearance in the cystic fibrosis lung.

    PubMed

    Locke, Landon W; Myerburg, Michael M; Weiner, Daniel J; Markovetz, Matthew R; Parker, Robert S; Muthukrishnan, Ashok; Weber, Lawrence; Czachowski, Michael R; Lacy, Ryan T; Pilewski, Joseph M; Corcoran, Timothy E

    2016-05-01

    Airway surface liquid hyperabsorption and mucus accumulation are key elements of cystic fibrosis lung disease that can be assessed in vivo using functional imaging methods. In this study we evaluated experimental factors affecting measurements of mucociliary clearance (MCC) and small-molecule absorption (ABS) and patient factors associated with abnormal absorption and mucus clearance.Our imaging technique utilises two radiopharmaceutical probes delivered by inhalation. Measurement repeatability was assessed in 10 adult cystic fibrosis subjects. Experimental factors were assessed in 29 adult and paediatric cystic fibrosis subjects (51 scans). Patient factors were assessed in a subgroup with optimal aerosol deposition (37 scans; 24 subjects). Paediatric subjects (n=9) underwent initial and 2-year follow-up scans. Control subjects from a previously reported study are included for comparison.High rates of central aerosol deposition influenced measurements of ABS and, to a lesser extent, MCC. Depressed MCC in cystic fibrosis was only detectable in subjects with previous Pseudomonas aeruginosa infection. Cystic fibrosis subjects without P. aeruginosa had similar MCC to control subjects. Cystic fibrosis subjects had consistently higher ABS rates.We conclude that the primary experimental factor affecting MCC/ABS measurements is central deposition percentage. Depressed MCC in cystic fibrosis is associated with P. aeruginosa infection. ABS is consistently increased in cystic fibrosis.

  7. Lung epithelium and myeloid cells cooperate to clear acute pneumococcal infection.

    PubMed

    Dudek, M; Puttur, F; Arnold-Schrauf, C; Kühl, A A; Holzmann, B; Henriques-Normark, B; Berod, L; Sparwasser, T

    2016-09-01

    The Gram-positive bacterium Streptococcus pneumoniae causes life-threatening infections, especially among immunocompromised patients. The host's immune system senses S. pneumoniae via different families of pattern recognition receptors, in particular the Toll-like receptor (TLR) family that promotes immune cell activation. Yet, while single TLRs are dispensable for initiating inflammatory responses against S. pneumoniae, the central TLR adapter protein myeloid differentiation factor 88 (MyD88) is of vital importance, as MyD88-deficient mice succumb rapidly to infection. Since MyD88 is ubiquitously expressed in hematopoietic and non-hematopoietic cells, the extent to which MyD88 signaling is required in different cell types to control S. pneumoniae is unknown. Therefore, we used novel conditional knockin mice to investigate the necessity of MyD88 signaling in distinct lung-resident myeloid and epithelial cells for the initiation of a protective immune response against S. pneumoniae. Here, we show that MyD88 signaling in lysozyme M (LysM)- and CD11c-expressing myeloid cells, as well as in pulmonary epithelial cells, is critical to restore inflammatory cytokine and antimicrobial peptide production, leading to efficient neutrophil recruitment and enhanced bacterial clearance. Overall, we show a novel synergistic requirement of compartment-specific MyD88 signaling in S. pneumoniae immunity. PMID:26627460

  8. Baicalin from Scutellaria baicalensis blocks respiratory syncytial virus (RSV) infection and reduces inflammatory cell infiltration and lung injury in mice

    PubMed Central

    Shi, Hengfei; Ren, Ke; Lv, Baojie; Zhang, Wei; Zhao, Ying; Tan, Ren Xiang; Li, Erguang

    2016-01-01

    The roots of Scutellaria baicalensis has been used as a remedy for inflammatory and infective diseases for thousands of years. We evaluated the antiviral activity against respiratory syncytial virus (RSV) infection, the leading cause of childhood infection and hospitalization. By fractionation and chromatographic analysis, we determined that baicalin was responsible for the antiviral activity of S. baicalensis against RSV infection. The concentration for 50% inhibition (IC50) of RSV infection was determined at 19.9 ± 1.8 μM, while the 50% cytotoxic concentration (CC50) was measured at 370 ± 10 μM. We then used a mouse model of RSV infection to further demonstrate baicalin antiviral effect. RSV infection caused significant lung injury and proinflammatory response, including CD4 and CD8 T lymphocyte infiltration. Baicalin treatment resulted in reduction of T lymphocyte infiltration and gene expression of proinflammatory factors, while the treatment moderately reduced RSV titers recovered from the lung tissues. T lymphocyte infiltration and cytotoxic T lymphocyte modulated tissue damage has been identified critical factors of RSV disease. The study therefore demonstrates that baicalin subjugates RSV disease through antiviral and anti-inflammatory effect. PMID:27767097

  9. Oxidative stress in rat liver and lung induced by furanoterpenoids isolated from Fusarium solani infected sweet potatoes.

    PubMed

    Rajendran, S; Parasakthy, K; Deepalakshmi, P D; Devaraj, S N

    1996-01-01

    A crude extract containing some toxic furanoterpenoids was isolated from F. solani infected sweet potatoes. Chronic administration of the crude extract to male albino rats at a dosage of 1 mg/kg body weight/day for 21 days brought about a sharp increase in the thiobarbituric acid reactive substances and a depression of glutathione levels in the lung and liver homogenates. The antioxidant defense system was affected as evident from a significant fall in the activities of the enzymes, superoxide dismutase, catalase, glutathione peroxidase, glucose-6-phosphate dehydrogenase and glutathione-S-transferase. Such an alteration could be the reason for the lung and liver damage caused by these toxic furanoterpenoids.

  10. Evolution and diversification of Pseudomonas aeruginosa in the paranasal sinuses of cystic fibrosis children have implications for chronic lung infection.

    PubMed

    Hansen, Susse Kirkelund; Rau, Martin Holm; Johansen, Helle Krogh; Ciofu, Oana; Jelsbak, Lars; Yang, Lei; Folkesson, Anders; Jarmer, Hanne Østergaard; Aanæs, Kasper; von Buchwald, Christian; Høiby, Niels; Molin, Søren

    2012-01-01

    The opportunistic pathogen Pseudomonas aeruginosa is a frequent colonizer of the airways of patients suffering from cystic fibrosis (CF). Depending on early treatment regimens, the colonization will, with high probability, develop into chronic infections sooner or later, and it is important to establish under which conditions the switch to chronic infection takes place. In association with a recently established sinus surgery treatment program for CF patients at the Copenhagen CF Center, colonization of the paranasal sinuses with P. aeruginosa has been investigated, paralleled by sampling of sputum from the same patients. On the basis of genotyping and phenotypic characterization including transcription profiling, the diversity of the P. aeruginosa populations in the sinuses and the lower airways was investigated and compared. The observations made from several children show that the paranasal sinuses constitute an important niche for the colonizing bacteria in many patients. The paranasal sinuses often harbor distinct bacterial subpopulations, and in the early colonization phases there seems to be a migration from the sinuses to the lower airways, suggesting that independent adaptation and evolution take place in the sinuses. Importantly, before the onset of chronic lung infection, lineages with mutations conferring a large fitness benefit in CF airways such as mucA and lasR as well as small colony variants and antibiotic-resistant clones are part of the sinus populations. Thus, the paranasal sinuses potentially constitute a protected niche of adapted clones of P. aeruginosa, which can intermittently seed the lungs and pave the way for subsequent chronic lung infections.

  11. Parasitic scabies mites and associated bacteria joining forces against host complement defence.

    PubMed

    Swe, P M; Reynolds, S L; Fischer, K

    2014-11-01

    Scabies is a ubiquitous and contagious skin disease caused by the parasitic mite Sarcoptes scabiei Epidemiological studies have identified scabies as a causative agent for secondary skin infections caused by Staphylococcus aureus and Streptococcus pyogenes. This is an important notion, as such bacterial infections can lead to serious downstream life-threatening complications. As the complement system is the first line of host defence that confronts invading pathogens, both the mite and bacteria produce a large array of molecules that inhibit the complement cascades. It is hypothesised that scabies mite complement inhibitors may play an important role in providing a favourable micro-environment for the establishment of secondary bacterial infections. This review aims to bring together the current literature on complement inhibition by scabies mites and bacteria associated with scabies and to discuss the proposed molecular link between scabies and bacterial co-infections. PMID:25081184

  12. Efficacy of species-specific protein antibiotics in a murine model of acute Pseudomonas aeruginosa lung infection

    PubMed Central

    McCaughey, Laura C.; Ritchie, Neil. D.; Douce, Gillian R.; Evans, Thomas J.; Walker, Daniel

    2016-01-01

    Protein antibiotics, known as bacteriocins, are widely produced by bacteria for intraspecies competition. The potency and targeted action of bacteriocins suggests that they could be developed into clinically useful antibiotics against highly drug resistant Gram-negative pathogens for which there are few therapeutic options. Here we show that Pseudomonas aeruginosa specific bacteriocins, known as pyocins, show strong efficacy in a murine model of P. aeruginosa lung infection, with the concentration of pyocin S5 required to afford protection from a lethal infection at least 100-fold lower than the most commonly used inhaled antibiotic tobramycin. Additionally, pyocins are stable in the lung, poorly immunogenic at high concentrations and efficacy is maintained in the presence of pyocin specific antibodies after repeated pyocin administration. Bacteriocin encoding genes are frequently found in microbial genomes and could therefore offer a ready supply of highly targeted and potent antibiotics active against problematic Gram-negative pathogens. PMID:27444885

  13. Detection of C-type virus by immunoferritin technique in bat lung cell line chronically infected with bovine leucosis virus.

    PubMed

    Mihailescu, D; Patrascu, I V; Apostol, I; Mazilu, M

    1980-01-01

    Reported in this paper are morphological studies and tests for the detection of Type-C particles from a line of bat lung cells chronically infected with bovine leucosis virus. The immunoferritin technique was used. Ferritin labelling of Type-C particles was regularly accompanied by black-spot arrangement of ferritin around the virus envelope, which provided evidence to the specificity of this immunochemical technique. PMID:6260052

  14. An optimized two-photon method for in vivo lung imaging reveals intimate cell collaborations during infection

    NASA Astrophysics Data System (ADS)

    Fiole, Daniel; Deman, Pierre; Trescos, Yannick; Douady, Julien; Tournier, Jean-Nicolas

    2013-02-01

    Lung tissue motion arising from breathing and heart beating has been described as the largest annoyance of in vivo imaging. Consequently, infected lung tissue has never been imaged in vivo thus far, and little is known concerning the kinetics of the mucosal immune system at the cellular level. We have developed an optimized post-processing strategy to overcome tissue motion, based upon two-photon and second harmonic generation (SHG) microscopy. In contrast to previously published data, we have freed the lung parenchyma from any strain and depression in order to maintain the lungs under optimal physiological parameters. Excitation beams swept the sample throughout normal breathing and heart movements, allowing the collection of many images. Given that tissue motion is unpredictably, it was essential to sort images of interest. This step was enhanced by using SHG signal from collagen as a reference for sampling and realignment phases. A normalized cross-correlation criterion was used between a manually chosen reference image and rigid transformations of all others. Using CX3CR1+/gfp mice this process allowed the collection of high resolution images of pulmonary dendritic cells (DCs) interacting with Bacillus anthracis spores, a Gram-positive bacteria responsible for anthrax disease. We imaged lung tissue for up to one hour, without interrupting normal lung physiology. Interestingly, our data revealed unexpected interactions between DCs and macrophages, two specialized phagocytes. These contacts may participate in a better coordinate immune response. Our results not only demonstrate the phagocytizing task of lung DCs but also infer a cooperative role of alveolar macrophages and DCs.

  15. Lung Infection by Human Bocavirus Induces the Release of Profibrotic Mediator Cytokines In Vivo and In Vitro

    PubMed Central

    Karagiannidis, Christian; Bayh, Inga; Brockmann, Michael; Pieper, Monika; Windisch, Wolfram; Schildgen, Oliver; Schildgen, Verena

    2016-01-01

    Human Bocavirus subtype 1 (HBoV1) is associated with respiratory diseases and may contribute to chronic lung diseases by persisting in the infected host. Here the question was addressed if HBoV infections could contribute to fibrogenesis processes as suggested by previously published clinical observations. Cytokine profiles induced by HBoV infection in CuFi-8 air-liquid interphase cell cultures and in bronchoalveolar lavage fluid (BALF) of 20 HBoV-positive and 12 HBoV-negative patients were analysed by semi-quantitative Western spot blot analyses. Although lots of cytokines were regulated independently of HBoV status, several cytokines associated with lung fibrosis and tumour development, e.g., EGF, VEGF, TARC (CCL17), TNF-α, TNF-β, TIMP-1, were clearly upregulated in the HBoV-positive cohort. These findings suggest that the development of lung fibrosis might be triggered by HBoV induced cytokine expression. PMID:26807786

  16. [The tropical rat mite Ornithonyssus bacoti attacks humans in Iceland.].

    PubMed

    Skírnisson, K

    2001-12-01

    In the summer of 2001 the obligate, intermittent tropical rat mite Ornithonyssus bacoti attacked humans in an Icelandic household where infected Mongolian gerbils (Meriones unguiculatus), bought in a local pet shop, had been kept for few months. After a rapid proliferation the mite started attacking the humans living in the house. A boy sharing room with the pets suffered from extensive dermatitis. Optimal conditions for O. bacoti are at 24-26 degrees C and a relative humidity of 47%. Similar conditions frequently occur indoors in Icelandic premises. Therefore, if O. bacoti has been noticed indoors, necessary measures should be undertaken to immediately eliminate the pest. PMID:17019023

  17. Longevity and Developmental Stability in the Dung Fly Sepsis cynipsea, as Affected by the Ectoparasitic Mite, Pediculoides mesembrinae

    PubMed Central

    Martin, Oliver Y.; Hosken, David J.

    2009-01-01

    Fluctuating asymmetry (FA) is a widely employed measure of developmental stability. It has been found to increase with many stressors including parasite infection. Associations between parasites and FA may exist for several reasons in addition to parasites being the direct cause of increased FA. Developmentally stable individuals may have superior immune systems, and be less susceptible to parasite infection, and/or may be less exposed to parasites than developmentally unstable ones. Mites negatively impact host fitness in a number of insects, and if FA is a reflection of general genetic quality, as has been proposed, associations between mite number and FA are predicted. Potential relationships were investigated between an ectoparasitic mite, Pediculoides mesembrinae (Canestrini) (Phthiraptera: Menoponidae) and FA in the common dung fly Sepsis cynipsea (L.) (Diptera: Sepsidae). While it was found that mite infested flies died much faster than flies without mites, indicating that mites indeed stress their hosts, counter to expectations, no associations between mites and FA were found in any analyses. Additionally, FA in mite-infected flies generally did not differ from previously published FA data from uninfected S. cynipsea. Nevertheless, parasitized males tended to be somewhat less asymmetrical than non-parasitized males, but based on our data, it does not appear that mite infestation is generally associated with developmental stability in S. cynipsea. PMID:20053121

  18. Profile of cytokines in the lungs of BALB/c mice after intra-nasal infection with Histoplasma capsulatum mycelial propagules.

    PubMed

    Sahaza, Jorge Humberto; Suárez-Alvarez, Roberto; Estrada-Bárcenas, Daniel Alfonso; Pérez-Torres, Armando; Taylor, Maria Lucia

    2015-08-01

    The host pulmonary response to the fungus Histoplasma capsulatum was evaluated, through the profile of cytokines detected by the MagPix magnetic beads platform in lung homogenates and by lung-granulomas formation, from mice intra-nasally infected with mycelial propagules (M-phase) of two virulent H. capsulatum strains, EH-46 and G-217B. Results highlight that mice lung inflammatory response depends on the H. capsulatum strain used, during the first step of the fungal infection. IL-1β and TNF-α increased their concentrations in mice infected with both strains. The highest levels of IL-6, IL-17, and IL-23 were found in EH-46-infected mice, whereas levels of IL-22 were variable at all post-infection times for both strains. Significant increases of IL-12, IFN-γ, IL-4, and IL-10 were associated to EH-46-infected mice. Histological lung findings from EH-46-infected mice revealed incipient and numerous well-developed granulomas, distributed in lung-lobes at the 14th and the 21st days after infection, according to cytokine profiles.

  19. Molecular Prevalence of Acarapis Mite Infestations in Honey Bees in Korea.

    PubMed

    Ahn, Ah-Jin; Ahn, Kyu-Sung; Noh, Jin-Hyeong; Kim, Young-Ha; Yoo, Mi-Sun; Kang, Seung-Won; Yu, Do-Hyeon; Shin, Sung Shik

    2015-06-01

    Acarapis mites, including Acarapis woodi, Acarapis externus, and Acarapis dorsalis, are parasites of bees which can cause severe damage to the bee industry by destroying colonies and decreasing honey production. All 3 species are prevalent throughout many countries including UK, USA, Iran, Turkey, China, and Japan. Based on previous reports of Acarapis mites occurring in northeast Asia, including China and Japan, we investigated a survey of Acarapis mite infestations in honey bees in Korean apiaries. A total of 99 colonies of Apis mellifera were sampled from 5 provinces. The head and thorax of 20 bees from each colony were removed for DNA extraction. PCR assays were performed with 3 primer sets, including T, A, and K primers. Results indicated that 42.4% (42/99) of samples were Acarapis-positive by PCR assay which were sequenced to identify species. Each sequence showed 92.6-99.3% homology with reference sequences. Based on the homology, the number of colonies infected with A. dorsalis was 32 which showed the highest infection rate among the 3 species, while the number of colonies infected with A. externus and A. woodi was 9 and 1, respectively. However, none of the Acarapis mites were morphologically detected. This result could be explained that all apiaries in the survey used acaricides against bee mites such as Varroa destructor and Tropilaelaps clareae which also affect against Acarapis mites. Based on this study, it is highly probable that Acarapis mites as well as Varroa and Tropilaelaps could be prevalent in Korean apiaries.

  20. Requirement of the Pseudomonas aeruginosa CbrA Sensor Kinase for Full Virulence in a Murine Acute Lung Infection Model

    PubMed Central

    Yeung, Amy T. Y.; Janot, Laure; Pena, Olga M.; Neidig, Anke; Kukavica-Ibrulj, Irena; Hilchie, Ashley; Levesque, Roger C.; Overhage, Joerg

    2014-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen that is a major cause of respiratory tract and other nosocomial infections. The sensor kinase CbrA is a central regulator of carbon and nitrogen metabolism and in vitro also regulates virulence-related processes in P. aeruginosa. Here, we investigated the role of CbrA in two murine models of infection. In both peritoneal infections in leukopenic mice and lung infection models, the cbrA mutant was less virulent since substantially larger numbers of cbrA mutant bacteria were required to cause the same level of infection as wild-type or complemented bacteria. In contrast, in the chronic rat lung model the cbrA mutant grew and persisted as well as the wild type, indicating that the decrease of in vivo virulence of the cbrA mutant did not result from growth deficiencies on particular carbon substrates observed in vitro. In addition, a mutant in the cognate response regulator CbrB showed no defect in virulence in the peritoneal infection model, ruling out the involvement of certain alterations of virulence properties in the cbrA mutant including defective swarming motility, increased biofilm formation, and cytotoxicity, since these alterations are controlled through CbrB. Further investigations indicated that the mutant was more susceptible to uptake by phagocytes in vitro, resulting in greater overall bacterial killing. Consistent with the virulence defect, it took a smaller number of Dictyostelium discoideum amoebae to kill the cbrA mutant than to kill the wild type. Transcriptional analysis of the cbrA mutant during D. discoideum infection led to the conclusion that CbrA played an important role in the iron metabolism, protection of P. aeruginosa against oxidative stress, and the regulation of certain virulence factors. PMID:24379284

  1. Requirement of the Pseudomonas aeruginosa CbrA sensor kinase for full virulence in a murine acute lung infection model.

    PubMed

    Yeung, Amy T Y; Janot, Laure; Pena, Olga M; Neidig, Anke; Kukavica-Ibrulj, Irena; Hilchie, Ashley; Levesque, Roger C; Overhage, Joerg; Hancock, Robert E W

    2014-03-01

    Pseudomonas aeruginosa is an opportunistic pathogen that is a major cause of respiratory tract and other nosocomial infections. The sensor kinase CbrA is a central regulator of carbon and nitrogen metabolism and in vitro also regulates virulence-related processes in P. aeruginosa. Here, we investigated the role of CbrA in two murine models of infection. In both peritoneal infections in leukopenic mice and lung infection models, the cbrA mutant was less virulent since substantially larger numbers of cbrA mutant bacteria were required to cause the same level of infection as wild-type or complemented bacteria. In contrast, in the chronic rat lung model the cbrA mutant grew and persisted as well as the wild type, indicating that the decrease of in vivo virulence of the cbrA mutant did not result from growth deficiencies on particular carbon substrates observed in vitro. In addition, a mutant in the cognate response regulator CbrB showed no defect in virulence in the peritoneal infection model, ruling out the involvement of certain alterations of virulence properties in the cbrA mutant including defective swarming motility, increased biofilm formation, and cytotoxicity, since these alterations are controlled through CbrB. Further investigations indicated that the mutant was more susceptible to uptake by phagocytes in vitro, resulting in greater overall bacterial killing. Consistent with the virulence defect, it took a smaller number of Dictyostelium discoideum amoebae to kill the cbrA mutant than to kill the wild type. Transcriptional analysis of the cbrA mutant during D. discoideum infection led to the conclusion that CbrA played an important role in the iron metabolism, protection of P. aeruginosa against oxidative stress, and the regulation of certain virulence factors.

  2. 10 years of prophylaxis with nebulized liposomal amphotericin B and the changing epidemiology of Aspergillus spp. infection in lung transplantation.

    PubMed

    Peghin, Maddalena; Monforte, Victor; Martin-Gomez, Maria-Teresa; Ruiz-Camps, Isabel; Berastegui, Cristina; Saez, Berta; Riera, Jordi; Ussetti, Piedad; Solé, Juan; Gavaldá, Joan; Roman, Antonio

    2016-01-01

    The aim of this study was to assess the outcome and tolerability of prophylactic nebulized liposomal amphotericin B (n-LAB) in lung transplant recipients (LTR) and the changing epidemiology of Aspergillus spp. infection and colonization. We performed an observational study including consecutive LTR recipients (2003-2013) undergoing n-LAB prophylaxis lifetime. A total of 412 patients were included (mean postoperative follow-up 2.56 years; IQR 1.01-4.65). Fifty-three (12.8%) patients developed 59 Aspergillus spp. infections, and 22 invasive aspergillosis (overall incidence 5.3%). Since 2009, person-time incidence rates of Aspergillus spp. colonization and infection decreased (2003-2008, 0.19; 2009-2014, 0.09; P = 0.0007), but species with reduced susceptibility or resistance to amphotericin significantly increased (2003-2008, 38.1% vs 2009-2014, 58.1%; P = 0.039). Chronic lung allograft dysfunction (CLAD) was associated with Aspergillus spp. colonization and infection (HR 24.4, 95% CI 14.28-41.97; P = 0.00). Only 2.9% of patients presented adverse effects, and 1.7% required discontinuation. Long-term administration of prophylaxis with n-LAB has proved to be tolerable and can be used for preventing Aspergillus spp. infection in LTR. Over the last years, the incidence of Aspergillus spp. colonization and infection has decreased, but species with reduced amphotericin susceptibility or resistance are emerging. CLAD is associated with Aspergillus spp. colonization and infection.

  3. Listeria ivanovii Infection in Mice: Restricted to the Liver and Lung with Limited Replication in the Spleen

    PubMed Central

    Zhou, Mengying; Jiang, Mingjuan; Ren, Chenyan; Liu, Sijing; Pu, Qikang; Goldfine, Howard; Shen, Hao; Wang, Chuan

    2016-01-01

    Listeria monocytogenes (LM) vectors have shown much promise in delivery of viral and tumor antigens for the development of vaccines. L. ivanovii (LI) is a closely related bacterium with a similar intracellular life cycle that may offer advantages over LM because it is not a human pathogen, but can infect other animal species. Recent studies show that recombinant LI expressing Mycobacterium tuberculosis antigens is effective in inducing protective immunity in mouse models, demonstrating the potential of LI as a live vaccine vector. However, a key barrier in the development of LI into a live vaccine vector is that its pathogenic and immunogenic characteristics have yet to be fully understood. Therefore, in this research, C57BL/6J mice were inoculated with LM or LI intravenously or intranasally, and bacterial loads, histopathologic changes, and cytokine production were determined at indicated days post inoculation. Results showed that after intravenous infection with LM or LI, bacteria were found proliferating in the liver, spleen, and lung. However, LI could only reach a heavy burden in the liver and its ability to multiply and to resist host immunity seemed limited in the spleen and lung. After intranasal inoculation with LI, bacteria were mainly localized in the lung and failed to infect liver or spleen, while LM could. In organs with heavy LI burden, lesions were isolated, localized and densely packed, compared to lesions caused by LM, which were invasive. In the liver of intravenously inoculated mice and lung of intranasally inoculate mice, LI was able to elicit comparable cytokine production with LM and cause less severe histopathologic damages, and thus could be considered as a vector for treating or preventing hepatic or pulmonary diseases. PMID:27375558

  4. Cheyletus eruditus (taurrus): an effective candidate for the biological control of the snake mite (Ophionyssus natricis).

    PubMed

    Schilliger, Lionel H; Morel, Damien; Bonwitt, Jesse H; Marquis, Olivier

    2013-09-01

    The most commonly encountered ectoparasite in captive snakes is the hematophagous snake mite (Ophionyssus natricis). Infected snakes often exhibit lethargy, dysecdysis, pruritus, crusting dermatitis (sometimes progressing to abscesses), and behavioral changes (increased bathing time, rubbing against objects). Anemia and septicemia are occasional complications. Eliminating snake mites from a collection is frustrating. Insecticidal and acaricidal compounds used in mammals can be used against O. natricis infestation in reptiles, but they all are potentially neurotoxic to reptiles. The use of a biological agent to control the snake mite was first developed by using the predatory mites Hypoaspis miles and Hypoaspis aculeifer. However, no data are available regarding the potential of these mites to control O. natricis. Furthermore, the survival and predatory behavior of H. aculeifer and H. miles decreases above 28 degrees C, which is the lower value of the optimal temperature zone range required for rearing snakes. The aim of this study is to identify the ability of the predatory mite Cheyletus eruditus to control O. natricis. In the first experiment, 125 O. natricis mites where placed in separate plastic tubes together with the same number of C. eruditus mites. After 48 hr, the survival rate of snake mites was 6% compared with 92% in the control group (n = 125, P < 0,001). In the second experiment, 11 infested (average of 13 O. natricis per snake) ball pythons, with an average of 13 O. natricis per individual, were placed in separate cages with 1,000 C. eruditus mites + vermiculite After 15 days, only an average of two mites per snake remained, compared with 48 per snake in the control group (t-test, P < 0,01).

  5. Chronic lung infection by Pseudomonas aeruginosa biofilm is cured by L-Methionine in combination with antibiotic therapy

    PubMed Central

    Gnanadhas, Divya Prakash; Elango, Monalisha; Datey, Akshay; Chakravortty, Dipshikha

    2015-01-01

    Bacterial biofilms are associated with 80–90% of infections. Within the biofilm, bacteria are refractile to antibiotics, requiring concentrations >1,000 times the minimum inhibitory concentration. Proteins, carbohydrates and DNA are the major components of biofilm matrix. Pseudomonas aeruginosa (PA) biofilms, which are majorly associated with chronic lung infection, contain extracellular DNA (eDNA) as a major component. Herein, we report for the first time that L-Methionine (L-Met) at 0.5 μM inhibits Pseudomonas aeruginosa (PA) biofilm formation and disassembles established PA biofilm by inducing DNase expression. Four DNase genes (sbcB, endA, eddB and recJ) were highly up-regulated upon L-Met treatment along with increased DNase activity in the culture supernatant. Since eDNA plays a major role in establishing and maintaining the PA biofilm, DNase activity is effective in disrupting the biofilm. Upon treatment with L-Met, the otherwise recalcitrant PA biofilm now shows susceptibility to ciprofloxacin. This was reflected in vivo, in the murine chronic PA lung infection model. Mice treated with L-Met responded better to antibiotic treatment, leading to enhanced survival as compared to mice treated with ciprofloxacin alone. These results clearly demonstrate that L-Met can be used along with antibiotic as an effective therapeutic against chronic PA biofilm infection. PMID:26521707

  6. Haemophilus influenzae LicB contributes to lung damage in an aged mice co-infection model.

    PubMed

    Bondy, Jessica; Osharovich, Sofya; Storm, Julie; Durning, Graham; McAuliffe, Timothy; Fan, Xin

    2016-01-01

    Phosphorylcholine (ChoP) decoration of lipopolysaccharides is an important virulence strategy adopted by Haemophilus influenzae to establish a niche on the mucosal surface and to promote adherence to the host cells. The incorporation of ChoP on the LPS surface involves the lic1 operon, which consists of the licA, licB, licC, and licD genes. Among which, licB is a choline transporter gene required for acquisition of choline from environmental sources. In this study, we investigated the pathogenesis of the licB gene in an aged mice infection model. Due to immediate clearance of H. influenzae upon infection in mice, we employed influenza A virus and H. influenzae co-infection model. Our data showed that in the co-infection model, the secondary bacterial infection with a very low H. influenzae concentration of 100 colony forming unit is lethal to the aged mice. Although we did not observe any differences in weight loss between parent and licB mutant strains during the course of infection, a significant reduction of lung tissue damage was observed in the licB mutant infected aged mice. These results suggest that the licB gene is a virulence factor during H. influenzae infection in the lung in aged mice, possibly due to the increased binding to the host cell receptor via ChoP expression on the bacterial surface. In addition, when aged mice and mature mice were compared in the challenge experiments, we did not observe any protective immunity in the co-infection model suggesting the detrimental effects of the secondary bacterial infection on the aged mice in contrast to obvious immune-protections observed in the mature mice. The results of our experiments also implied that the co-infection model with influenza A virus and H. influenzae may be employed as a model system to study H. influenzae pathogenesis in vivo in aged mice.

  7. Retrospective Analysis of Bacterial and Viral Co-Infections in Pneumocystis spp. Positive Lung Samples of Austrian Pigs with Pneumonia.

    PubMed

    Weissenbacher-Lang, Christiane; Kureljušić, Branislav; Nedorost, Nora; Matula, Bettina; Schießl, Wolfgang; Stixenberger, Daniela; Weissenböck, Herbert

    2016-01-01

    Aim of this study was the retrospective investigation of viral (porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV), torque teno sus virus type 1 and 2 (TTSuV1, TTSuV2)) and bacterial (Bordetella bronchiseptica (B. b.), Mycoplasma hyopneumoniae (M. h.), and Pasteurella multocida (P. m.)) co-infections in 110 Pneumocystis spp. positive lung samples of Austrian pigs with pneumonia. Fifty-one % were positive for PCV2, 7% for PRRSV, 22% for TTSuV1, 48% for TTSuV2, 6% for B. b., 29% for M. h., and 21% for P. m. In 38.2% only viral, in 3.6% only bacterial and in 40.0% both, viral and bacterial pathogens were detected. In 29.1% of the cases a co-infection with 1 pathogen, in 28.2% with 2, in 17.3% with 3, and in 7.3% with 4 different infectious agents were observed. The exposure to Pneumocystis significantly decreased the risk of a co-infection with PRRSV in weaning piglets; all other odds ratios were not significant. Four categories of results were compared: I = P. spp. + only viral co-infectants, II = P. spp. + both viral and bacterial co-infectants, III = P. spp. + only bacterial co-infectants, and IV = P. spp. single infection. The evaluation of all samples and the age class of the weaning piglets resulted in a predomination of the categories I and II. In contrast, the suckling piglets showed more samples of category I and IV. In the group of fattening pigs, category II predominated. Suckling piglets can be infected with P. spp. early in life. With increasing age this single infections can be complicated by co-infections with other respiratory diseases. PMID:27428002

  8. Retrospective Analysis of Bacterial and Viral Co-Infections in Pneumocystis spp. Positive Lung Samples of Austrian Pigs with Pneumonia

    PubMed Central

    Weissenbacher-Lang, Christiane; Kureljušić, Branislav; Nedorost, Nora; Matula, Bettina; Schießl, Wolfgang; Stixenberger, Daniela; Weissenböck, Herbert

    2016-01-01

    Aim of this study was the retrospective investigation of viral (porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV), torque teno sus virus type 1 and 2 (TTSuV1, TTSuV2)) and bacterial (Bordetella bronchiseptica (B. b.), Mycoplasma hyopneumoniae (M. h.), and Pasteurella multocida (P. m.)) co-infections in 110 Pneumocystis spp. positive lung samples of Austrian pigs with pneumonia. Fifty-one % were positive for PCV2, 7% for PRRSV, 22% for TTSuV1, 48% for TTSuV2, 6% for B. b., 29% for M. h., and 21% for P. m. In 38.2% only viral, in 3.6% only bacterial and in 40.0% both, viral and bacterial pathogens were detected. In 29.1% of the cases a co-infection with 1 pathogen, in 28.2% with 2, in 17.3% with 3, and in 7.3% with 4 different infectious agents were observed. The exposure to Pneumocystis significantly decreased the risk of a co-infection with PRRSV in weaning piglets; all other odds ratios were not significant. Four categories of results were compared: I = P. spp. + only viral co-infectants, II = P. spp. + both viral and bacterial co-infectants, III = P. spp. + only bacterial co-infectants, and IV = P. spp. single infection. The evaluation of all samples and the age class of the weaning piglets resulted in a predomination of the categories I and II. In contrast, the suckling piglets showed more samples of category I and IV. In the group of fattening pigs, category II predominated. Suckling piglets can be infected with P. spp. early in life. With increasing age this single infections can be complicated by co-infections with other respiratory diseases. PMID:27428002

  9. Development of inhalable hyaluronan/mannitol composite dry powders for flucytosine repositioning in local therapy of lung infections.

    PubMed

    Costabile, G; d'Angelo, I; d'Emmanuele di Villa Bianca, R; Mitidieri, E; Pompili, B; Del Porto, P; Leoni, L; Visca, P; Miro, A; Quaglia, F; Imperi, F; Sorrentino, R; Ungaro, F

    2016-09-28

    Flucytosine (5-fluorocytosine, 5-FC) is a fluorinated analogue of cytosine currently approved for the systemic treatment of fungal infections, which has recently demonstrated a very promising antivirulence activity against the bacterial pathogen Pseudomonas aeruginosa. In this work, we propose novel inhalable hyaluronic acid (HA)/mannitol composite dry powders for repositioning 5-FC in the local treatment of lung infections, including those affecting cystic fibrosis (CF) patients. Different dry powders were produced in one-step by spray-drying. Powder composition and process conditions were selected after in depth formulation studies aimed at selecting the 5-FC/HA/mannitol formulation with convenient aerosolization properties and drug release profile in simulated lung fluids. The optimized 5-FC/HA/mannitol powder for inhalation (HyaMan_FC#3) was effectively delivered from different breath-activated dry powder inhalers (DPI) already available to CF patients. Nevertheless, the aerodynamic assessment of fine particles suggested that the developed formulation well fit with a low-resistance DPI. HyaMan_FC#3 inhibited the growth of the fungus Candida albicans and the production of the virulence factor pyoverdine by P. aeruginosa at 5-FC concentrations that did not affect the viability of both wild type (16HBE14o-) and CF (CFBE41o-) human bronchial epithelial cells. Finally, pharmacokinetics of HyaMan_FC#3 inhalation powder and 5-FC solution after intratracheal administration in rats were compared. In vivo results clearly demonstrated that, when formulated as dry powder, 5-FC levels in both bronchoalveolar lavage fluid and lung tissue were significantly higher and sustained over time as compared to those obtained with the 5-FC solution. Of note, when the same 5-FC amount was administered intravenously, no significant drug amount was found in the lung at each time point from the injection. To realize a 5-FC lung concentration similar to that obtained by using HyaMan_FC#3

  10. Development of inhalable hyaluronan/mannitol composite dry powders for flucytosine repositioning in local therapy of lung infections.

    PubMed

    Costabile, G; d'Angelo, I; d'Emmanuele di Villa Bianca, R; Mitidieri, E; Pompili, B; Del Porto, P; Leoni, L; Visca, P; Miro, A; Quaglia, F; Imperi, F; Sorrentino, R; Ungaro, F

    2016-09-28

    Flucytosine (5-fluorocytosine, 5-FC) is a fluorinated analogue of cytosine currently approved for the systemic treatment of fungal infections, which has recently demonstrated a very promising antivirulence activity against the bacterial pathogen Pseudomonas aeruginosa. In this work, we propose novel inhalable hyaluronic acid (HA)/mannitol composite dry powders for repositioning 5-FC in the local treatment of lung infections, including those affecting cystic fibrosis (CF) patients. Different dry powders were produced in one-step by spray-drying. Powder composition and process conditions were selected after in depth formulation studies aimed at selecting the 5-FC/HA/mannitol formulation with convenient aerosolization properties and drug release profile in simulated lung fluids. The optimized 5-FC/HA/mannitol powder for inhalation (HyaMan_FC#3) was effectively delivered from different breath-activated dry powder inhalers (DPI) already available to CF patients. Nevertheless, the aerodynamic assessment of fine particles suggested that the developed formulation well fit with a low-resistance DPI. HyaMan_FC#3 inhibited the growth of the fungus Candida albicans and the production of the virulence factor pyoverdine by P. aeruginosa at 5-FC concentrations that did not affect the viability of both wild type (16HBE14o-) and CF (CFBE41o-) human bronchial epithelial cells. Finally, pharmacokinetics of HyaMan_FC#3 inhalation powder and 5-FC solution after intratracheal administration in rats were compared. In vivo results clearly demonstrated that, when formulated as dry powder, 5-FC levels in both bronchoalveolar lavage fluid and lung tissue were significantly higher and sustained over time as compared to those obtained with the 5-FC solution. Of note, when the same 5-FC amount was administered intravenously, no significant drug amount was found in the lung at each time point from the injection. To realize a 5-FC lung concentration similar to that obtained by using HyaMan_FC#3

  11. Parasitic mites of medical and veterinary importance--is there a common research agenda?

    PubMed

    Fischer, Katja; Walton, Shelley

    2014-10-15

    There are an estimated 0.5-1 million mite species on earth. Among the many mites that are known to affect humans and animals, only a subset are parasitic but these can cause significant disease. We aim here to provide an overview of the most recent work in this field in order to identify common biological features of these parasites and to inform common strategies for future research. There is a critical need for diagnostic tools to allow for better surveillance and for drugs tailored specifically to the respective parasites. Multi-'omics' approaches represent a logical and timely strategy to identify the appropriate mite molecules. Recent advances in sequencing technology enable us to generate de novo genome sequence data, even from limited DNA resources. Consequently, the field of mite genomics has recently emerged and will now rapidly expand, which is a particular advantage for parasitic mites that cannot be cultured in vitro. Investigations of the microbiota associated with mites will elucidate the link between parasites and pathogens, and define the role of the mite in transmission and pathogenesis. The databases generated will provide the crucial knowledge essential to design novel diagnostic tools, control measures, prophylaxes, drugs and immunotherapies against the mites and associated secondary infections.

  12. Unique Type I Interferon Responses Determine the Functional Fate of Migratory Lung Dendritic Cells during Influenza Virus Infection

    PubMed Central

    Moltedo, Bruno; Li, Wenjing; Yount, Jacob S.; Moran, Thomas M.

    2011-01-01

    Migratory lung dendritic cells (DCs) transport viral antigen from the lungs to the draining mediastinal lymph nodes (MLNs) during influenza virus infection to initiate the adaptive immune response. Two major migratory DC subsets, CD103+ DCs and CD11bhigh DCs participate in this function and it is not clear if these antigen presenting cell (APC) populations become directly infected and if so whether their activity is influenced by the infection. In these experiments we show that both subpopulations can become infected and migrate to the draining MLN but a difference in their response to type I interferon (I-IFN) signaling dictates the capacity of the virus to replicate. CD103+ DCs allow the virus to replicate to significantly higher levels than do the CD11bhigh DCs, and they release infectious virus in the MLNs and when cultured ex-vivo. Virus replication in CD11bhigh DCs is inhibited by I-IFNs, since ablation of the I-IFN receptor (IFNAR) signaling permits virus to replicate vigorously and productively in this subset. Interestingly, CD103+ DCs are less sensitive to I-IFNs upregulating interferon-induced genes to a lesser extent than CD11bhigh DCs. The attenuated IFNAR signaling by CD103+ DCs correlates with their described superior antigen presentation capacity for naïve CD8+ T cells when compared to CD11bhigh DCs. Indeed ablation of IFNAR signaling equalizes the competency of the antigen presenting function for the two subpopulations. Thus, antigen presentation by lung DCs is proportional to virus replication and this is tightly constrained by I-IFN. The “interferon-resistant” CD103+ DCs may have evolved to ensure the presentation of viral antigens to T cells in I-IFN rich environments. Conversely, this trait may be exploitable by viral pathogens as a mechanism for systemic dissemination. PMID:22072965

  13. FleA Expression in Aspergillus fumigatus Is Recognized by Fucosylated Structures on Mucins and Macrophages to Prevent Lung Infection.

    PubMed

    Kerr, Sheena C; Fischer, Gregory J; Sinha, Meenal; McCabe, Orla; Palmer, Jonathan M; Choera, Tsokyi; Lim, Fang Yun; Wimmerova, Michaela; Carrington, Stephen D; Yuan, Shaopeng; Lowell, Clifford A; Oscarson, Stefan; Keller, Nancy P; Fahy, John V

    2016-04-01

    The immune mechanisms that recognize inhaled Aspergillus fumigatus conidia to promote their elimination from the lungs are incompletely understood. FleA is a lectin expressed by Aspergillus fumigatus that has twelve binding sites for fucosylated structures that are abundant in the glycan coats of multiple plant and animal proteins. The role of FleA is unknown: it could bind fucose in decomposed plant matter to allow Aspergillus fumigatus to thrive in soil, or it may be a virulence factor that binds fucose in lung glycoproteins to cause Aspergillus fumigatus pneumonia. Our studies show that FleA protein and Aspergillus fumigatus conidia bind avidly to purified lung mucin glycoproteins in a fucose-dependent manner. In addition, FleA binds strongly to macrophage cell surface proteins, and macrophages bind and phagocytose fleA-deficient (∆fleA) conidia much less efficiently than wild type (WT) conidia. Furthermore, a potent fucopyranoside glycomimetic inhibitor of FleA inhibits binding and phagocytosis of WT conidia by macrophages, confirming the specific role of fucose binding in macrophage recognition of WT conidia. Finally, mice infected with ΔfleA conidia had more severe pneumonia and invasive aspergillosis than mice infected with WT conidia. These findings demonstrate that FleA is not a virulence factor for Aspergillus fumigatus. Instead, host recognition of FleA is a critical step in mechanisms of mucin binding, mucociliary clearance, and macrophage killing that prevent Aspergillus fumigatus pneumonia. PMID:27058347

  14. Cigarette Smoke-Induced Lung Disease Predisposes to More Severe Infection with Nontypeable Haemophilus influenzae: Protective Effects of Andrographolide.

    PubMed

    Tan, W S Daniel; Peh, Hong Yong; Liao, Wupeng; Pang, Chu Hui; Chan, Tze Khee; Lau, Suk Hiang; Chow, Vincent T; Wong, W S Fred

    2016-05-27

    Cigarette smoke (CS) is associated with many maladies, one of which is chronic obstructive pulmonary disease (COPD). As the disease progresses, patients are more prone to develop COPD exacerbation episodes by bacterial infection, particularly to nontypeable Haemophilus influenza (NTHi) infection. The present study aimed to develop a CS-exposed mouse model that increases inflammation induced by NTHi challenge and investigate the protective effects of andrographolide, a bioactive molecule with anti-inflammatory and antioxidant properties isolated from the plant Andrographis paniculata. Female BALB/c mice exposed to 2 weeks of CS followed by a single intratracheal instillation of NTHi developed increased macrophage and neutrophil pulmonary infiltration, augmented cytokine levels, and heightened oxidative damage. Andrographolide effectively reduced lung cellular infiltrates and decreased lung levels of TNF-α, IL-1β, CXCL1/KC, 8-OHdG, matrix metalloproteinase-8 (MMP-8), and MMP-9. The protective actions of andrographolide on CS-predisposed NTHi inflammation might be attributable to increased nuclear factor erythroid-2-related factor 2 (Nrf2) activation and decreased Kelch-like ECH-associated protein 1 (Keap1) repressor function, resulting in enhanced gene expression of antioxidant enzymes including heme oxygenase-1 (HO-1), glutathione reductase (GR), glutathione peroxidase-2 (GPx-2), glutamate-cysteine ligase modifier (GCLM), and NAD(P)H quinone oxidoreductase 1 (NQO1). Taken together, these findings strongly support a therapeutic potential for andrographolide in preventing lung inflammation caused by NTHi in cigarette smokers.

  15. FleA Expression in Aspergillus fumigatus Is Recognized by Fucosylated Structures on Mucins and Macrophages to Prevent Lung Infection

    PubMed Central

    Sinha, Meenal; McCabe, Orla; Palmer, Jonathan M.; Choera, Tsokyi; Yun Lim, Fang; Wimmerova, Michaela; Carrington, Stephen D.; Yuan, Shaopeng; Lowell, Clifford A.; Oscarson, Stefan; Keller, Nancy P.; Fahy, John V.

    2016-01-01

    The immune mechanisms that recognize inhaled Aspergillus fumigatus conidia to promote their elimination from the lungs are incompletely understood. FleA is a lectin expressed by Aspergillus fumigatus that has twelve binding sites for fucosylated structures that are abundant in the glycan coats of multiple plant and animal proteins. The role of FleA is unknown: it could bind fucose in decomposed plant matter to allow Aspergillus fumigatus to thrive in soil, or it may be a virulence factor that binds fucose in lung glycoproteins to cause Aspergillus fumigatus pneumonia. Our studies show that FleA protein and Aspergillus fumigatus conidia bind avidly to purified lung mucin glycoproteins in a fucose-dependent manner. In addition, FleA binds strongly to macrophage cell surface proteins, and macrophages bind and phagocytose fleA-deficient (∆fleA) conidia much less efficiently than wild type (WT) conidia. Furthermore, a potent fucopyranoside glycomimetic inhibitor of FleA inhibits binding and phagocytosis of WT conidia by macrophages, confirming the specific role of fucose binding in macrophage recognition of WT conidia. Finally, mice infected with ΔfleA conidia had more severe pneumonia and invasive aspergillosis than mice infected with WT conidia. These findings demonstrate that FleA is not a virulence factor for Aspergillus fumigatus. Instead, host recognition of FleA is a critical step in mechanisms of mucin binding, mucociliary clearance, and macrophage killing that prevent Aspergillus fumigatus pneumonia. PMID:27058347

  16. FleA Expression in Aspergillus fumigatus Is Recognized by Fucosylated Structures on Mucins and Macrophages to Prevent Lung Infection.

    PubMed

    Kerr, Sheena C; Fischer, Gregory J; Sinha, Meenal; McCabe, Orla; Palmer, Jonathan M; Choera, Tsokyi; Lim, Fang Yun; Wimmerova, Michaela; Carrington, Stephen D; Yuan, Shaopeng; Lowell, Clifford A; Oscarson, Stefan; Keller, Nancy P; Fahy, John V

    2016-04-01

    The immune mechanisms that recognize inhaled Aspergillus fumigatus conidia to promote their elimination from the lungs are incompletely understood. FleA is a lectin expressed by Aspergillus fumigatus that has twelve binding sites for fucosylated structures that are abundant in the glycan coats of multiple plant and animal proteins. The role of FleA is unknown: it could bind fucose in decomposed plant matter to allow Aspergillus fumigatus to thrive in soil, or it may be a virulence factor that binds fucose in lung glycoproteins to cause Aspergillus fumigatus pneumonia. Our studies show that FleA protein and Aspergillus fumigatus conidia bind avidly to purified lung mucin glycoproteins in a fucose-dependent manner. In addition, FleA binds strongly to macrophage cell surface proteins, and macrophages bind and phagocytose fleA-deficient (∆fleA) conidia much less efficiently than wild type (WT) conidia. Furthermore, a potent fucopyranoside glycomimetic inhibitor of FleA inhibits binding and phagocytosis of WT conidia by macrophages, confirming the specific role of fucose binding in macrophage recognition of WT conidia. Finally, mice infected with ΔfleA conidia had more severe pneumonia and invasive aspergillosis than mice infected with WT conidia. These findings demonstrate that FleA is not a virulence factor for Aspergillus fumigatus. Instead, host recognition of FleA is a critical step in mechanisms of mucin binding, mucociliary clearance, and macrophage killing that prevent Aspergillus fumigatus pneumonia.

  17. [House dust mites and their allergens].

    PubMed

    Bessot, J-C; Pauli, G

    2011-02-01

    The taxonomy, anatomy, life cycle and ecology of Pyroglyphidae mites and storage mites (Acaridae, Glycyphagidae, B. tropicalis) are described. Pyroglyphidae and storage mites have similar morphologies: they are octopods, with characteristic gnathosoma and sensory hairs. Salivary glands and the mid gut produce most of the allergens excreted, which are enzymatic proteins. Biological cycles and development are similar, although fecundity is superior in storage mites compared to the Pyroglyphides. Relative humidity is the main parameter, which regulates mite development, with a higher degree of temperature and humidity required for storage mites. Bedding is the ecological niche of Pyroglyphidae, which feed on human skin. Moulds and food products are the storage mite biotope from which they spread in the dwelling. Initially considered as rural mites, storage mites are also present in urban dwellings. B. tropicalis, in tropical regions is a true domestic mite. Because of this, it is justified to denominate Pyroglyphidae "house dust mites" and storage mites "domestic mites". In addition to the respiratory allergic symptoms, the storage mites can also cause occupational contact dermatoses.

  18. Stenotrophomonas maltophilia Virulence and Specific Variations in Trace Elements during Acute Lung Infection: Implications in Cystic Fibrosis

    PubMed Central

    Crocetta, Valentina; Consalvo, Ada; Zappacosta, Roberta; Di Ilio, Carmine; Di Bonaventura, Giovanni

    2014-01-01

    Metal ions are necessary for the proper functioning of the immune system, and, therefore, they might have a significant influence on the interaction between bacteria and host. Ionic dyshomeostasis has been recently observed also in cystic fibrosis (CF) patients, whose respiratory tract is frequently colonized by Stenotrophomonas maltophilia. For the first time, here we used an inductively mass spectrometry method to perform a spatial and temporal analysis of the pattern of changes in a broad range of major trace elements in response to pulmonary infection by S. maltophilia. To this, DBA/2 mouse lungs were comparatively infected by a CF strain and by an environmental one. Our results showed that pulmonary ionomic profile was significantly affected during infection. Infected mice showed increased lung levels of Mg, P, S, K, Zn, Se, and Rb. To the contrary, Mn, Fe, Co, and Cu levels resulted significantly decreased. Changes of element concentrations were correlated with pulmonary bacterial load and markers of inflammation, and occurred mostly on day 3 post-exposure, when severity of infection culminated. Interestingly, CF strain – significantly more virulent than the environmental one in our murine model - provoked a more significant impact in perturbing pulmonary metal homeostasis. Particularly, exposure to CF strain exclusively increased P and K levels, while decreased Fe and Mn ones. Overall, our data clearly indicate that S. maltophilia modulates pulmonary metal balance in a concerted and virulence-dependent manner highlighting the potential role of the element dyshomeostasis during the progression of S. maltophilia infection, probably exacerbating the harmful effects of the loss of CF transmembrane conductance regulator function. Further investigations are required to understand the biological significance of these alterations and to confirm they are specifically caused by S. maltophilia. PMID:24586389

  19. Infection Rate and Tissue Localization of Murine IL-12p40-Producing Monocyte-Derived CD103+ Lung Dendritic Cells during Pulmonary Tuberculosis

    PubMed Central

    Leepiyasakulchai, Chaniya; Taher, Chato; Chuquimia, Olga D.; Mazurek, Jolanta; Söderberg-Naucler, Cecilia; Fernández, Carmen; Sköld, Markus

    2013-01-01

    Non-hematopoietic cells, including lung epithelial cells, influence host immune responses. By co-culturing primary alveolar epithelial cells and monocytes from naïve donor mice, we show that alveolar epithelial cells support monocyte survival and differentiation in vitro, suggesting a role for non-hematopoietic cells in monocyte differentiation during the steady state in vivo. CD103+ dendritic cells (αE-DC) are present at mucosal surfaces. Using a murine primary monocyte adoptive transfer model, we demonstrate that αE-DC in the lungs and pulmonary lymph nodes are monocyte-derived during pulmonary tuberculosis. The tissue localization may influence the functional potential of αE-DC that accumulate in Mycobacterium tuberculosis-infected lungs. Here, we confirm the localization of αE-DC in uninfected mice beneath the bronchial epithelial cell layer and near the vascular wall, and show that αE-DC have a similar distribution in the lungs during pulmonary tuberculosis and are detected in the bronchoalveolar lavage fluid from infected mice. Lung DC can be targeted by M. tuberculosis in vivo and play a role in bacterial dissemination to the draining lymph node. In contrast to other DC subsets, only a fraction of lung αE-DC are infected with the bacterium. We also show that virulent M. tuberculosis does not significantly alter cell surface expression levels of MHC class II on infected cells in vivo and that αE-DC contain the highest frequency of IL-12p40+ cells among the myeloid cell subsets in infected lungs. Our results support a model in which inflammatory monocytes are recruited into the M. tuberculosis-infected lung tissue and, depending on which non-hematopoietic cells they interact with, differentiate along different paths to give rise to multiple monocyte-derived cells, including DC with a distinctive αE-DC phenotype. PMID:23861965

  20. New hosts for the mite Ornithonyssus bursa in Argentina.

    PubMed

    Santillán, M Á; Grande, J M; Liébana, M S; Martínez, P; Díaz, L A; Bragagnolo, L A; Solaro, C; Galmes, M A; Sarasola, J H

    2015-12-01

    The mite Ornithonyssus bursa (Berlese) (Mesostigmata: Macronyssidae) is considered a poultry pest causing important infestations in chickens and it is considered a potential vector of arbovirus. Despite being considered a common parasite in wild birds, there is scarce published information about its potential hosts and effects on them. Here we present new bird hosts for O. bursa, assess the presence of Alphavirus, Flavivirus and Bunyavirus in mites from three host species, and discuss its potential impact on wild bird populations. We found O. bursa infecting five raptor and six passerine wild bird species. For nine of these species, this is the first record of infection by O. bursa. Although all analysed mites were negative for the examined arboviruses, the small sample size of mites does not allow further conclusions at the present moment. Because of the general nature of this ectoparasite, its presence in migratory long dispersal and endangered bird species, and the seropositivity for arboviruses in some of the species studied here, we consider it critical to assess the role of O. bursa and other ectoparasites as vectors and reservoirs of pathogens and as potential deleterious agents in wild bird populations. PMID:26258483

  1. New hosts for the mite Ornithonyssus bursa in Argentina.

    PubMed

    Santillán, M Á; Grande, J M; Liébana, M S; Martínez, P; Díaz, L A; Bragagnolo, L A; Solaro, C; Galmes, M A; Sarasola, J H

    2015-12-01

    The mite Ornithonyssus bursa (Berlese) (Mesostigmata: Macronyssidae) is considered a poultry pest causing important infestations in chickens and it is considered a potential vector of arbovirus. Despite being considered a common parasite in wild birds, there is scarce published information about its potential hosts and effects on them. Here we present new bird hosts for O. bursa, assess the presence of Alphavirus, Flavivirus and Bunyavirus in mites from three host species, and discuss its potential impact on wild bird populations. We found O. bursa infecting five raptor and six passerine wild bird species. For nine of these species, this is the first record of infection by O. bursa. Although all analysed mites were negative for the examined arboviruses, the small sample size of mites does not allow further conclusions at the present moment. Because of the general nature of this ectoparasite, its presence in migratory long dispersal and endangered bird species, and the seropositivity for arboviruses in some of the species studied here, we consider it critical to assess the role of O. bursa and other ectoparasites as vectors and reservoirs of pathogens and as potential deleterious agents in wild bird populations.

  2. Population Pharmacokinetics of Colistin Methanesulfonate in Rats: Achieving Sustained Lung Concentrations of Colistin for Targeting Respiratory Infections

    PubMed Central

    W. S. Yapa, Shalini; Li, Jian; Porter, Christopher J. H.; Nation, Roger L.

    2013-01-01

    Colistin methanesulfonate (CMS), the inactive prodrug of colistin, is administered by inhalation for the management of respiratory infections. However, limited pharmacokinetic data are available for CMS and colistin following pulmonary delivery. This study investigates the pharmacokinetics of CMS and colistin following intravenous (i.v.) and intratracheal (i.t.) administration in rats and determines the targeting advantage after direct delivery into the lungs. In addition to plasma, bronchoalveolar lavage (BAL) fluid was collected to quantify drug concentrations in lung epithelial lining fluid (ELF). The resulting data were analyzed using a population modeling approach in S-ADAPT. A three-compartment model described the disposition of both compounds in plasma following i.v. administration. The estimated mean clearance from the central compartment was 0.122 liters/h for CMS and 0.0657 liters/h for colistin. Conversion of CMS to colistin from all three compartments was required to fit the plasma data. The fraction of the i.v. dose converted to colistin in the systemic circulation was 0.0255. Two BAL fluid compartments were required to reflect drug kinetics in the ELF after i.t. dosing. A slow conversion of CMS (mean conversion time [MCTCMS] = 3.48 h) in the lungs contributed to high and sustained concentrations of colistin in ELF. The fraction of the CMS dose converted to colistin in ELF (fm,ELF = 0.226) was higher than the corresponding fractional conversion in plasma after i.v. administration. In conclusion, pulmonary administration of CMS achieves high and sustained exposures of colistin in lungs for targeting respiratory infections. PMID:23917323

  3. Antagonism of miR-328 Increases the Antimicrobial Function of Macrophages and Neutrophils and Rapid Clearance of Non-typeable Haemophilus Influenzae (NTHi) from Infected Lung

    PubMed Central

    Tay, Hock L.; Kaiko, Gerard E.; Plank, Maximilian; Li, JingJing; Maltby, Steven; Essilfie, Ama-Tawiah; Jarnicki, Andrew; Yang, Ming; Mattes, Joerg; Hansbro, Philip M.; Foster, Paul S.

    2015-01-01

    Pathogenic bacterial infections of the lung are life threatening and underpin chronic lung diseases. Current treatments are often ineffective potentially due to increasing antibiotic resistance and impairment of innate immunity by disease processes and steroid therapy. Manipulation miRNA directly regulating anti-microbial machinery of the innate immune system may boost host defence responses. Here we demonstrate that miR-328 is a key element of the host response to pulmonary infection with non-typeable haemophilus influenzae and pharmacological inhibition in mouse and human macrophages augments phagocytosis, the production of reactive oxygen species, and microbicidal activity. Moreover, inhibition of miR-328 in respiratory models of infection, steroid-induced immunosuppression, and smoke-induced emphysema enhances bacterial clearance. Thus, miRNA pathways can be targeted in the lung to enhance host defence against a clinically relevant microbial infection and offer a potential new anti-microbial approach for the treatment of respiratory diseases. PMID:25894560

  4. A Distinct Lung-Interstitium-Resident Memory CD8(+) T Cell Subset Confers Enhanced Protection to Lower Respiratory Tract Infection.

    PubMed

    Gilchuk, Pavlo; Hill, Timothy M; Guy, Clifford; McMaster, Sean R; Boyd, Kelli L; Rabacal, Whitney A; Lu, Pengcheng; Shyr, Yu; Kohlmeier, Jacob E; Sebzda, Eric; Green, Douglas R; Joyce, Sebastian

    2016-08-16

    The nature and anatomic location of the protective memory CD8(+) T cell subset induced by intranasal vaccination remain poorly understood. We developed a vaccination model to assess the anatomic location of protective memory CD8(+) T cells and their role in lower airway infections. Memory CD8(+) T cells elicited by local intranasal, but not systemic, vaccination with an engineered non-replicative CD8(+) T cell-targeted antigen confer enhanced protection to a lethal respiratory viral challenge. This protection depends on a distinct CXCR3(LO) resident memory CD8(+) T (Trm) cell population that preferentially localizes to the pulmonary interstitium. Because they are positioned close to the mucosa, where infection occurs, interstitial Trm cells act before inflammation can recruit circulating memory CD8(+) T cells into the lung tissue. This results in a local protective immune response as early as 1 day post-infection. Hence, vaccine strategies that induce lung interstitial Trm cells may confer better protection against respiratory pathogens. PMID:27498869

  5. Acaricide treatment affects viral dynamics in Varroa destructor-infested honey bee colonies via both host physiology and mite control.

    PubMed

    Locke, Barbara; Forsgren, Eva; Fries, Ingemar; de Miranda, Joachim R

    2012-01-01

    Honey bee (Apis mellifera) colonies are declining, and a number of stressors have been identified that affect, alone or in combination, the health of honey bees. The ectoparasitic mite Varroa destructor, honey bee viruses that are often closely associated with the mite, and pesticides used to control the mite population form a complex system of stressors that may affect honey bee health in different ways. During an acaricide treatment using Apistan (plastic strips coated with tau-fluvalinate), we analyzed the infection dynamics of deformed wing virus (DWV), sacbrood virus (SBV), and black queen cell virus (BQCV) in adult bees, mite-infested pupae, their associated Varroa mites, and uninfested pupae, comparing these to similar samples from untreated control colonies. Titers of DWV increased initially with the onset of the acaricide application and then slightly decreased progressively coinciding with the removal of the Varroa mite infestation. This initial increase in DWV titers suggests a physiological effect of tau-fluvalinate on the host's susceptibility to viral infection. DWV titers in adult bees and uninfested pupae remained higher in treated colonies than in untreated colonies. The titers of SBV and BQCV did not show any direct relationship with mite infestation and showed a variety of possible effects of the acaricide treatment. The results indicate that other factors besides Varroa mite infestation may be important to the development and maintenance of damaging DWV titers in colonies. Possible biochemical explanations for the observed synergistic effects between tau-fluvalinate and virus infections are discussed.

  6. Acaricide Treatment Affects Viral Dynamics in Varroa destructor-Infested Honey Bee Colonies via both Host Physiology and Mite Control

    PubMed Central

    Forsgren, Eva; Fries, Ingemar; de Miranda, Joachim R.

    2012-01-01

    Honey bee (Apis mellifera) colonies are declining, and a number of stressors have been identified that affect, alone or in combination, the health of honey bees. The ectoparasitic mite Varroa destructor, honey bee viruses that are often closely associated with the mite, and pesticides used to control the mite population form a complex system of stressors that may affect honey bee health in different ways. During an acaricide treatment using Apistan (plastic strips coated with tau-fluvalinate), we analyzed the infection dynamics of deformed wing virus (DWV), sacbrood virus (SBV), and black queen cell virus (BQCV) in adult bees, mite-infested pupae, their associated Varroa mites, and uninfested pupae, comparing these to similar samples from untreated control colonies. Titers of DWV increased initially with the onset of the acaricide application and then slightly decreased progressively coinciding with the removal of the Varroa mite infestation. This initial increase in DWV titers suggests a physiological effect of tau-fluvalinate on the host's susceptibility to viral infection. DWV titers in adult bees and uninfested pupae remained higher in treated colonies than in untreated colonies. The titers of SBV and BQCV did not show any direct relationship with mite infestation and showed a variety of possible effects of the acaricide treatment. The results indicate that other factors besides Varroa mite infestation may be important to the development and maintenance of damaging DWV titers in colonies. Possible biochemical explanations for the observed synergistic effects between tau-fluvalinate and virus infections are discussed. PMID:22020517

  7. Phosphodiesterase 4 inhibition reduces innate immunity and improves isoniazid clearance of Mycobacterium tuberculosis in the lungs of infected mice.

    PubMed

    Koo, Mi-Sun; Manca, Claudia; Yang, Guibin; O'Brien, Paul; Sung, Nackmoon; Tsenova, Liana; Subbian, Selvakumar; Fallows, Dorothy; Muller, George; Ehrt, Sabine; Kaplan, Gilla

    2011-02-25

    Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is one of the leading infectious disease causes of morbidity and mortality worldwide. Though current antibiotic regimens can cure the disease, treatment requires at least six months of drug therapy. One reason for the long duration of therapy is that the currently available TB drugs were selected for their ability to kill replicating organisms and are less effective against subpopulations of non-replicating persistent bacilli. Evidence from in vitro models of Mtb growth and mouse infection studies suggests that host immunity may provide some of the environmental cues that drive Mtb towards non-replicating persistence. We hypothesized that selective modulation of the host immune response to modify the environmental pressure on the bacilli may result in better bacterial clearance during TB treatment. For this proof of principal study, we compared bacillary clearance from the lungs of Mtb-infected mice treated with the anti-TB drug isoniazid (INH) in the presence and absence of an immunomodulatory phosphodiesterase 4 inhibitor (PDE4i), CC-3052. The effects of CC-3052 on host global gene expression, induction of cytokines, and T cell activation in the lungs of infected mice were evaluated. We show that CC-3052 modulates the innate immune response without causing generalized immune suppression. Immune modulation combined with INH treatment improved bacillary clearance and resulted in smaller granulomas and less lung pathology, compared to treatment with INH alone. This novel strategy of combining anti-TB drugs with an immune modulating molecule, if applied appropriately to patients, may shorten the duration of TB treatment and improve clinical outcome.

  8. Natural Anti-Infective Pulmonary Proteins: In Vivo Cooperative Action of Surfactant Protein SP-A and the Lung Antimicrobial Peptide SP-BN.

    PubMed

    Coya, Juan Manuel; Akinbi, Henry T; Sáenz, Alejandra; Yang, Li; Weaver, Timothy E; Casals, Cristina

    2015-08-15

    The anionic antimicrobial peptide SP-B(N), derived from the N-terminal saposin-like domain of the surfactant protein (SP)-B proprotein, and SP-A are lung anti-infective proteins. SP-A-deficient mice are more susceptible than wild-type mice to lung infections, and bacterial killing is enhanced in transgenic mice overexpressing SP-B(N). Despite their potential anti-infective action, in vitro studies indicate that several microorganisms are resistant to SP-A and SP-B(N). In this study, we test the hypothesis that these proteins act synergistically or cooperatively to strengthen each other's microbicidal activity. The results indicate that the proteins acted synergistically in vitro against SP-A- and SP-B(N)-resistant capsulated Klebsiella pneumoniae (serotype K2) at neutral pH. SP-A and SP-B(N) were able to interact in solution (Kd = 0.4 μM), which enabled their binding to bacteria with which SP-A or SP-B(N) alone could not interact. In vivo, we found that treatment of K. pneumoniae-infected mice with SP-A and SP-B(N) conferred more protection against K. pneumoniae infection than each protein individually. SP-A/SP-B(N)-treated infected mice showed significant reduction of bacterial burden, enhanced neutrophil recruitment, and ameliorated lung histopathology with respect to untreated infected mice. In addition, the concentrations of inflammatory mediators in lung homogenates increased early in infection in contrast with the weak inflammatory response of untreated K. pneumoniae-infected mice. Finally, we found that therapeutic treatment with SP-A and SP-B(N) 6 or 24 h after bacterial challenge conferred significant protection against K. pneumoniae infection. These studies show novel anti-infective pathways that could drive development of new strategies against pulmonary infections.

  9. A Case of Lung Cancer Originating from Cavitary Mycobacterium xenopi Infection.

    PubMed

    Doshi, Viral K; Kulkarni, Shreedhar R; Kham, Nang M; Kapitan, Kent S

    2015-03-01

    Coexistence of Mycobacterium xenopi with lung cancer has been reported. However, lung cancer originating within a pre-existing cavity caused by M. xenopi has not. A 55-y-old woman with a history of smoking presented with complaints of chronic dry cough, night sweats, and weight loss for several months. Computed tomography (CT) scanning revealed a 3.5-cm irregular thick-walled cavity in the right lung apex. Cultures obtained from a CT-guided biopsy grew M. xenopi. The patient received standard treatment, and her clinical symptoms improved, and the radiographic lesion stabilized. However, 2 y later, a repeat chest x-ray showed the original right upper lobe cavity with an interval development of a mass adjoining the cavity. A CT-guided needle biopsy of the new mass demonstrated squamous cell carcinoma. Whenever there is a change in the radiological appearance of a cavity, a repeat biopsy should be performed to exclude lung cancer. PMID:25336532

  10. Mast cells expedite control of pulmonary murine cytomegalovirus infection by enhancing the recruitment of protective CD8 T cells to the lungs.

    PubMed

    Ebert, Stefan; Becker, Marc; Lemmermann, Niels A W; Büttner, Julia K; Michel, Anastasija; Taube, Christian; Podlech, Jürgen; Böhm, Verena; Freitag, Kirsten; Thomas, Doris; Holtappels, Rafaela; Reddehase, Matthias J; Stassen, Michael

    2014-04-01

    The lungs are a noted predilection site of acute, latent, and reactivated cytomegalovirus (CMV) infections. Interstitial pneumonia is the most dreaded manifestation of CMV disease in the immunocompromised host, whereas in the immunocompetent host lung-infiltrating CD8 T cells confine the infection in nodular inflammatory foci and prevent viral pathology. By using murine CMV infection as a model, we provide evidence for a critical role of mast cells (MC) in the recruitment of protective CD8 T cells to the lungs. Systemic infection triggered degranulation selectively in infected MC. The viral activation of MC was associated with a wave of CC chemokine ligand 5 (CCL5) in the serum of C57BL/6 mice that was MC-derived as verified by infection of MC-deficient Kit(W-sh/W-sh) "sash" mutants. In these mutants, CD8 T cells were recruited less efficiently to the lungs, correlating with enhanced viral replication and delayed virus clearance. A causative role for MC was verified by MC reconstitution of "sash" mice restoring both, efficient CD8 T-cell recruitment and infection control. These results reveal a novel crosstalk axis between innate and adaptive immune defense against CMV, and identify MC as a hitherto unconsidered player in the immune surveillance at a relevant site of CMV disease. PMID:24763809

  11. Environmental silica in badger lungs: a possible association with susceptibility to Mycobacterium bovis infection

    SciTech Connect

    Higgins, D.A.; Kung, I.T.; Or, R.S.

    1985-04-01

    Badger lungs contain dark granular foci (0.2 to 2.0 mm) comprising aggregates of enlarged macrophages containing birefringent crystalline particles. Particles were examined from the lungs of three badgers; many were silicates and a significant number were pure silica (SiO/sub 2/). The particles and the accompanying pathology resembled mixed dust fibrosis and silicosis in humans, diseases associated with increased susceptibility to tuberculosis.

  12. Fatal attraction: Male spider mites prefer females killed by the mite-pathogenic fungus Neozygites floridana.

    PubMed

    Trandem, Nina; Bhattarai, Upendra Raj; Westrum, Karin; Knudsen, Geir Kjølberg; Klingen, Ingeborg

    2015-06-01

    Exploring prospective mates can be risky. Males of the spider mite Tetranychus urticae approach and guard immobile (quiescent) female nymphs to increase their chances of fathering offspring, this being a first-male sperm priority species. We investigated the behaviour of male T. urticae towards females killed by the mite pathogenic fungus Neozygites floridana, letting them choose between a fungal killed and a healthy quiescent female. The dead female (called cadaver) was in one of three stages: (1) non-sporulating; (2) sporulating with primary conidia (non-infective); (3) surrounded/partly covered by secondary capilliconidia (infective). When the cadaver was in stage 1 or 2, males were significantly more often observed near the cadaver than near the healthy female. When the cadaver was in stage 3 (infective capilliconidia), males preferred the vicinity of healthy females. The frequency of two male behaviours, touching and guarding, was also recorded. Touching the cadaver tended to decrease as cadaver developed, whereas touching the healthy females increased. Guarding of non-sporulating cadavers and healthy females was equally common, while guarding of sporulating cadavers was only observed once (stage 2) or not at all (stage 3). To differentiate between the effect of fungal infection and sex, we also let males choose between a non-sporulating cadaver of each sex. Males then preferred to approach the female cadaver. Touching behaviour followed the same pattern, and guarding of male cadavers was not observed. Our results indicate that T. urticae males are more attracted to non-infective female cadavers than to healthy females, only detecting their mistake when very close. Moreover, males approach and explore cadavers surrounded by infective conidia. Whether the results of host manipulation by the pathogen or just sensory constraints in the host, this inability to detect unsuitable and indeed infective mates promotes transmission of the pathogen.

  13. CLIMATE CONDITIONS AFFECTING THE WITHIN-PLANT SPREAD OF BROAD MITES ON AZALEA.

    PubMed

    Mechant, E; Pauwels, E; Gobin, B

    2014-01-01

    The broad mite Polyphagotarsonemus latus (Banks) is considered a major pest in potted azalea, Flanders' flagship ornamental crop of Rhododendron simsii hybrids. In addition to severe economic damage, the broad mite is dreaded for its increasing resistance to acaricides. Due to restrictions in the use of broad spectrum acaricides, Belgian azalea growers are left with only three compounds, belonging to two mode of action groups and restricted in their number of applications, for broad mite control: abamectin, milbemectin and pyrethrin. Although P. latus can be controlled with predatory mites, the high cost of this system makes it (not yet) feasible for integration into standard azalea pest management systems. Hence, a maximum efficacy of treatments with available compounds is essential. Because abamectin, milbemectin and pyrethrin are contact acaricides with limited trans laminar flow, only broad mites located on shoot tips of azalea plants will be controlled after spraying. Consequently, the efficacy of chemical treatments is influenced by the location and spread of P. latus on the plant. Unfortunately, little is known on broad mites' within-plant spread or how it is affected by climatic conditions like temperature and relative humidity. Therefore, experiments were set up to verify whether climate conditions have an effect on the location and migration of broad mites on azalea. Broad mite infected azalea plants were placed in standard growth chambers under different temperature (T:2.5-25°C) and relative humidity (RH:55-80%) treatments. Within-plant spread was determined by counting mites on the shoot tips and inner leaves of azalea plants. Results indicate that temperature and relative humidity have no significant effect on the within-plant spread of P. latus. To formulate recommendations for optimal spray conditions to maximize the efficacy of broad mite control with acaricides, further experiments on the effect of light intensity and rain are scheduled.

  14. Bone marrow transplantation alters lung antigen-presenting cells to promote TH17 response and the development of pneumonitis and fibrosis following gammaherpesvirus infection.

    PubMed

    Zhou, X; Loomis-King, H; Gurczynski, S J; Wilke, C A; Konopka, K E; Ptaschinski, C; Coomes, S M; Iwakura, Y; van Dyk, L F; Lukacs, N W; Moore, B B

    2016-05-01

    Hematopoietic stem cell transplantation (HSCT) efficacy is limited by numerous pulmonary complications. We developed a model of syngeneic bone marrow transplantion (BMT) followed by infection with murine gamma herpesvirus-68 that results in pneumonitis and fibrosis and mimics human "noninfectious" HSCT complications. BMT mice experience increased early lytic replication, but establish viral latency by 21 days post infection. CD4 T cells in BMT mice are skewed toward interleukin (IL)-17A rather than interferon (IFN)-γ production. Transplantation of bone marrow from Il-17a(-/-) donors or treatment with anti-IL-17A neutralization antibodies at late stages attenuates pneumonitis and fibrosis in infected BMT mice, suggesting that hematopoietic-derived IL-17A is essential for development of pathology. IL-17A directly influences activation and extracellular matrix production by lung mesenchymal cells. Lung CD11c+ cells of BMT mice secrete more transforming growth factor beta-β1, and pro-TH17 mRNAs for IL-23 and IL-6, and less TH1-promoting cytokine mRNA for IFN-γ but slightly more IL-12 mRNA in response to viral infection. Adoptive transfer of non-BMT lung CD11c-enriched cells restores robust TH1 response and suppresses aberrant TH17 response in BMT mice to improve lung pathology. Our data suggest that "noninfectious" HSCT lung complications may reflect preceding viral infections and demonstrate that IL-17A neutralization may offer therapeutic advantage even after disease onset. PMID:26376362

  15. Ectoparasitic mite and fungus on Harmonia axyridis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ectoparasitic mites (Acarina: Podapolipidae) and ectoparasitic fungi (Laboulbeniales: Laboulbeniaceae) occur on ladybirds (Coleoptera: Coccinellidae) throughout the world (Riddick et al., 2009). This study documents the interaction of a coccinellid-specific mite Coccipolipus hippodamiae (McDaniel &...

  16. Dust mite-proof pillow cover (image)

    MedlinePlus

    ... the amount of dust mites encase mattresses, box springs, and pillows with mite-proof covers. Further methods consist of washing bedding once a week in hot water, and dusting with a wet cloth once a ...

  17. Differential water mite parasitism, phenoloxidase activity, and resistance to mites are unrelated across pairs of related damselfly species.

    PubMed

    Mlynarek, Julia J; Iserbyt, Arne; Nagel, Laura; Forbes, Mark R

    2015-01-01

    Related host species often demonstrate differences in prevalence and/or intensity of infection by particular parasite species, as well as different levels of resistance to those parasites. The mechanisms underlying this interspecific variation in parasitism and resistance expression are not well understood. Surprisingly, few researchers have assessed relations between actual levels of parasitism and resistance to parasites seen in nature across multiple host species. The main goal of this study was to determine whether interspecific variation in resistance against ectoparasitic larval water mites either was predictive of interspecific variation in parasitism for ten closely related species of damselflies (grouped into five "species pairs"), or was predicted by interspecific variation in a commonly used measure of innate immunity (total Phenoloxidase or potential PO activity). Two of five species pairs had interspecific differences in proportions of individuals resisting larval Arrenurus water mites, only one of five species pairs had species differences in prevalence of larval Arrenurus water mites, and another two of five species pairs showed species differences in mean PO activity. Within the two species pairs where species differed in proportion of individuals resisting mites the species with the higher proportion did not have correspondingly higher PO activity levels. Furthermore, the proportion of individuals resisting mites mirrored prevalence of parasitism in only one species pair. There was no interspecific variation in median intensity of mite infestation within any species pair. We conclude that a species' relative ability to resist particular parasites does not explain interspecific variation in parasitism within species pairs and that neither resistance nor parasitism is reflected by interspecific variation in total PO or potential PO activity.

  18. The interferon-induced gene Ifi27l2a is active in lung macrophages and lymphocytes after influenza A infection but deletion of Ifi27l2a in mice does not increase susceptibility to infection.

    PubMed

    Tantawy, Mohamed A; Hatesuer, Bastian; Wilk, Esther; Dengler, Leonie; Kasnitz, Nadine; Weiß, Siegfried; Schughart, Klaus

    2014-01-01

    Interferons represent one of the first and essential host defense mechanisms after infection, and the activation of the IFN-pathway results in the transcriptional activation of hundreds of interferon-stimulated genes. The alpha-inducible protein 27 like 2A (Ifi27l2a) gene (human synonym: ISG12) is strongly up-regulated in the lung after influenza A infection in mice and has been shown in gene expression studies to be highly correlated to other activated genes. Therefore, we investigated the role of Ifi27l2a for the host defense to influenza A infections in more detail. RT-PCR analyses in non-infected mice demonstrated that Ifi27l2a was expressed in several tissues, including the lung. Detailed analyses of reporter gene expression in lungs from Ifi27l2a-LacZ mice revealed that Ifi27l2a was expressed in macrophages and lymphocytes but not in alveolar cells or bronchiolar epithelium cells. The number of macrophages and lymphocyte strongly increased in the lung after infection, but no significant increase in expression levels of the LacZ reporter gene was found within individual immune cells. Also, no reporter gene expression was found in bronchiolar epithelial cells, alveolar cells or infiltrating neutrophils after infection. Thus, up-regulation of Ifi27l2a in infected lungs is mainly due to the infiltration of macrophages and lymphocytes. Most surprisingly, deletion of Ifi27l2a in mouse knock-out lines did not result in increased susceptibility to infections with H1N1 or H7N7 influenza A virus compared to wild type C57BL/6N mice, suggesting a less important role of the gene for the host response to influenza infections than for bacterial infections. PMID:25184786

  19. Immunolocalization of pulmonary intravascular macrophages, TLR4, TLR9 and IL-8 in normal and Pasteurella multocida-infected lungs of water buffalo (Bubalus bubalis).

    PubMed

    Sethi, R S; Brar, R S; Singh, O; Singh, B

    2011-01-01

    Water buffalo are of considerable economic significance in South East Asia, but these animals suffer from many bacterial respiratory diseases including haemorrhagic septicaemia caused by Pasteurella multocida. Bacterial respiratory diseases of animals cause lung inflammation that is characterized by the activation of Toll-like receptors (TLRs) expressed on macrophages, expression of chemokines and recruitment of neutrophils and monocytes. Pulmonary intravascular macrophages (PIMs) present in the alveolar septa play a critical role in lung inflammation, but there are no data on the immunolocalization of PIMs or the expression of TLRs and chemokines such as interleukin (IL)-8, in the lungs of water buffalo. The present study compares the occurrence of PIMs, TLR4, TLR9 and IL-8 in the lungs of normal water buffalo and those infected with P. multocida. Labelling of PIMs with the anti-human macrophage antibody (MCA874G) demonstrated an increase in this population in inflamed lungs. TLR4 and IL-8 were detected in the alveolar septa, airway epithelium and endothelium of large blood vessels of normal lungs. TLR9 expression was similar to that of TLR4, but TLR9 was not expressed by the endothelium of arteries and veins. While the expression of TLR9 and IL-8 was increased in the inflamed lungs compared with normal lungs, TLR4 labelling intensity remained unchanged or was reduced. The expression of these molecules potentially plays a role in the regulation of lung inflammation.

  20. Effect of Temperature on Cystic Fibrosis Lung Disease and Infections: A Replicated Cohort Study

    PubMed Central

    Collaco, Joseph M.; McGready, John; Green, Deanna M.; Naughton, Kathleen M.; Watson, Christopher P.; Shields, Timothy; Bell, Scott C.; Wainwright, Claire E.

    2011-01-01

    Background Progressive lung disease accounts for the majority of morbidity and mortality observed in cystic fibrosis (CF). Beyond secondhand smoke exposure and socio-economic status, the effect of specific environmental factors on CF lung function is largely unknown. Methods Multivariate regression was used to assess correlation between specific environmental factors, the presence of pulmonary pathogens, and variation in lung function using subjects enrolled in the U.S. CF Twin and Sibling Study (CFTSS: n = 1378). Significant associations were tested for replication in the U.S. CF Foundation Patient Registry (CFF: n = 16439), the Australian CF Data Registry (ACFDR: n = 1801), and prospectively ascertained subjects from Australia/New Zealand (ACFBAL: n = 167). Results In CFTSS subjects, the presence of Pseudomonas aeruginosa (OR = 1.06 per °F; p<0.001) was associated with warmer annual ambient temperatures. This finding was independently replicated in the CFF (1.02; p<0.001), ACFDR (1.05; p = 0.002), and ACFBAL (1.09; p = 0.003) subjects. Warmer temperatures (−0.34 points per °F; p = 0.005) and public insurance (−6.43 points; p<0.001) were associated with lower lung function in the CFTSS subjects. These findings were replicated in the CFF subjects (temperature: −0.31; p<0.001; insurance: −9.11; p<0.001) and similar in the ACFDR subjects (temperature: −0.23; p = 0.057). The association between temperature and lung function was minimally influenced by P. aeruginosa. Similarly, the association between temperature and P. aeruginosa was largely independent of lung function. Conclusions Ambient temperature is associated with prevalence of P. aeruginosa and lung function in four independent samples of CF patients from two continents. PMID:22125624

  1. Flat mites of the world - Edition 2

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Flat Mites of the World has an interactive key, fact sheets, descriptions, and images to aid in the identification of flat mites (Acari: Trombidiformes: Tetranychoidea: Tenuipalpidae) worldwide. The tool will help identify 36 genera of flat mites, including specific diagnostics for 13 species of...

  2. Tilmicosin does not inhibit interleukin-8 gene expression in the bovine lung experimentally infected with Mannheimia (Pasteurella) haemolytica.

    PubMed

    Goubau, S; Morck, D W; Buret, A

    2000-10-01

    The expression of the interleukin-8 (IL-8) gene was examined by in situ hybridization in lung tissues from calves experimentally infected with Mannheimia (Pasteurella) haemolytica and treated with tilmicosin. Interleukin-8 mRNA expression was detected in alveolar areas, particularly along interlobular septa, in the lumen, and in the epithelial cells of some bronchioles. In lesional lung tissues from animals that had received tilmicosin, we found large areas with limited inflammation. There was no staining for IL-8 mRNA in these areas. In contrast, in strongly inflamed areas, the same patterns and intensities of staining for IL-8 mRNA were detected in tilmicosin- and sham-treated animals. We conclude that tilmicosin does not affect the expression of IL-8 mRNA in tissue showing microscopic signs of inflammation. Together with previous reports, this supports the view that the pro-apoptotic properties of tilmicosin on neutrophils do not compromise the host defense mechanisms required to control the infection.

  3. Affect of Early Life Oxygen Exposure on Proper Lung Development and Response to Respiratory Viral Infections

    PubMed Central

    Domm, William; Misra, Ravi S.; O’Reilly, Michael A.

    2015-01-01

    Children born preterm often exhibit reduced lung function and increased severity of response to respiratory viruses, suggesting that premature birth has compromised proper development of the respiratory epithelium and innate immune defenses. Increasing evidence suggests that premature birth promotes aberrant lung development likely due to the neonatal oxygen transition occurring before pulmonary development has matured. Given that preterm infants are born at a point of time where their immune system is also still developing, early life oxygen exposure may also be disrupting proper development of innate immunity. Here, we review current literature in hopes of stimulating research that enhances understanding of how the oxygen environment at birth influences lung development and host defense. This knowledge may help identify those children at risk for disease and ideally culminate in the development of novel therapies that improve their health. PMID:26322310

  4. Flagellin induces myeloid-derived suppressor cells: implications for Pseudomonas aeruginosa infection in cystic fibrosis lung disease.

    PubMed

    Rieber, Nikolaus; Brand, Alina; Hector, Andreas; Graepler-Mainka, Ute; Ost, Michael; Schäfer, Iris; Wecker, Irene; Neri, Davide; Wirth, Andreas; Mays, Lauren; Zundel, Sabine; Fuchs, Jörg; Handgretinger, Rupert; Stern, Martin; Hogardt, Michael; Döring, Gerd; Riethmüller, Joachim; Kormann, Michael; Hartl, Dominik

    2013-02-01

    Pseudomonas aeruginosa persists in patients with cystic fibrosis (CF) and drives CF lung disease progression. P. aeruginosa potently activates the innate immune system, mainly mediated through pathogen-associated molecular patterns, such as flagellin. However, the host is unable to eradicate this flagellated bacterium efficiently. The underlying immunological mechanisms are incompletely understood. Myeloid-derived suppressor cells (MDSCs) are innate immune cells generated in cancer and proinflammatory microenvironments and are capable of suppressing T cell responses. We hypothesized that P. aeruginosa induces MDSCs to escape T cell immunity. In this article, we demonstrate that granulocytic MDSCs accumulate in CF patients chronically infected with P. aeruginosa and correlate with CF lung disease activity. Flagellated P. aeruginosa culture supernatants induced the generation of MDSCs, an effect that was 1) dose-dependently mimicked by purified flagellin protein, 2) significantly reduced using flagellin-deficient P. aeruginosa bacteria, and 3) corresponded to TLR5 expression on MDSCs in vitro and in vivo. Both purified flagellin and flagellated P. aeruginosa induced an MDSC phenotype distinct from that of the previously described MDSC-inducing cytokine GM-CSF, characterized by an upregulation of the chemokine receptor CXCR4 on the surface of MDSCs. Functionally, P. aeruginosa-infected CF patient ex vivo-isolated as well as flagellin or P. aeruginosa in vitro-generated MDSCs efficiently suppressed polyclonal T cell proliferation in a dose-dependent manner and modulated Th17 responses. These studies demonstrate that flagellin induces the generation of MDSCs and suggest that P. aeruginosa uses this mechanism to undermine T cell-mediated host defense in CF and other P. aeruginosa-associated chronic lung diseases. PMID:23277486

  5. Toward Repositioning Niclosamide for Antivirulence Therapy of Pseudomonas aeruginosa Lung Infections: Development of Inhalable Formulations through Nanosuspension Technology.

    PubMed

    Costabile, Gabriella; d'Angelo, Ivana; Rampioni, Giordano; Bondì, Roslen; Pompili, Barbara; Ascenzioni, Fiorentina; Mitidieri, Emma; d'Emmanuele di Villa Bianca, Roberta; Sorrentino, Raffaella; Miro, Agnese; Quaglia, Fabiana; Imperi, Francesco; Leoni, Livia; Ungaro, Francesca

    2015-08-01

    Inhaled antivirulence drugs are currently considered a promising therapeutic option to treat Pseudomonas aeruginosa lung infections in cystic fibrosis (CF). We have recently shown that the anthelmintic drug niclosamide (NCL) has strong quorum sensing (QS) inhibiting activity against P. aeruginosa and could be repurposed as an antivirulence drug. In this work, we developed dry powders containing NCL nanoparticles that can be reconstituted in saline solution to produce inhalable nanosuspensions. NCL nanoparticles were produced by high-pressure homogenization (HPH) using polysorbate 20 or polysorbate 80 as stabilizers. After 20 cycles of HPH, all formulations showed similar properties in the form of needle-shape nanocrystals with a hydrodynamic diameter of approximately 450 nm and a zeta potential of -20 mV. Nanosuspensions stabilized with polysorbate 80 at 10% w/w to NCL (T80_10) showed an optimal solubility profile in simulated interstitial lung fluid. T80_10 was successfully dried into mannitol-based dry powder by spray drying. Dry powder (T80_10 DP) was reconstituted in saline solution and showed optimal in vitro aerosol performance. Both T80_10 and T80_10 DP were able to inhibit P. aeruginosa QS at NCL concentrations of 2.5-10 μM. NCL, and these formulations did not significantly affect the viability of CF bronchial epithelial cells in vitro at microbiologically active concentrations (i.e., ≤10 μM). In vivo acute toxicity studies in rats confirmed no observable toxicity of the NCL T80_10 DP formulation upon intratracheal administration at a concentration 100-fold higher than the anti-QS activity concentration. These preliminary results suggest that NCL repurposed in the form of inhalable nanosuspensions has great potential for the local treatment of P. aeruginosa lung infections as in the case of CF patients.

  6. Dermanyssus gallinae (chicken mite): an underdiagnosed environmental infestation.

    PubMed

    Collgros, H; Iglesias-Sancho, M; Aldunce, M J; Expósito-Serrano, V; Fischer, C; Lamas, N; Umbert-Millet, P

    2013-06-01

    Dermanyssus gallinae is a mite that normally parasitizes small birds but may occasionally bite humans. We report an unusual case of an 82-year-old woman who presented with pruritus and bite-like lesions over her trunk. Other members of the household were also affected. On physical examination, mites < 1 mm in size were found on the patient's body. The family were residing in the city centre and had no pets, but there were pigeon nests in close proximity to the house. Most dermatologists have difficulties identifying ectoparasitosis. In the case of D. gallinae, the small size of the mites and the fact that they leave the host after feeding means that they may not be seen at presentation, thus such infestations are likely to be underdiagnosed. Physicians should be aware that infection with this mite is possible even in patients from urban areas, and it should be included in the differential diagnosis of conditions causing recurrent pruritus unresponsive to standard treatments.

  7. Systems Medicine for Lung Diseases: Phenotypes and Precision Medicine in Cancer, Infection, and Allergy.

    PubMed

    Schmeck, Bernd; Bertrams, Wilhelm; Lai, Xin; Vera, Julio

    2016-01-01

    Lung diseases cause an enormous socioeconomic burden. Four of them are among the ten most important causes of deaths worldwide: Pneumonia has the highest death toll of all infectious diseases, lung cancer kills the most people of all malignant proliferative disorders, chronic obstructive pulmonary disease (COPD) ranks third in mortality among the chronic noncommunicable diseases, and tuberculosis is still one of the most important chronic infectious diseases. Despite all efforts, for example, by the World Health Organization and clinical and experimental researchers, these diseases are still highly prevalent and harmful. This is in part due to the specific organization of tissue homeostasis, architecture, and immunity of the lung. Recently, several consortia have formed and aim to bring together clinical and molecular data from big cohorts of patients with lung diseases with novel experimental setups, biostatistics, bioinformatics, and mathematical modeling. This "systems medicine" concept will help to match the different disease modalities with adequate therapeutic and possibly preventive strategies for individual patients in the sense of precision medicine.

  8. High Varroa mite abundance influences chemical profiles of worker bees and mite-host preferences.

    PubMed

    Cervo, R; Bruschini, C; Cappa, F; Meconcelli, S; Pieraccini, G; Pradella, D; Turillazzi, S

    2014-09-01

    Honeybee disappearance is one of the major environmental and economic challenges this century has to face. The ecto-parasitic mite Varroa destructor represents one of the main causes of the worldwide beehive losses. Although halting mite transmission among beehives is of primary importance to save honeybee colonies from further decline, the natural route used by mites to abandon a collapsing colony has not been extensively investigated so far. Here, we explored whether, with increasing mite abundance within the colony, mites change their behaviour to maximize the chances of leaving a highly infested colony. We show that, at low mite abundance, mites remain within the colony and promote their reproduction by riding nurses that they distinguish from foragers by different chemical cuticular signatures. When mite abundance increases, the chemical profile of nurses and foragers tends to overlap, promoting mite departure from exploited colonies by riding pollen foragers. PMID:25165133

  9. Why do Varroa mites prefer nurse bees?

    PubMed Central

    Xie, Xianbing; Huang, Zachary Y.; Zeng, Zhijiang

    2016-01-01

    The Varroa mite, Varroa destructor, is an acarine ecto-parasite on Apis mellifera. It is the worst pest of Apis mellifera, yet its reproductive biology on the host is not well understood. In particular, the significance of the phoretic stage, when mites feed on adult bees for a few days, is not clear. In addition, it is not clear whether the preference of mites for nurses observed in the laboratory also happens inside real colonies. We show that Varroa mites prefer nurses over both newly emerged bees and forgers in a colony setting. We then determined the mechanism behind this preference. We show that this preference maximizes Varroa fitness, although due to the fact that each mite must find a second host (a pupa) to reproduce, the fitness benefit to the mites is not immediate but delayed. Our results suggest that the Varroa mite is a highly adapted parasite for honey bees. PMID:27302644

  10. Honey Bees: Sweetness and Mites

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Honey bee colony losses have been in the news lately and the potential reasons for these losses have taken up much space in the news media. In order to clarify what role mites play in the current loss (2006-2007) of bee colonies, called Colony Collapse Disorder, a better understanding of what a mit...

  11. House dust mites, our intimate associates.

    PubMed

    Nadchatram, M

    2005-06-01

    House dust mites have lived in human contact from time immemorial. Human dander or dead skin constitutes the major organic component of the house dust ecosystem. Because the mites feed on dander, dust mites and human association will continue to co-exist as part of our environment. Efficient house-keeping practice is the best form of control to reduce infestation. However, special precautions are important when individuals are susceptible or sensitive to dust mites. House dust mites are responsible for causing asthma, rhinitis and contact dermatitis. The respiratory allergies are caused by the inhalation of dead or live mites, their faecal matter or other byproducts. Immune factors are of paramount importance in the development of dust related or mite induced respiratory diseases. House dust mites were found in some 1,000 samples of dust taken from approximately 330 dwellings in Peninsular Malaysia and Singapore. Mattresses, carpets, corners of a bedroom, and floor beneath the bed are favourable dust mite habitats. The incriminating species based on studies here and elsewhere, as well as many other species of dust mites of unknown etiological importance are widely distributed in Malaysian homes. Density of dust mites in Malaysia and Singapore is greater than in temperate countries. Prevention and control measures with reference to subjects sensitive to dust mite allergies, including chemical control described in studies conducted in Europe and America are discussed. However, a cost free and most practical way to remove mites, their faecal matter and other products is to resort to sunning the bedding and carpets to kill the living mites, and then beaten and brushed to remove the dust and other components.

  12. Influenza Virus Infects Epithelial Stem/Progenitor Cells of the Distal Lung: Impact on Fgfr2b-Driven Epithelial Repair

    PubMed Central

    Quantius, Jennifer; Schmoldt, Carole; Vazquez-Armendariz, Ana I.; Becker, Christin; El Agha, Elie; Wilhelm, Jochen; Morty, Rory E.; Vadász, István; Mayer, Konstantin; Gattenloehner, Stefan; Fink, Ludger; Matrosovich, Mikhail; Li, Xiaokun; Seeger, Werner; Lohmeyer, Juergen; Bellusci, Saverio; Herold, Susanne

    2016-01-01

    Influenza Virus (IV) pneumonia is associated with severe damage of the lung epithelium and respiratory failure. Apart from efficient host defense, structural repair of the injured epithelium is crucial for survival of severe pneumonia. The molecular mechanisms underlying stem/progenitor cell mediated regenerative responses are not well characterized. In particular, the impact of IV infection on lung stem cells and their regenerative responses remains elusive. Our study demonstrates that a highly pathogenic IV infects various cell populations in the murine lung, but displays a strong tropism to an epithelial cell subset with high proliferative capacity, defined by the signature EpCamhighCD24lowintegrin(α6)high. This cell fraction expressed the stem cell antigen-1, highly enriched lung stem/progenitor cells previously characterized by the signature integrin(β4)+CD200+, and upregulated the p63/krt5 regeneration program after IV-induced injury. Using 3-dimensional organoid cultures derived from these epithelial stem/progenitor cells (EpiSPC), and in vivo infection models including transgenic mice, we reveal that their expansion, barrier renewal and outcome after IV-induced injury critically depended on Fgfr2b signaling. Importantly, IV infected EpiSPC exhibited severely impaired renewal capacity due to IV-induced blockade of β-catenin-dependent Fgfr2b signaling, evidenced by loss of alveolar tissue repair capacity after intrapulmonary EpiSPC transplantation in vivo. Intratracheal application of exogenous Fgf10, however, resulted in increased engagement of non-infected EpiSPC for tissue regeneration, demonstrated by improved proliferative potential, restoration of alveolar barrier function and increased survival following IV pneumonia. Together, these data suggest that tropism of IV to distal lung stem cell niches represents an important factor of pathogenicity and highlight impaired Fgfr2b signaling as underlying mechanism. Furthermore, increase of alveolar Fgf10

  13. Eradication of elephant ear mites (Loxoanoetus bassoni) in two African elephants (Loxodonta africana).

    PubMed

    Wyatt, Jeff; DiVincenti, Louis

    2012-03-01

    Elephant ear mites, not previously described in North America, were eradicated in two African elephants (Loxodonta africana) after six otic instillations of ivermectin at 2-wk intervals. The microscopic examination of a clear, mucoid discharge collected from the external ear canals of two wild-born African elephants housed in a New York State zoo for 25 yr revealed live mites (Loxoaneotus bassoni). The cytologic examination demonstrated no evidence of inflammation or infection. Both elephants were asymptomatic with normal hemograms and serum chemistry panels. A diagnosis of otoacariasis was made. Each elephant was treated six times with 5 ml of 1% ivermectin syrup instilled in each ear canal once every 2 wk. Microscopic examinations of clear mucus collected from each elephant's ear canals 9 days after the first instillation of ivermectin were negative for any life stages of ear mites. Microscopic examinations of mucus collected from both elephants' ear canals at 6, 11, and 16 wk, as well as annually post-treatment for 7 yr, confirmed eradication of the ear mites. The L. bassoni ear mite was first identified in the external ear canals of wild, asymptomatic, lesion-free, African elephants culled in Kruger National Park in South Africa. However, a new species in the same genus of mites (Loxoanoetus lenae) was identified at the necropsy of an 86-yr-old Asian elephant (Elephas maximus) living in a circus in Australia. The autopsy revealed a marked, ballooning distension of bone around the left external acoustic meatus, suggestive of mite-induced otitis externa, as seen in cattle infested with ear mites (Raillieta auris). Elephant health care providers should identify the prevalence of, and consider treatment of, elephants in their care infested with ear mites, given the possible risk for adverse health effects.

  14. Scabies Mites Alter the Skin Microbiome and Promote Growth of Opportunistic Pathogens in a Porcine Model

    PubMed Central

    Swe, Pearl M.; Zakrzewski, Martha; Kelly, Andrew; Krause, Lutz; Fischer, Katja

    2014-01-01

    Background The resident skin microbiota plays an important role in restricting pathogenic bacteria, thereby protecting the host. Scabies mites (Sarcoptes scabiei) are thought to promote bacterial infections by breaching the skin barrier and excreting molecules that inhibit host innate immune responses. Epidemiological studies in humans confirm increased incidence of impetigo, generally caused by Staphylococcus aureus and Streptococcus pyogenes, secondary to the epidermal infestation with the parasitic mite. It is therefore possible that mite infestation could alter the healthy skin microbiota making way for the opportunistic pathogens. A longitudinal study to test this hypothesis in humans is near impossible due to ethical reasons. In a porcine model we generated scabies infestations closely resembling the disease manifestation in humans and investigated the scabies associated changes in the skin microbiota over the course of a mite infestation. Methodology/Principal Findings In a 21 week trial, skin scrapings were collected from pigs infected with S. scabies var. suis and scabies-free control animals. A total of 96 skin scrapings were collected before, during infection and after acaricide treatment, and analyzed by bacterial 16S rDNA tag-encoded FLX-titanium amplicon pyrosequencing. We found significant changes in the epidermal microbiota, in particular a dramatic increase in Staphylococcus correlating with the onset of mite infestation in animals challenged with scabies mites. This increase persisted beyond treatment from mite infection and healing of skin. Furthermore, the staphylococci population shifted from the commensal S. hominis on the healthy skin prior to scabies mite challenge to S. chromogenes, which is increasingly recognized as being pathogenic, coinciding with scabies infection in pigs. In contrast, all animals in the scabies-free cohort remained relatively free of Staphylococcus throughout the trial. Conclusions/Significance This is the first

  15. Pharmacokinetics and penetration of ceftazidime and avibactam into epithelial lining fluid in thigh- and lung-infected mice.

    PubMed

    Berkhout, Johanna; Melchers, Maria J; van Mil, Anita C; Seyedmousavi, Seyedmojtaba; Lagarde, Claudia M; Nichols, Wright W; Mouton, Johan W

    2015-04-01

    Ceftazidime and the β-lactamase inhibitor avibactam constitute a new, potentially highly active combination in the battle against extended-spectrum-β-lactamase (ESBL)-producing bacteria. To determine possible clinical use, it is important to know the pharmacokinetic profiles of the compounds related to each other in plasma and the different compartments of infection in experimentally infected animals and in humans. We used a neutropenic murine thigh infection model and lung infection model to study pharmacokinetics in plasma and epithelial lining fluid (ELF). Mice were infected with ca. 10(6) CFU of Pseudomonas aeruginosa intramuscularly into the thigh or intranasally to cause pneumonia and were given 8 different (single) subcutaneous doses of ceftazidime and avibactam in various combined concentrations, ranging from 1 to 128 mg/kg of body weight in 2-fold increases. Concomitant samples of serum and bronchoalveolar lavage fluid were taken at up to 12 time points until 6 h after administration. Pharmacokinetics of both compounds were linear and dose proportional in plasma and ELF and were independent of the infection type, with estimated half-lives (standard deviations [SD]) in plasma of ceftazidime of 0.28 (0.02) h and of avibactam of 0.24 (0.04) h and volumes of distribution of 0.80 (0.14) and 1.18 (0.34) liters/kg. The ELF-plasma (area under the concentration-time curve [AUC]) ratios (standard errors [SE]) were 0.24 (0.03) for total ceftazidime and 0.27 (0.03) for unbound ceftazidime; for avibactam, the ratios were 0.20 (0.02) and 0.22 (0.02), respectively. No pharmacokinetic interaction between ceftazidime and avibactam was observed. Ceftazidime and avibactam showed linear plasma pharmacokinetics that were independent of the dose combinations used or the infection site in mice. Assuming pharmacokinetic similarity in humans, this indicates that similar dose ratios of ceftazidime and avibactam could be used for different types and sites of infection. PMID

  16. Genotypic and phenotypic variation in Pseudomonas aeruginosa reveals signatures of secondary infection and mutator activity in certain cystic fibrosis patients with chronic lung infections.

    PubMed

    Warren, Ashley E; Boulianne-Larsen, Carla M; Chandler, Christine B; Chiotti, Kami; Kroll, Evgueny; Miller, Scott R; Taddei, Francois; Sermet-Gaudelus, Isabelle; Ferroni, Agnes; McInnerney, Kathleen; Franklin, Michael J; Rosenzweig, Frank

    2011-12-01

    Evolutionary adaptation of Pseudomonas aeruginosa to the cystic fibrosis lung is limited by genetic variation, which depends on rates of horizontal gene transfer and mutation supply. Because each may increase following secondary infection or mutator emergence, we sought to ascertain the incidence of secondary infection and genetic variability in populations containing or lacking mutators. Forty-nine strains collected over 3 years from 16 patients were phenotyped for antibiotic resistance and mutator status and were genotyped by repetitive-sequence PCR (rep-PCR), pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST). Though phenotypic and genetic polymorphisms were widespread and clustered more strongly within than between longitudinal series, their distribution revealed instances of secondary infection. Sequence data, however, indicated that interlineage recombination predated initial strain isolation. Mutator series were more likely to be multiply antibiotic resistant, but not necessarily more variable in their nucleotide sequences, than nonmutators. One mutator and one nonmutator series were sequenced at mismatch repair loci and analyzed for gene content using DNA microarrays. Both were wild type with respect to mutL, but mutators carried an 8-bp mutS deletion causing a frameshift mutation. Both series lacked 126 genes encoding pilins, siderophores, and virulence factors whose inactivation has been linked to adaptation during chronic infection. Mutators exhibited loss of severalfold more genes having functions related to mobile elements, motility, and attachment. A 105-kb, 86-gene deletion was observed in one nonmutator that resulted in loss of virulence factors related to pyoverdine synthesis and elements of the multidrug efflux regulon. Diminished DNA repair activity may facilitate but not be absolutely required for rapid evolutionary change.

  17. Granzyme A Is Expressed in Mouse Lungs during Mycobacterium tuberculosis Infection but Does Not Contribute to Protection In Vivo

    PubMed Central

    Uranga, Santiago; Marinova, Dessislava; Martin, Carlos; Pardo, Julián; Aguilo, Nacho

    2016-01-01

    Granzyme A, a serine protease expressed in the granules of cytotoxic T and Natural Killer cells, is involved in the generation of pro-inflammatory cytokines by macrophages. Granzyme A has been described to induce in macrophages in vitro the activation of pro-inflammatory pathways that impair intracellular mycobacterial replication. In the present study, we explored the physiological relevance of Granzyme A in the control of pulmonary Mycobacterium tuberculosis infection in vivo. Our results show that, even though Granzyme A is expressed by cytotoxic cells from mouse lungs during pulmonary infection, its deficiency in knockout mice does not have an effect in the control of M. tuberculosis infection. In addition our findings indicate that absence of Granzyme A does not affect the protection conferred by the live-attenuated M. tuberculosis vaccine MTBVAC. Altogether, our findings are in apparent contradiction with previously published in vitro results and suggest that Granzyme A does not have a crucial role in vivo in the protective response to tuberculosis. PMID:27055232

  18. Granzyme A Is Expressed in Mouse Lungs during Mycobacterium tuberculosis Infection but Does Not Contribute to Protection In Vivo.

    PubMed

    Uranga, Santiago; Marinova, Dessislava; Martin, Carlos; Pardo, Julián; Aguilo, Nacho

    2016-01-01

    Granzyme A, a serine protease expressed in the granules of cytotoxic T and Natural Killer cells, is involved in the generation of pro-inflammatory cytokines by macrophages. Granzyme A has been described to induce in macrophages in vitro the activation of pro-inflammatory pathways that impair intracellular mycobacterial replication. In the present study, we explored the physiological relevance of Granzyme A in the control of pulmonary Mycobacterium tuberculosis infection in vivo. Our results show that, even though Granzyme A is expressed by cytotoxic cells from mouse lungs during pulmonary infection, its deficiency in knockout mice does not have an effect in the control of M. tuberculosis infection. In addition our findings indicate that absence of Granzyme A does not affect the protection conferred by the live-attenuated M. tuberculosis vaccine MTBVAC. Altogether, our findings are in apparent contradiction with previously published in vitro results and suggest that Granzyme A does not have a crucial role in vivo in the protective response to tuberculosis. PMID:27055232

  19. Structural Mechanisms of Inactivation in Scabies Mite Serine Protease Paralogues

    SciTech Connect

    Fischer, Katja; Langendorf, Christopher G.; Irving, James A.; Reynolds, Simone; Willis, Charlene; Beckham, Simone; Law, Ruby H.P.; Yang, Sundy; Bashtannyk-Puhalovich, Tanya A.; McGowan, Sheena; Whisstock, James C.; Pike, Robert N.; Kemp, David J.; Buckle, Ashley M.

    2009-08-07

    The scabies mite (Sarcoptes scabiei) is a parasite responsible for major morbidity in disadvantaged communities and immuno-compromised patients worldwide. In addition to the physical discomfort caused by the disease, scabies infestations facilitate infection by Streptococcal species via skin lesions, resulting in a high prevalence of rheumatic fever/heart disease in affected communities. The scabies mite produces 33 proteins that are closely related to those in the dust mite group 3 allergen and belong to the S1-like protease family (chymotrypsin-like). However, all but one of these molecules contain mutations in the conserved active-site catalytic triad that are predicted to render them catalytically inactive. These molecules are thus termed scabies mite inactivated protease paralogues (SMIPPs). The precise function of SMIPPs is unclear; however, it has been suggested that these proteins might function by binding and protecting target substrates from cleavage by host immune proteases, thus preventing the host from mounting an effective immune challenge. In order to begin to understand the structural basis for SMIPP function, we solved the crystal structures of SMIPP-S-I1 and SMIPP-S-D1 at 1.85 {angstrom} and 2.0 {angstrom} resolution, respectively. Both structures adopt the characteristic serine protease fold, albeit with large structural variations over much of the molecule. In both structures, mutations in the catalytic triad together with occlusion of the S1 subsite by a conserved Tyr200 residue is predicted to block substrate ingress. Accordingly, we show that both proteases lack catalytic function. Attempts to restore function (via site-directed mutagenesis of catalytic residues as well as Tyr200) were unsuccessful. Taken together, these data suggest that SMIPPs have lost the ability to bind substrates in a classical 'canonical' fashion, and instead have evolved alternative functions in the lifecycle of the scabies mite.

  20. Influenza A Virus Dysregulates Host Histone Deacetylase 1 That Inhibits Viral Infection in Lung Epithelial Cells

    PubMed Central

    Nagesh, Prashanth Thevkar

    2016-01-01

    ABSTRACT Viruses dysregulate the host factors that inhibit virus infection. Here, we demonstrate that human enzyme, histone deacetylase 1 (HDAC1) is a new class of host factor that inhibits influenza A virus (IAV) infection, and IAV dysregulates HDAC1 to efficiently replicate in epithelial cells. A time-dependent decrease in HDAC1 polypeptide level was observed in IAV-infected cells, reducing to <50% by 24 h of infection. A further depletion (97%) of HDAC1 expression by RNA interference increased the IAV growth kinetics, increasing it by >3-fold by 24 h and by >6-fold by 48 h of infection. Conversely, overexpression of HDAC1 decreased the IAV infection by >2-fold. Likewise, a time-dependent decrease in HDAC1 activity, albeit with slightly different kinetics to HDAC1 polypeptide reduction, was observed in infected cells. Nevertheless, a further inhibition of deacetylase activity increased IAV infection in a dose-dependent manner. HDAC1 is an important host deacetylase and, in addition to its role as a transcription repressor, HDAC1 has been lately described as a coactivator of type I interferon response. Consistent with this property, we found that inhibition of deacetylase activity either decreased or abolished the phosphorylation of signal transducer and activator of transcription I (STAT1) and expression of interferon-stimulated genes, IFITM3, ISG15, and viperin in IAV-infected cells. Furthermore, the knockdown of HDAC1 expression in infected cells decreased viperin expression by 58% and, conversely, the overexpression of HDAC1 increased it by 55%, indicating that HDAC1 is a component of IAV-induced host type I interferon antiviral response. IMPORTANCE Influenza A virus (IAV) continues to significantly impact global public health by causing regular seasonal epidemics, occasional pandemics, and zoonotic outbreaks. IAV is among the successful human viral pathogens that has evolved various strategies to evade host defenses, prevent the development of a universal

  1. Fat-associated lymphoid clusters control local IgM secretion during pleural infection and lung inflammation.

    PubMed

    Jackson-Jones, Lucy H; Duncan, Sheelagh M; Magalhaes, Marlène S; Campbell, Sharon M; Maizels, Rick M; McSorley, Henry J; Allen, Judith E; Bénézech, Cécile

    2016-01-01

    Fat-associated lymphoid clusters (FALC) are inducible structures that support rapid innate-like B-cell immune responses in the serous cavities. Little is known about the physiological cues that activate FALCs in the pleural cavity and more generally the mechanisms controlling B-cell activation in FALCs. Here we show, using separate models of pleural nematode infection with Litomosoides sigmodontis and Altenaria alternata induced acute lung inflammation, that inflammation of the pleural cavity rapidly activates mediastinal and pericardial FALCs. IL-33 produced by FALC stroma is crucial for pleural B1-cell activation and local IgM secretion. However, B1 cells are not the direct target of IL-33, which instead requires IL-5 for activation. Moreover, lung inflammation leads to increased IL-5 production by type 2 cytokine-producing innate lymphoid cells (ILC2) in the FALC. These findings reveal a link between inflammation, IL-33 release by FALC stromal cells, ILC2 activation and pleural B-cell activation in FALCs, resulting in local and antigen-specific IgM production. PMID:27582256

  2. Three-Dimensionally Engineered Normal Human Lung Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas J.; McCarthy, M.; Lin, Y-H.; Deatly, A. M.

    2008-01-01

    In vitro three-dimensional (3D) human lung epithelio-mesenchymal tissue-like assemblies (3D hLEM TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and the detection of membrane bound glycoproteins over time confirm productive infection with the virus. Therefore, we assert TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host s immune system.

  3. Fat-associated lymphoid clusters control local IgM secretion during pleural infection and lung inflammation

    PubMed Central

    Jackson-Jones, Lucy H.; Duncan, Sheelagh M.; Magalhaes, Marlène S.; Campbell, Sharon M.; Maizels, Rick M.; McSorley, Henry J.; Allen, Judith E.; Bénézech, Cécile

    2016-01-01

    Fat-associated lymphoid clusters (FALC) are inducible structures that support rapid innate-like B-cell immune responses in the serous cavities. Little is known about the physiological cues that activate FALCs in the pleural cavity and more generally the mechanisms controlling B-cell activation in FALCs. Here we show, using separate models of pleural nematode infection with Litomosoides sigmodontis and Altenaria alternata induced acute lung inflammation, that inflammation of the pleural cavity rapidly activates mediastinal and pericardial FALCs. IL-33 produced by FALC stroma is crucial for pleural B1-cell activation and local IgM secretion. However, B1 cells are not the direct target of IL-33, which instead requires IL-5 for activation. Moreover, lung inflammation leads to increased IL-5 production by type 2 cytokine-producing innate lymphoid cells (ILC2) in the FALC. These findings reveal a link between inflammation, IL-33 release by FALC stromal cells, ILC2 activation and pleural B-cell activation in FALCs, resulting in local and antigen-specific IgM production. PMID:27582256

  4. Association of a PAI-1 Gene Polymorphism and Early Life Infections with Asthma Risk, Exacerbations, and Reduced Lung Function

    PubMed Central

    Kim, Dong Young; Oh, Sam S.; Torgerson, Dara R.; Pino-Yanes, Maria; Hu, Donglei; Sen, Saunak; Huntsman, Scott; Eng, Celeste; Farber, Harold J.; Rodriguez-Cintron, William; Rodriguez-Santana, Jose R.; Serebrisky, Denise; Thyne, Shannon M.; Borrell, Luisa N.; Williams, L. Keoki; DuPont, William; Seibold, Max A.; Burchard, Esteban G.; Avila, Pedro C.; Kumar, Rajesh

    2016-01-01

    Background Plasminogen activator inhibitor-1 (PAI-1) is induced in airways by virus and may mediate asthmatic airway remodeling. We sought to evaluate if genetic variants and early life lower respiratory infections jointly affect asthma risk. Methods We included Latino children, adolescents, and young adults aged 8–21 years (1736 subjects with physician-diagnosed asthma and 1747 healthy controls) from five U.S. centers and Puerto Rico after excluding subjects with incomplete clinical or genetic data. We evaluated the independent and joint effects of a PAI-1 gain of function polymorphism and bronchiolitis / Respiratory Syncytial Virus (RSV) or other lower respiratory infections (LRI) within the first 2 years of life on asthma risk, asthma exacerbations and lung function. Results RSV infection (OR 9.9, 95%CI 4.9–20.2) and other LRI (OR 9.1, 95%CI 7.2–11.5) were independently associated with asthma, but PAI-1 genotype was not. There were joint effects on asthma risk for both genotype-RSV (OR 17.7, 95% CI 6.3–50.2) and genotype-LRI (OR 11.7, 95% CI 8.8–16.4). A joint effect of genotype-RSV resulted in a 3.1-fold increased risk for recurrent asthma hospitalizations. In genotype-respiratory infection joint effect analysis, FEV1% predicted and FEV1/FVC % predicted were further reduced in the genotype-LRI group (β -2.1, 95% CI -4.0 to -0.2; β -2.0, 95% CI -3.1 to -0.8 respectively). Similarly, lower FEV1% predicted was noted in genotype-RSV group (β -3.1, 95% CI -6.1 to -0.2) with a trend for lower FEV1/FVC % predicted. Conclusions A genetic variant of PAI-1 together with early life LRI such as RSV bronchiolitis is associated with an increased risk of asthma, morbidity, and reduced lung function in this Latino population. PMID:27556405

  5. Lung Diseases and Conditions

    MedlinePlus

    ... Share this page from the NHLBI on Twitter. Lung Diseases and Conditions Breathing is a complex process. ... your bronchial tubes ( bronchitis ) or deep in your lungs ( pneumonia ). These infections cause a buildup of mucus ...

  6. Adenovirus vector infection of non-small-cell lung cancer cells is a trigger for multi-drug resistance mediated by P-glycoprotein.

    PubMed

    Tomono, Takumi; Kajita, Masahiro; Yano, Kentaro; Ogihara, Takuo

    2016-08-01

    P-glycoprotein (P-gp) is an ATP-binding cassette protein involved in cancer multi-drug resistance (MDR). It has been reported that infection with some bacteria and viruses induces changes in the activities of various drug-metabolizing enzymes and transporters, including P-gp. Although human adenoviruses (Ad) cause the common cold, the effect of Ad infection on MDR in cancer has not been established. In this study, we investigated whether Ad infection is a cause of MDR in A549, H441 and HCC827 non-small-cell lung cancer (NSCLC) cell lines, using an Ad vector system. We found that Ad vector infection of NSCLC cell lines induced P-gp mRNA expression, and the extent of induction was dependent on the number of Ad vector virus particles and the infection time. Heat-treated Ad vector, which is not infectious, did not alter P-gp mRNA expression. Uptake experiments with doxorubicin (DOX), a P-gp substrate, revealed that DOX accumulation was significantly decreased in Ad vector-infected A549 cells. The decrease of DOX uptake was blocked by verapamil, a P-gp inhibitor. Our results indicated that Ad vector infection of NSCLC cells caused MDR mediated by P-gp overexpression. The Ad vector genome sequence is similar to that of human Ad, and therefore human Ad infection of lung cancer patients may lead to chemoresistance in the clinical environment.

  7. Differential effect of plasma and red blood cell transfusion on acute lung injury and infection risk following liver transplantation

    PubMed Central

    Benson, Alexander B.; Burton, James R.; Austin, Gregory L.; Biggins, Scott W.; Zimmerman, Michael A.; Kam, Igal; Mandell, Susan; Silliman, Christopher C.; Rosen, Hugo; Moss, Marc

    2010-01-01

    Rationale Patients with chronic liver disease are at an increased risk of developing transfusion-associated acute lung injury (TRALI) from plasma containing blood products. Similarly, red blood cell transfusions have been associated with post-operative and nosocomial infections in surgical and critical care populations. Patients undergoing liver transplantation receive a large amount of cellular and plasma containing blood products, but it is presently unclear which blood components are associated with these post-operative complications. Results A retrospective cohort study of 525 consecutive liver transplant patients revealed a peri-operative TRALI incidence of 1.3% (7/525), 95%CI [0.6%–2.7%], associated with an increased hospital mortality (28.6% (2/7) vs. 2.9% (15/518), p=0.02) and intensive care unit (ICU) length of stay (2 days, [1–11] vs. 0 days [0–2], 0.03). Only high plasma containing blood products (plasma and platelets) were associated with the development of TRALI. A total of 14.3% (74/525) of patients developed a post-operative infection which was also associated with an increased in-hospital mortality (10.8% (8/74) vs. 2.0% (9/451), p < 0.01) and prolonged length of stay. Multivariate logistic regression identified the number of red blood cell units transfused (adj OR 1.08 95%CI [1.02–1.14], p<0.01), the presence of peri-operative renal dysfunction and re-operation to be significantly associated with post-operative infection. Conclusions Patients undergoing liver transplantation are at high risk of developing post-operative complications from blood transfusion. Plasma containing blood products were associated with the development of TRALI while red blood cells were associated with the development of post-operative infection in a dose dependent manner. PMID:21280188

  8. Depletion of M. tuberculosis GlmU from Infected Murine Lungs Effects the Clearance of the Pathogen

    PubMed Central

    Soni, Vijay; Upadhayay, Sandeep; Suryadevara, Priyanka; Samla, Ganesh; Singh, Archana; Yogeeswari, Perumal; Sriram, Dharmarajan; Nandicoori, Vinay Kumar

    2015-01-01

    M. tuberculosis N-acetyl-glucosamine-1-phosphate uridyltransferase (GlmUMtb) is a bi-functional enzyme engaged in the synthesis of two metabolic intermediates N-acetylglucosamine-1-phosphate (GlcNAc-1-P) and UDP-GlcNAc, catalyzed by the C- and N-terminal domains respectively. UDP-GlcNAc is a key metabolite essential for the synthesis of peptidoglycan, disaccharide linker, arabinogalactan and mycothiols. While glmUMtb was predicted to be an essential gene, till date the role of GlmUMtb in modulating the in vitro growth of Mtb or its role in survival of pathogen ex vivo / in vivo have not been deciphered. Here we present the results of a comprehensive study dissecting the role of GlmUMtb in arbitrating the survival of the pathogen both in vitro and in vivo. We find that absence of GlmUMtb leads to extensive perturbation of bacterial morphology and substantial reduction in cell wall thickness under normoxic as well as hypoxic conditions. Complementation studies show that the acetyl- and uridyl- transferase activities of GlmUMtb are independently essential for bacterial survival in vitro, and GlmUMtb is also found to be essential for mycobacterial survival in THP-1 cells as well as in guinea pigs. Depletion of GlmUMtb from infected murine lungs, four weeks post infection, led to significant reduction in the bacillary load. The administration of Oxa33, a novel oxazolidine derivative that specifically inhibits GlmUMtb, to infected mice resulted in significant decrease in the bacillary load. Thus our study establishes GlmUMtb as a strong candidate for intervention measures against established tuberculosis infections. PMID:26489015

  9. Deficiency of autophagy protein Map1-LC3b mediates IL-17-dependent lung pathology during respiratory viral infection via ER stress associated IL-1

    PubMed Central

    Reed, Michelle; Morris, Susan H.; Owczarczyk, Anna B.; Lukacs, Nicholas W.

    2015-01-01

    While recent studies suggest that IL-1β production is modulated by macroautophagy or sensors of ER stress upon pro-inflammatory insult, autophagy and IL-1β production during viral infection has not been fully investigated. This was addressed using respiratory syncytial virus (RSV), which is associated with lung immunopathology, IL-1, and IL-17a secretion in severely infected patients. Mice deficient in the autophagy-associated protein Map1-LC3b (LC3b−/−) developed increased IL-17a-dependent lung pathology upon infection. RSV-infected LC3b−/− DCs fail to upregulate autophagosome formation, secrete IL-1β and IL-6, and elicit IL-17a production from CD4+ T cells. Bone marrow chimeras revealed both structural and hematopoietic LC3b deficiency contribute to the development of IL-17a-dependent lung pathology in vivo. Further investigation revealed airway epithelium as the primary source of IL-1β during infection, while inhibition of the ER-stress sensor IRE-1 in primary airway epithelial cells reduced IL-1β production identifying a primary ER stress pathway. Finally, blockade of IL-1 receptor signaling in RSV-infected LC3b−/− mice abolished IL-17a-dependent lung pathology. These findings provide novel mechanistic insight into the contribution of autophagy- and ER stress-dependent cytokine production that initiate and maintain aberrant Th17 responses, while identifying IL-1 as a potential therapeutic target in the treatment of severe respiratory viral infections. PMID:25669150

  10. Deficiency of autophagy protein Map1-LC3b mediates IL-17-dependent lung pathology during respiratory viral infection via ER stress-associated IL-1.

    PubMed

    Reed, M; Morris, S H; Owczarczyk, A B; Lukacs, N W

    2015-09-01

    While recent studies suggest that interleukin (IL)-1β production is modulated by macroautophagy or sensors of endoplasmic reticulum (ER) stress upon pro-inflammatory insult, autophagy and IL-1β production during viral infection has not been fully investigated. This was addressed using respiratory syncytial virus (RSV), which is associated with lung immunopathology, IL-1, and IL-17a secretion in severely infected patients. Mice deficient in the autophagy-associated protein Map1-LC3b (LC3b(-/-)) developed increased IL-17a-dependent lung pathology upon infection. RSV-infected LC3b(-/-) dendritic cells (DCs) fail to upregulate autophagosome formation, secrete IL-1β and IL-6, and elicit IL-17a production from CD4+ T cells. Bone marrow chimeras revealed that both structural and hematopoietic LC3b deficiency contribute to the development of IL-17a-dependent lung pathology in vivo. Further investigation revealed airway epithelium as the primary source of IL-1β during infection, whereas inhibition of the ER-stress sensor inositol-requiring protein-1 in primary airway epithelial cells reduced IL-1β production identifying a primary ER stress pathway. Finally, blockade of IL-1 receptor signaling in RSV-infected LC3b(-/-) mice abolished IL-17a-dependent lung pathology. These findings provide novel mechanistic insight into the contribution of autophagy- and ER stress-dependent cytokine production that initiate and maintain aberrant Th17 responses, while identifying IL-1 as a potential therapeutic target in the treatment of severe respiratory viral infections. PMID:25669150

  11. Bone marrow transplantation alters lung antigen presenting cells to promote TH17 response and the development of pneumonitis and fibrosis following gammaherpesvirus infection

    PubMed Central

    Zhou, Xiaofeng; Loomis-King, Hillary; Gurczynski, Stephen J.; Wilke, Carol A.; Konopka, Kristine E.; Ptaschinski, Catherine; Coomes, Stephanie M; Iwakura, Yoichiro; van Dyk, Linda F.; Lukacs, Nicholas W.; Moore, Bethany B.

    2015-01-01

    Hematopoietic stem cell transplantation (HSCT) efficacy is limited by numerous pulmonary complications. We developed a model of syngeneic bone marrow transplant (BMT) followed by infection with murine gamma herpesvirus (γHV-68) that results in pneumonitis and fibrosis and mimics human “non-infectious” HSCT complications. BMT mice experience increased early lytic replication, but establish viral latency by 21 days post infection (dpi). CD4 T cells in BMT mice are skewed towards IL-17A rather than IFN-γ production. Transplantation of bone marrow from Il-17a−/− donors or treatment with anti-IL-17A neutralization antibodies at late stages attenuates pneumonitis and fibrosis in infected BMT mice, suggesting that hematopoietic-derived IL-17A is essential for development of pathology. IL-17A directly influences activation and extracellular matrix production by lung mesenchymal cells. Lung CD11c+ cells of BMT mice secrete more TGF-β1, and pro-TH17 mRNAs for IL-23 and IL-6, and less TH1-promoting cytokine mRNA for IFN-γ but slightly more IL-12 mRNA in response to viral infection. Adoptive transfer of non-BMT lung CD11c-enriched cells restores robust TH1 response and suppresses aberrant TH17 response in BMT mice to improve lung pathology. Our data suggest “non-infectious” HSCT lung complications may reflect preceding viral infections and demonstrate that IL-17A neutralization may offer therapeutic advantage even after disease onset. PMID:26376362

  12. In vitro efficacy of ByeMite and Mite-Stop on developmental stages of the red chicken mite Dermanyssus gallinae.

    PubMed

    Abdel-Ghaffar, Fathy; Semmler, Margit; Al-Rasheid, Khaled; Mehlhorn, Heinz

    2009-10-01

    The present in vitro study shows the efficacy of two antimite products (ByeMite = phoxim, Mite-Stop = neem seed extract) against all developing stages of the important red chicken mite Dermanyssus gallinae (obtained at two farms in France and Germany). While permanent contact with the active compound led to an efficacy of 100% in the case of Mite-Stop on mites in both farms, there was only a 96.2% killing effect of ByeMite on the mites of the French farm. Even short contacts of only 4 s killed 100% of mites in the case of Mite-Stop at the French farm and only 84.5% in the German farm. ByeMite, on the other hand, killed only 27.8% (Germany) and 30% (France) when mites got the chance to escape from the treated grounds to untreated ones. When using only the half doses of both products, Mite-Stop(R) still reached, after permanent contact, 100% activity on the German farm and 98.2% in France, while ByeMite killed 93.8% (Germany) and 90.6% (France). Short contact to half doses of course reduced the activity of both products (Mite-Stop = 59.3% in France, 22.1% in Germany; ByeMite = 28.8% in France, 18.8% in Germany). With respect to the fumigant activity of the products, the strains of D. gallinae reacted differently. While Mite-Stop(R) showed a clear fumigant activity in the case of the German mites, this product did not affect the French mites by air distribution, neither did ByeMite in both cases. Therefore, mites have to come in contact with both products. Against Mite-Stop, there was apparently no resistance and low doses have high efficacy after even short contacts, which regularly occur in a treated stable, where mites have the chance to leave treated places to untreated hidden spots.

  13. Viral epidemiology of the adult Apis Mellifera infested by the Varroa destructor mite.

    PubMed

    Bernardi, Sara; Venturino, Ezio

    2016-05-01

    The ectoparasitic mite Varroa destructor has become one of the major worldwide threats for apiculture. Varroa destructor attacks the honey bee Apis mellifera weakening its host by sucking hemolymph. However, the damage to bee colonies is not strictly related to the parasitic action of the mite but it derives, above all, from its action as vector increasing the transmission of many viral diseases such as acute paralysis (ABPV) and deformed wing viruses (DWV), that are considered among the main causes of CCD (Colony Collapse Disorder). In this work we discuss an [Formula: see text] model that describes how the presence of the mite affects the epidemiology of these viruses on adult bees. The acronym [Formula: see text] means that the disease affects both populations. In fact it accounts for the bee and mite populations, that are each divided among the S (susceptible) and I (infected) states. We characterize the system behavior, establishing that ultimately either only healthy bees survive, or the disease becomes endemic and mites are wiped out. Another dangerous alternative is the Varroa invasion scenario with the extinction of healthy bees. The final possible configuration is the coexistence equilibrium in which honey bees share their infected hive with mites. The analysis is in line with some observed facts in natural honey bee colonies. Namely, these diseases are endemic. Further, if the mite population is present, necessarily the viral infection occurs. The findings of this study indicate that a low horizontal transmission rate of the virus among honey bees in beehives will help in protecting bee colonies from Varroa infestation and viral epidemics. PMID:27441276

  14. Viral epidemiology of the adult Apis Mellifera infested by the Varroa destructor mite.

    PubMed

    Bernardi, Sara; Venturino, Ezio

    2016-05-01

    The ectoparasitic mite Varroa destructor has become one of the major worldwide threats for apiculture. Varroa destructor attacks the honey bee Apis mellifera weakening its host by sucking hemolymph. However, the damage to bee colonies is not strictly related to the parasitic action of the mite but it derives, above all, from its action as vector increasing the transmission of many viral diseases such as acute paralysis (ABPV) and deformed wing viruses (DWV), that are considered among the main causes of CCD (Colony Collapse Disorder). In this work we discuss an [Formula: see text] model that describes how the presence of the mite affects the epidemiology of these viruses on adult bees. The acronym [Formula: see text] means that the disease affects both populations. In fact it accounts for the bee and mite populations, that are each divided among the S (susceptible) and I (infected) states. We characterize the system behavior, establishing that ultimately either only healthy bees survive, or the disease becomes endemic and mites are wiped out. Another dangerous alternative is the Varroa invasion scenario with the extinction of healthy bees. The final possible configuration is the coexistence equilibrium in which honey bees share their infected hive with mites. The analysis is in line with some observed facts in natural honey bee colonies. Namely, these diseases are endemic. Further, if the mite population is present, necessarily the viral infection occurs. The findings of this study indicate that a low horizontal transmission rate of the virus among honey bees in beehives will help in protecting bee colonies from Varroa infestation and viral epidemics.

  15. Molecular Prevalence of Acarapis Mite Infestations in Honey Bees in Korea

    PubMed Central

    Ahn, Ah-Jin; Ahn, Kyu-Sung; Noh, Jin-Hyeong; Kim, Young-Ha; Yoo, Mi-Sun; Kang, Seung-Won; Yu, Do-Hyeon; Shin, Sung Shik

    2015-01-01

    Acarapis mites, including Acarapis woodi, Acarapis externus, and Acarapis dorsalis, are parasites of bees which can cause severe damage to the bee industry by destroying colonies and decreasing honey production. All 3 species are prevalent throughout many countries including UK, USA, Iran, Turkey, China, and Japan. Based on previous reports of Acarapis mites occurring in northeast Asia, including China and Japan, we investigated a survey of Acarapis mite infestations in honey bees in Korean apiaries. A total of 99 colonies of Apis mellifera were sampled from 5 provinces. The head and thorax of 20 bees from each colony were removed for DNA extraction. PCR assays were performed with 3 primer sets, including T, A, and K primers. Results indicated that 42.4% (42/99) of samples were Acarapis-positive by PCR assay which were sequenced to identify species. Each sequence showed 92.6-99.3% homology with reference sequences. Based on the homology, the number of colonies infected with A. dorsalis was 32 which showed the highest infection rate among the 3 species, while the number of colonies infected with A. externus and A. woodi was 9 and 1, respectively. However, none of the Acarapis mites were morphologically detected. This result could be explained that all apiaries in the survey used acaricides against bee mites such as Varroa destructor and Tropilaelaps clareae which also affect against Acarapis mites. Based on this study, it is highly probable that Acarapis mites as well as Varroa and Tropilaelaps could be prevalent in Korean apiaries. PMID:26174825

  16. Three Phases of CD8 T Cell Response in the Lung Following H1N1 Influenza Infection and Sphingosine 1 Phosphate Agonist Therapy

    PubMed Central

    Matheu, Melanie P.; Teijaro, John R.; Walsh, Kevin B.; Greenberg, Milton L.; Marsolais, David; Parker, Ian; Rosen, Hugh; Oldstone, Michael B A.; Cahalan, Michael D.

    2013-01-01

    Influenza-induced lung edema and inflammation are exacerbated by a positive feedback loop of cytokine and chemokine production termed a ‘cytokine storm’, a hallmark of increased influenza-related morbidity and mortality. Upon infection, an immune response is rapidly initiated in the lungs and draining lymph node, leading to expansion of virus-specific effector cells. Using two-photon microscopy, we imaged the dynamics of dendritic cells (DC) and virus-specific eGFP+CD8+ T cells in the lungs and draining mediastinal lymph nodes during the first two weeks following influenza infection. Three distinct phases of T cell and CD11c+ DC behavior were revealed: 1) Priming, facilitated by the arrival of lung DCs in the lymph node and characterized by antigen recognition and expansion of antigen-specific CD8+ T cells; asymmetric T cell division in contact with DCs was frequently observed. 2) Clearance, during which DCs re-populate the lung and T cells leave the draining lymph node and re-enter the lung tissue where enlarged, motile T cells come into contact with DCs and form long-lived interactions. 3) Maintenance, characterized by T-cell scanning of the lung tissue and dissociation from local antigen presenting cells; the T cells spend less time in association with DCs and migrate rapidly on collagen. A single dose of a sphingosine-1-phosphate receptor agonist, AAL-R, sufficient to suppress influenza-induced cytokine-storm, altered T cell and DC behavior during influenza clearance, delaying T cell division, cellular infiltration in the lung, and suppressing T-DC interactions in the lung. Our results provide a detailed description of T cell and DC choreography and dynamics in the lymph node and the lung during influenza infection. In addition, we suggest that phase lags in T cell and DC dynamics induced by targeting S1P receptors in vivo may attenuate the intensity of the immune response and can be manipulated for therapeutic benefit. PMID:23533579

  17. Lung CD8+ T Cell Impairment Occurs during Human Metapneumovirus Infection despite Virus-Like Particle Induction of Functional CD8+ T Cells

    PubMed Central

    Wen, Sherry C.; Schuster, Jennifer E.; Gilchuk, Pavlo; Boyd, Kelli L.; Joyce, Sebastian

    2015-01-01

    ABSTRACT Human metapneumovirus (HMPV) is a major cause of respiratory disease in infants, the elderly, and immunocompromised individuals worldwide. There is currently no licensed HMPV vaccine. Virus-like particles (VLPs) are an attractive vaccine candidate because they are noninfectious and elicit a neutralizing antibody response. However, studies show that serum neutralizing antibodies are insufficient for complete protection against reinfection and that adaptive T cell immunity is important for viral clearance. HMPV and other respiratory viruses induce lung CD8+ T cell (TCD8) impairment, mediated by programmed death 1 (PD-1). In this study, we generated HMPV VLPs by expressing the fusion and matrix proteins in mammalian cells and tested whether VLP immunization induces functional HMPV-specific TCD8 responses in mice. C57BL/6 mice vaccinated twice with VLPs and subsequently challenged with HMPV were protected from lung viral replication for at least 20 weeks postimmunization. A single VLP dose elicited F- and M-specific lung TCD8s with higher function and lower expression of PD-1 and other inhibitory receptors than TCD8s from HMPV-infected mice. However, after HMPV challenge, lung TCD8s from VLP-vaccinated mice exhibited inhibitory receptor expression and functional impairment similar to those of mice experiencing secondary infection. HMPV challenge of VLP-immunized μMT mice also elicited a large percentage of impaired lung TCD8s, similar to mice experiencing secondary infection. Together, these results indicate that VLPs are a promising vaccine candidate but do not prevent lung TCD8 impairment upon HMPV challenge. IMPORTANCE Human metapneumovirus (HMPV) is a leading cause of acute respiratory disease for which there is no licensed vaccine. Virus-like particles (VLPs) are an attractive vaccine candidate and induce antibodies, but T cell responses are less defined. Moreover, HMPV and other respiratory viruses induce lung CD8+ T cell (TCD8) impairment mediated by

  18. Study of Demodex mites: Challenges and Solutions.

    PubMed

    Lacey, N; Russell-Hallinan, A; Powell, F C

    2016-05-01

    Demodex mites are the largest and most complex organisms of the skin microflora. How they interact with the innate and adaptive immune systems is unknown. Their potential to have a pathogenic role in the causation of human skin disorders causes continued speculation. With growing interest in the microflora of human skin and its relevance to cutaneous health, the role of Demodex mites needs to be better understood. The main challenges facing scientists investigating the role of these organisms and possible solutions are reviewed under the following headings: (1) Determining the mite population in skin, (2) Transporting, extracting and imaging live mites, (3) Maintaining mites viable ex vivo and (4) Establishing methods to determine the immune response to Demodex mites and their internal contents. PMID:26695086

  19. Chlamydia trachomatis mouse pneumonitis lung infection in IL-18 and IL-12 knockout mice: IL-12 is dominant over IL-18 for protective immunity.

    PubMed Central

    Lu, H.; Yang, X.; Takeda, K.; Zhang, D.; Fan, Y.; Luo, M.; Shen, C.; Wang, S.; Akira, S.; Brunham, R. C.

    2000-01-01

    BACKGROUND: Interferon (IFN)-gamma is a key to protective immunity against a variety of intracellular bacterial infections, including Chlamydia trachomatis. Interleukin (IL)-18, a recently identified Th1 cytokine, together with IL-12 is a strong stimulator for IFN-gamma production. We investigated the relative roles of IL-18 and IL- 12 in protective immunity to C. trachomatis mouse pneumonitis (MoPn) infection using gene knockout (KO) and wild-type (WT) mice. MATERIALS AND METHODS: Mice were intranasally infected with C. trachomatis MoPn and protective immunity was assessed among groups of mice by daily body weight changes, lung growth of MoPn, and histopathological appearances at day 10 postinfection. The corresponding immune responses for each group of mice at the same postinfection time point were evaluated by measuring antigen-specific antibody isotype responses and cytokine profiles. RESULTS: Our results showed that IL-18 deficiency had little or no influence on clearance of MoPn from the lung, although KO mice exhibited slightly more severe inflammatory reactions in lung tissues, as well as reduced systemic and local IFN-gamma production, compared with WT mice. Results with IL-18 KO mice were in sharp contrast to those observed with IL-12 KO mice that showed substantially reduced clearance of MoPn from the lungs, substantial reductions of antigen-specific systemic and lung IFN-gamma production, decreased ratio of MoPn-specific immunoglobulin G (IgG)2a/IgG1, and severe pathological changes in the lung with extensive polymorphonuclear, instead of mononuclear, cell infiltration. Exogenous IL-12 or IL-18 was able to increase IFN-gamma production in IL-18 KO mice; whereas, only exogenous IL-12, but not IL-18, enhanced IFN-gamma production in IL-12 KO mice. Caspase-1 is the key protease for activation of IL-18 precursor into the bioactive form, and caspase-1 KO mice also displayed similar bacterial clearance and body weight loss to that in WT mice at early stages

  20. Exercise effects on IFN-beta expression and viral replication in lung macrophages after HSV-1 infection.

    PubMed

    Kohut, M L; Davis, J M; Jackson, D A; Jani, P; Ghaffar, A; Mayer, E P; Essig, D A

    1998-12-01

    Mice exercised to fatigue and exposed to herpes simplex virus type 1 (HSV-1) exhibit greater mortality than control mice. In this study, we examined lung macrophage resistance to HSV-1 after exercise in terms of both viral replication and interferon (IFN)-beta production. We utilized the reverse transcriptase-rapid polymerase chain reaction to measure the IFN-beta mRNA content in alveolar macrophages. IFN release was measured with a bioassay, and viral replication within the macrophage was assessed by plaque titration. Exercised (Ex) mice ran on a treadmill until fatigue while control (Con) mice remained in lanes above the treadmill. After exercise, alveolar macrophages were removed and incubated with HSV-1. Alveolar macrophage IFN-beta mRNA was greater in Ex than in Con mice. Culture supernatant from infected macrophages showed a higher degree of IFN release and a higher number of infectious viral particles in Ex vs. Con mice. It is likely that the increase in IFN-beta mRNA occurs in response to a higher degree of viral replication. These results suggest that macrophages from Ex mice are less resistant to infection with HSV-1.

  1. Effects of ozone on the defense to a respiratory Listeria monocytogenes infection in the rat. Suppression of macrophage function and cellular immunity and aggravation of histopathology in lung and liver during infection

    SciTech Connect

    Van Loveren, H.; Rombout, P.J.; Wagenaar, S.S.; Walvoort, H.C.; Vos, J.G.

    1988-07-01

    We have investigated the effect of exposure to ozone on defense mechanisms to a respiratory infection with Listeria monocytogenes in the rat. For this purpose rats were continuously exposed to O/sub 3/ concentrations ranging from 0.25 to 2.0 mg/m3 for a period of 1 week. In this model defense to a respiratory infection with Listeria depends on acquired specific cellular immune responses, as well as on natural nonspecific defense mechanisms. The results confirm earlier findings that show that ozone exposure can suppress the capacity of macrophages to ingest and kill Listeria. Moreover, the results show that ozone can also have a suppressive effect on the development of cellular immune responses to a respiratory Listeria infection, i.e., on T/B ratios in lung draining lymph nodes, delayed-type hypersensitivity responses to Listeria antigen, and lymphoproliferative responses in spleen and lung draining lymph nodes to Listeria antigen. The effects on the specific immune responses are especially overt if exposure to the oxidant gas occurs during an ongoing primary infection. The pathological lesions induced by a pulmonary Listeria monocytogenes infection were characterized by multifocal infiltrates of histiocytic and lymphoid cells. The foci sometimes had a granulomatous appearance. Moreover, the cellularity of the interstitial tissues was increased. In the lung many diffuse alveolar macrophages could be seen in the alveoli. Ozone exposure greatly increased the severity of the lung lesions and also of liver lesions resulting from the pulmonary infection. A prominent finding was the formation of granulomas in ozone-exposed and Listeria-infected rats.

  2. Entomopathogenic fungi as potential biocontrol agents of the ecto-parasitic mite, Varroa destructor, and their effect on the immune response of honey bees (Apis mellifera L.).

    PubMed

    Hamiduzzaman, Mollah Md; Sinia, Alice; Guzman-Novoa, Ernesto; Goodwin, Paul H

    2012-11-01

    Three isolates of each of the entomopathogenic fungi, Metarhizium anisopliae, Beauveria bassiana and Clonostachys rosea, were assessed for their pathogenicity to the honey bee parasitic mite, Varroa destructor. The fungi were applied to varroa mites by immersing them in a spore solution, and then the inoculated mites were placed on honey bee brood inside capped cells. At 7 days post inoculation (dpi), the three fungi caused significant varroa mortality compared to non-inoculated mites. In brood treated only with varroa mites, expression of the honey bee genes, hymenoptaecin and poly U binding factor 68 Kd (pUf68), decreased over time, while expression of blue cheese (BlCh) and single minded (SiMd) was not affected. In brood inoculated directly only with M. anisopliae or B. bassiana, the emerged adults showed reduced weight indicating infection by the fungi, which was confirmed by observation of hyphae in the brood. Fungal infection of the brood resulted in increased expression of hymenoptaecin, pUf68 and BlCh, but not SiMd. In brood treated with varroa mites that had been inoculated with the fungi, expression of hymenoptaecin, pUf68 and BlCh, but not SiMd, was even more up-regulated. While varroa mites can suppress gene expression in honey bee brood, varroa mites infected with entomopathogenic fungi induced their expression. This may be due to a low level of fungal infection of the bee, which negated the immunosuppression by the mites. Therefore, entomopathogenic fungi could reduce varroa mite damage to honey bee brood by both infecting the parasite and preventing varroa-associated suppression of honey bee immunity.

  3. NLRC4 inflammasome-mediated production of IL-1β modulates mucosal immunity in the lung against gram-negative bacterial infection.

    PubMed

    Cai, Shanshan; Batra, Sanjay; Wakamatsu, Nobuko; Pacher, Pal; Jeyaseelan, Samithamby

    2012-06-01

    Bacterial flagellin is critical to mediate NLRC4 inflammasome-dependent caspase-1 activation. However, Shigella flexneri, a nonflagellated bacterium, and a flagellin (fliC) knockout strain of Pseudomonas aeruginosa are known to activate NLRC4 in bone marrow-derived macrophages. Furthermore, the flagellin-deficient fliC strain of P. aeruginosa was used in a mouse model of peritonitis to show the requirement of NLRC4. In a model of pulmonary P. aeruginosa infection, flagellin was shown to be essential for the induction of NLRC4-dependent caspase-1 activation. Moreover, in all P. aeruginosa studies, IL-1β production was attenuated in NLRC4(-/-) mice; however, the role of IL-1β in NLRC4-mediated innate immunity in the lungs against a nonflagellated bacterium was not explored. In this article, we report that NLRC4 is important for host survival and bacterial clearance, as well as neutrophil-mediated inflammation in the lungs following Klebsiella pneumoniae infection. NLRC4 is essential for K. pneumoniae-induced production of IL-1β, IL-17A, and neutrophil chemoattractants (keratinocyte cell-derived chemokines, MIP-2, and LPS-induced CXC chemokines) in the lungs. NLRC4 signaling in hematopoietic cells contributes to K. pneumoniae-induced lung inflammation. Furthermore, exogenous IL-1β, but not IL-18 or IL-17A, partially rescued survival, neutrophil accumulation, and cytokine/chemokine expression in the lungs of NLRC4(-/-) mice following infectious challenge. Furthermore, IL-1R1(-/-) mice displayed a decrease in neutrophilic inflammation in the lungs postinfection. Taken together, these findings provide novel insights into the role of NLRC4 in host defense against K. pneumoniae infection.

  4. Mites and internal parasites associated with the common dung beetle Geotrupes (Anoplotrupes) stercorosus (Hartmann in Scriba, 1791) in Poland.

    PubMed

    Sulgostowska, Teresa; Solarz, Krzysztof; Madej, Grażyna; Klimaszewski, Krzysztof

    2015-12-01

    Common dung beetles collected in the "Sobieski Forest" (eastern border of Warsaw suburbs) were examined for the occurrence and prevalence of infections or infestations with intestinal parasites and phoretic mites in relation to soil characteristics and quality of the forest habitat. Endoparasitic fauna was represented by gregarines Didymophyes paradoxa, microsporidians Plistophora geotrupina and cysticerkoids of 2 tapeworms - Ditestolepis diaphana and Staphylocystis furcate. Prevalence of these infections was higher for beetles collected from rich habitats. Acarofauna was represented by hypopodes of Sancassania geotruporum (Astigmatina, Acaridae) and the following taxa of mesostigmatic mites: Alliphis halleri, Macrocheles glaber, Parasitus coleoptratorum and unidentified juvenile Laelapidae representative. Mites were most abundant in June, July and September. They were only slightly more numerously found on dung beetles from the rich habitats. Nonmetric multidimensional scaling, MDS (2D stress = 0.13) revealed significant similarities in the distribution of mite taxa between poor and rich sites and among the investigated months (June, July and September).

  5. Occurrence and seasonal prevalence of the coconut mite, Aceria guerreronis (Eriophyidae), and associated arthropods in Oman.

    PubMed

    Al-Shanfari, Abdulaziz; Hountondji, Fabien C C; Al-Zawamri, Hamid; Rawas, Hassan; Al-Mashiki, Yussef; de Moraes, Gilberto J; Moore, Dave; Gowen, Simon R

    2013-06-01

    The coconut palm is an important crop in the sub arid coastal plain of Dhofar, Oman, for the high demand for its nut water and its use as ornamental plant. Damage of coconut fruits by the eriophyid mite Aceria guerreronis Keifer was first reported in that region in the late 1980s, but background information about the ecology of the pest in Oman was missing. Four surveys were conducted in different seasons from 2008 to 2009, to assess the distribution and prevalence of the coconut mite and its damage as well as the presence of natural enemies. Infestation by the coconut mite was conspicuous on most (99.7 %) palm trees, with 82.5 % damaged fruits. The average (± SE) density of coconut mites per fruit was 750 ± 56; this level of infestation led to the incidence of over 25 % of surface damage on more than half of the fruits. The mite appeared more abundant at the end of the cold season through the summer. No significant differences were observed between infestation levels on local varieties, hybrids and on dwarf varieties. Neoseiulus paspalivorus (De Leon), Cydnoseius negevi (Swirski & Amitai) and Amblyseius largoensis (Muma) were the predatory mites found under the bracts of over 30 % of the coconut fruits and on 68 % of the coconut trees. Considering all sampling dates and all varieties together, average (± SE) phytoseiid density was 1.4 ± 1.19 per fruit. Other mites found in the same habitat as A. guerreronis included the tarsonemids Steneotarsonemus furcatus De Leon and Nasutitarsonemus omani Lofego & Moraes. The pathogenic fungus Hirsutella thompsonii Fisher was rarely found infecting the coconut mite in Dhofar. Other fungal pathogens, namely Cordyceps sp. and Simplicillium sp., were more prevalent.

  6. Occurrence and seasonal prevalence of the coconut mite, Aceria guerreronis (Eriophyidae), and associated arthropods in Oman.

    PubMed

    Al-Shanfari, Abdulaziz; Hountondji, Fabien C C; Al-Zawamri, Hamid; Rawas, Hassan; Al-Mashiki, Yussef; de Moraes, Gilberto J; Moore, Dave; Gowen, Simon R

    2013-06-01

    The coconut palm is an important crop in the sub arid coastal plain of Dhofar, Oman, for the high demand for its nut water and its use as ornamental plant. Damage of coconut fruits by the eriophyid mite Aceria guerreronis Keifer was first reported in that region in the late 1980s, but background information about the ecology of the pest in Oman was missing. Four surveys were conducted in different seasons from 2008 to 2009, to assess the distribution and prevalence of the coconut mite and its damage as well as the presence of natural enemies. Infestation by the coconut mite was conspicuous on most (99.7 %) palm trees, with 82.5 % damaged fruits. The average (± SE) density of coconut mites per fruit was 750 ± 56; this level of infestation led to the incidence of over 25 % of surface damage on more than half of the fruits. The mite appeared more abundant at the end of the cold season through the summer. No significant differences were observed between infestation levels on local varieties, hybrids and on dwarf varieties. Neoseiulus paspalivorus (De Leon), Cydnoseius negevi (Swirski & Amitai) and Amblyseius largoensis (Muma) were the predatory mites found under the bracts of over 30 % of the coconut fruits and on 68 % of the coconut trees. Considering all sampling dates and all varieties together, average (± SE) phytoseiid density was 1.4 ± 1.19 per fruit. Other mites found in the same habitat as A. guerreronis included the tarsonemids Steneotarsonemus furcatus De Leon and Nasutitarsonemus omani Lofego & Moraes. The pathogenic fungus Hirsutella thompsonii Fisher was rarely found infecting the coconut mite in Dhofar. Other fungal pathogens, namely Cordyceps sp. and Simplicillium sp., were more prevalent. PMID:23435864

  7. The Role of Surfactant in Lung Disease and Host Defense against Pulmonary Infections.

    PubMed

    Han, SeungHye; Mallampalli, Rama K

    2015-05-01

    Pulmonary surfactant is essential for life as it lines the alveoli to lower surface tension, thereby preventing atelectasis during breathing. Surfactant is enriched with a relatively unique phospholipid, termed dipalmitoylphosphatidylcholine, and four surfactant-associated proteins, SP-A, SP-B, SP-C, and SP-D. The hydrophobic proteins, SP-B and SP-C, together with dipalmitoylphosphatidylcholine, confer surface tension-lowering properties to the material. The more hydrophilic surfactant components, SP-A and SP-D, participate in pulmonary host defense and modify immune responses. Specifically, SP-A and SP-D bind and partake in the clearance of a variety of bacterial, fungal, and viral pathogens and can dampen antigen-induced immune function of effector cells. Emerging data also show immunosuppressive actions of some surfactant-associated lipids, such as phosphatidylglycerol. Conversely, microbial pathogens in preclinical models impair surfactant synthesis and secretion, and microbial proteinases degrade surfactant-associated proteins. Deficiencies of surfactant components are classically observed in the neonatal respiratory distress syndrome, where surfactant replacement therapies have been the mainstay of treatment. However, functional or compositional deficiencies of surfactant are also observed in a variety of acute and chronic lung disorders. Increased surfactant is seen in pulmonary alveolar proteinosis, a disorder characterized by a functional deficiency of the granulocyte-macrophage colony-stimulating factor receptor or development of granulocyte-macrophage colony-stimulating factor antibodies. Genetic polymorphisms of some surfactant proteins such as SP-C are linked to interstitial pulmonary fibrosis. Here, we briefly review the composition, antimicrobial properties, and relevance of pulmonary surfactant to lung disorders and present its therapeutic implications.

  8. terMITEs: miniature inverted-repeat transposable elements (MITEs) in the termite genome (Blattodea: Termitoidae).

    PubMed

    Luchetti, Andrea

    2015-08-01

    Transposable elements (TEs) are discrete DNA sequences which are able to replicate and jump into different genomic locations. Miniature inverted-repeats TEs (MITEs) are non-autonomous DNA elements whose origin is still poorly understood. Recently, some MITEs were found to contain core repeats that can be arranged in tandem arrays; in some instances, these arrays have even given rise to satellite DNAs in the (peri)centromeric region of the host chromosomes. I report the discovery and analysis of three new MITEs found in the genome of several termite species (hence the name terMITEs) in two different families. For two of the MITEs (terMITE1-Tc1/mariner superfamily; terMITE2-piggyBac superfamily), evidence of past mobility was retrieved. Moreover, these two MITEs contained core repeats, 16 bp and 114 bp long respectively, exhibiting copy number variation. In terMITE2, the tandem duplication appeared associated with element degeneration, in line with a recently proposed evolutionary model on MITEs and the origin of tandem arrays. Concerning their genomic distribution, terMITE1 and terMITE3 appeared more frequently inserted close to coding regions while terMITE2 was mostly associated with TEs. Although MITEs are commonly distributed in coding regions, terMITE2 distribution is in line with that of other insects' piggyBac-related elements and of other small TEs found in termite genomes. This has been explained through insertional preference rather than through selective processes. Data presented here add to the knowledge on the poorly exploited polyneopteran genomes and will provide an interesting framework in which to study TEs' evolution and host's life history traits.

  9. House-dust Mite Asthma. Results of Challenge Tests on Five Criteria with Dermatophagoides pteronyssinus

    PubMed Central

    McAllen, Monica K.; Assem, E. S. K.; Maunsell, K.

    1970-01-01

    Twenty-eight patients with asthma and house-dust allergy were investigated by five different challenge tests with mite extract (Dermatophagoides pteronyssinus). These tests were performed on the skin, bronchi, nasal mucosa, and leucocytes, and on normal human lung tissue passively sensitized by the patients' serum. The results were compared with each other and with the clinical state of the patients. Of 21 patients on whom all five tests were carried out, positive reactions to every test were found in 14 (67%). Asthmatic attacks were readily induced by inhalation of the mite extract and occurred in 18 (86%). Nasal reactions were provoked in 18 (86%) and were not followed by asthmatic symptoms. A leucocyte test was positive in 19 (90%) and the serum test was positive in all (100%). Delayed asthmatic responses to bronchial challenge were seen in six patients, but there was no evidence that these were mediated by precipitins. Quantitatively there was no fixed pattern between the degrees of sensitivity of the different tissues in the same patient. The amount of mite antigen capable of causing an asthmatic reaction was extremely small—less than 1 μg. of mite material in several patients. In view of the prevalence of D. pteronyssinus in this country and its high allergenic potency, it is considered that this mite is an important factor in allergic asthma. PMID:4987898

  10. Diarrhea and acaroid mites: A clinical study

    PubMed Central

    Li, Chao-Pin; Cui, Yu-Bao; Wang, Jian; Yang, Qing-Gui; Tian, Ye

    2003-01-01

    AIM: To explore the characteristics of diarrhea caused by acaroid mites. METHODS: Acaroid mites in fresh stools of 241 patients with diarrhea were separated by flotation in saturated saline. Meanwhile, skin prick test, total IgE and mite-specific IgE were detected in all patients. RESULTS: The total positive rate of mites in stool samples of the patients was 17.01% (41/241), the positive rates of mites in male and female patients were 15.86% (23/145) and 18.75% (18/96), respectively, without significant difference (P > 0.05). The percentage of skin prick test as" +++", "++", "+", and "-" was 9.13% (22/241), 7.47% (18/241), 5.81% (14/241), 4.98% (12/241) and 72.61% (175/241), respectively. The serum levels of total IgE, mite-specific IgE in patients with and without mites in stool samples were (165.72 ± 78.55) IU/ml, (132.44 ± 26.80) IU/mL and (145.22 ± 82.47) IU/ml, (67.35 ± 45.28) IU/ml, respectively, with significant difference (P < 0.01). The positive rate of mites in stool samples in staffs working in traditional Chinese medicine storehouses or rice storehouses (experimental group) was 26.74% (23/86), which was significantly higher than that (11.61%, 18/155) in people engaged in other professions (χ2 = 8.97, P < 0.01). CONCLUSION: Acaroid mites cause diarrhea and increase serum levels of total IgE and mite-specific IgE of patients, and the prevalence of diarrhea caused by acaroid mites is associated with occupations rather than the gender of patients. PMID:12854179

  11. A Hematogenously Disseminated Orientia tsutsugamsushi-Infected Murine Model of Scrub Typhus

    PubMed Central

    Shelite, Thomas R.; Saito, Tais B.; Mendell, Nicole L.; Gong, Bin; Xu, Guang; Soong, Lynn; Valbuena, Gustavo; Bouyer, Donald H.; Walker, David H.

    2014-01-01

    Orientia tsutsugamushi, the etiologic agent of scrub typhus, is a mite-borne rickettsia transmitted by the parasitic larval stage of trombiculid mites. Approximately one-third of the world's population is at risk of infection with Orientia tsutsugamushi, emphasizing its importance in global health. In order to study scrub typhus, Orientia tsutsugamushi Karp strain has been used extensively in mouse studies with various inoculation strategies and little success in inducing disease progression similar to that of human scrub typhus. The objective of this project was to develop a disease model with pathology and target cells similar to those of severe human scrub typhus. This study reports an intravenous infection model of scrub typhus in C57BL/6 mice. This mouse strain was susceptible to intravenous challenge, and lethal infection occurred after intravenous inoculation of 1.25×106 focus (FFU) forming units. Signs of illness in lethally infected mice appeared on day 6 with death occurring ∼6 days later. Immunohistochemical staining for Orientia antigens demonstrated extensive endothelial infection, most notably in the lungs and brain. Histopathological analysis revealed cerebral perivascular, lymphohistiocytic infiltrates, focal hemorrhages, meningoencephalitis, and interstitial pneumonia. Disseminated infection of endothelial cells with Orientia in C57BL/6 mice resulted in pathology resembling that of human scrub typhus. The use of this model will allow detailed characterization of the mechanisms of immunity to and pathogenesis of O. tsutsugamushi infection. PMID:25010338

  12. Disruption of Early Tumor Necrosis Factor Alpha Signaling Prevents Classical Activation of Dendritic Cells in Lung-Associated Lymph Nodes and Development of Protective Immunity against Cryptococcal Infection

    PubMed Central

    Xu, Jintao; Eastman, Alison J.; Flaczyk, Adam; Neal, Lori M.; Zhao, Guolei; Carolan, Jacob; Malachowski, Antoni N.; Stolberg, Valerie R.; Yosri, Mohammed; Chensue, Stephen W.; Curtis, Jeffrey L.; Osterholzer, John J.

    2016-01-01

    ABSTRACT Anti-tumor necrosis factor alpha (anti-TNF-α) therapies have been increasingly used to treat inflammatory diseases and are associated with increased risk of invasive fungal infections, including Cryptococcus neoformans infection. Using a mouse model of cryptococcal infection, we investigated the mechanism by which disruption of early TNF-α signaling results in the development of nonprotective immunity against C. neoformans. We found that transient depletion of TNF-α inhibited pulmonary fungal clearance and enhanced extrapulmonary dissemination of C. neoformans during the adaptive phase of the immune response. Higher fungal burdens in TNF-α-depleted mice were accompanied by markedly impaired Th1 and Th17 responses in the infected lungs. Furthermore, early TNF-α depletion also resulted in disrupted transcriptional initiation of the Th17 polarization program and subsequent upregulation of Th1 genes in CD4+ T cells in the lung-associated lymph nodes (LALN) of C. neoformans-infected mice. These defects in LALN T cell responses were preceded by a dramatic shift from a classical toward an alternative activation of dendritic cells (DC) in the LALN of TNF-α-depleted mice. Taken together, our results indicate that early TNF-α signaling is required for optimal DC activation, and the initial Th17 response followed by Th1 transcriptional prepolarization of T cells in the LALN, which further drives the development of protective immunity against cryptococcal infection in the lungs. Thus, administration of anti-TNF-α may introduce a particularly greater risk for newly acquired fungal infections that require generation of protective Th1/Th17 responses for their containment and clearance. PMID:27406560

  13. MicroRNA expression profiles and networks in mouse lung infected with H1N1 influenza virus.

    PubMed

    Bao, Yanyan; Gao, Yingjie; Jin, Yahong; Cong, Weihong; Pan, Xin; Cui, Xiaolan

    2015-10-01

    Influenza A viruses can cause localized outbreaks and worldwide pandemics, owing to their high transmissibility and wide host range. As such, they are among the major diseases that cause human death. However, the molecular changes induced by influenza A virus infection in lung tissue are not entirely clear. Changes in microRNA (miRNA) expression occur in many pathological and physiological processes, and influenza A virus infection has been shown to alter miRNA expression in cultured cells and animal models. In this study, we mined key miRNAs closely related to influenza A virus infection and explored cellular regulatory mechanisms against influenza A virus infection, by building networks among miRNAs and genes, gene ontologies (GOs), and pathways. In this study, miRNAs and mRNAs induced by H1N1 influenza virus infection were measured by gene chips, and we found that 82 miRNAs and 3371 mRNAs were differentially expressed. The 82 miRNAs were further analyzed with the series test of cluster (STC) analysis. Three of the 16 cluster profiles identified by STC, which include 46 miRNAs in the three profiles, changed significantly. Using potential target genes of the 46 miRNAs, we looked for intersections of these genes with 3371 differentially expressed mRNAs; 719 intersection genes were identified. Based on the GO or KEGG databases, we attained GOs or pathways for all of the above intersection genes. Fisher's and χ (2) test were used to calculate p value and false discovery rate (FDR), and according to the standard of p < 0.001, 241 GOs and 76 pathways were filtered. Based on these data, miRNA-gene, miRNA-GO, and miRNA-pathway networks were built. We then extracted three classes of GOs (related to inflammatory and immune response, cell cycle, proliferation and apoptosis, and signal transduction) to build three subgraphs, and pathways strictly related with H1N1 influenza virus infection were filtered to extract a subgraph of the miRNA-pathway network. Last, according

  14. Control of influenza infection is impaired by diminished interferon-γ secretion by CD4 T cells in the lungs of toddler mice.

    PubMed

    Verhoeven, David; Perry, Sheldon; Pryharski, Karin

    2016-07-01

    Respiratory viral infections, such as influenza, can lead to delayed viral clearance in toddlers, possibly exacerbating disease morbidity. We hypothesized that defective CD4 T cells in toddlers may contribute to a failure to clear virus at a similar rate to adults. Thus, we developed a young mouse model to examine potential divergent responses between toddlers and adults. We determined that young mice (toddler mice, 21 d old) were actively generating and recruiting effector/memory T cells, whereas memory populations were firmly established in older, adult mice (8-10 wk old). We infected toddler and adult mice with influenza A/PR8/34 (H1N1) and found young mice had elevated morbidity, as measured by enhanced weight loss and lower partial pressure of oxygen levels, throughout the infection, thus, modeling the higher morbidity observed in children (<2 y old) during infection. Early viral loads were comparable to adult mice, but toddler mice failed to clear virus by 10 d postinfection. This delayed clearance corresponded to poor lung recruitment of CD4 T cells, lower antiviral T cell responses, and lower B cell/antibodies in the lungs. Mechanistically, diminished interferon-γ was detected in the lungs of toddler mice throughout the infection and corresponded to intrinsic, rather than extrinsic, CD4 T cell limitations in interferon-γ transcription. Moreover, defects in interferon-γ production appeared downstream from signal transducer and activator of transcription 4 in the interleukin-12 signaling pathway, suggesting maturational delays different from neonates. Importantly, recombinant interferon-γ supplementation rescued CD4 T cell numbers in the lungs and influenza-specific antibody formation. This study highlights the intrinsic limitations in CD4 T cell effector functions that may arise in toddlers and contribute to disease pathology. PMID:26823488

  15. Heterogeneous pathological outcomes after experimental pH1N1 influenza infection in ferrets correlate with viral replication and host immune responses in the lung.

    PubMed

    Vidaña, Beatriz; Martínez, Jorge; Martínez-Orellana, Pamela; García Migura, Lourdes; Montoya, María; Martorell, Jaime; Majó, Natàlia

    2014-01-01

    The swine-origin pandemic (p) H1N1 influenza A virus causes mild upper-respiratory tract disease in most human patients. However, some patients developed severe lower-respiratory tract infections with fatal consequences, and the cause of these infections remain unknown. Recently, it has been suggested that different populations have different degrees of susceptibility to pH1N1 strains due to host genetic variations that are associated with inappropriate immune responses against viral genetic characteristics. Here, we tested whether the pathologic patterns of influenza strains that produce different disease outcomes in humans could be reproduced in a ferret model. Our results revealed that the severities of infection did not correspond to particular viral isolate and were not associated with the clinical phenotypes of the corresponding patients. Severe pathological outcomes were associated with higher viral replication, especially in alveolar areas, and with an exacerbated innate cellular immune response that was characterised by substantial phagocytic and cytotoxic cell migration into the lungs. Moreover, detrimental innate cellular responses were linked to the up-regulation of several proinflammatory cytokines and chemokines and the down-regulation of IFNα in the lungs. Additionally, severe lung lesions were associated with greater up-regulations of pro-apoptotic markers and higher levels of apoptotic neutrophils and macrophages. In conclusion, this study confirmed that the clinicopathological outcomes of pH1N1 infection in ferrets were not only due to viral replication abilities but also depended on the hosts' capacities to mount efficient immune responses to control viral infection of the lung.

  16. The poultry red mite, Dermanyssus gallinae, a potential vector of Erysipelothrix rhusiopathiae causing erysipelas in hens.

    PubMed

    Chirico, J; Eriksson, H; Fossum, O; Jansson, D

    2003-06-01

    Erysipelas is a bacterial disease caused by Erysipelothrix rhusiopathiae, which may infect swine as well as several other species of mammals and birds, including domestic fowl. In poultry, erysipelas may cause sudden high mortality due to septicemia. This communication describes the first isolation of E. rhusiopathiae from the haematophagous poultry red mite, Dermanyssus gallinae DeGeer (Acari: Dermanyssidae), that was collected on three farms where hen erysipelas was diagnosed. The bacteria were isolated from the integument as well as from the interior of the mites. Serotypes 1a and 1b of E. rhusiopathiae found in the mites corresponded with those isolated from the diseased birds. These findings imply that D. gallinae is a potential vector of E. rhusiopathiae. The current lack of effective measures to control D. gallinae causes recurring mite problems in poultry facilities once afflicted by this parasite. Consequently, mites containing E. rhusiopathiae may act as reservoir hosts of this bacterium, allowing it to persist in the poultry house between flock cycles as a source of infection for the replacement pullets. The zoonotic potentials of both E. rhusiopathiae and D. gallinae should also be considered.

  17. Lung transplantation

    PubMed Central

    Afonso, José Eduardo; Werebe, Eduardo de Campos; Carraro, Rafael Medeiros; Teixeira, Ricardo Henrique de Oliveira Braga; Fernandes, Lucas Matos; Abdalla, Luis Gustavo; Samano, Marcos Naoyuki; Pêgo-Fernandes, Paulo Manuel

    2015-01-01

    ABSTRACT Lung transplantation is a globally accepted treatment for some advanced lung diseases, giving the recipients longer survival and better quality of life. Since the first transplant successfully performed in 1983, more than 40 thousand transplants have been performed worldwide. Of these, about seven hundred were in Brazil. However, survival of the transplant is less than desired, with a high mortality rate related to primary graft dysfunction, infection, and chronic graft dysfunction, particularly in the form of bronchiolitis obliterans syndrome. New technologies have been developed to improve the various stages of lung transplant. To increase the supply of lungs, ex vivo lung reconditioning has been used in some countries, including Brazil. For advanced life support in the perioperative period, extracorporeal membrane oxygenation and hemodynamic support equipment have been used as a bridge to transplant in critically ill patients on the waiting list, and to keep patients alive until resolution of the primary dysfunction after graft transplant. There are patients requiring lung transplant in Brazil who do not even come to the point of being referred to a transplant center because there are only seven such centers active in the country. It is urgent to create new centers capable of performing lung transplantation to provide patients with some advanced forms of lung disease a chance to live longer and with better quality of life. PMID:26154550

  18. Detection of Quiescent Infections with Multiple Elephant Endotheliotropic Herpesviruses (EEHVs), Including EEHV2, EEHV3, EEHV6, and EEHV7, within Lymphoid Lung Nodules or Lung and Spleen Tissue Samples from Five Asymptomatic Adult African Elephants

    PubMed Central

    Zong, Jian-Chao; Heaggans, Sarah Y.; Long, Simon Y.; Latimer, Erin M.; Nofs, Sally A.; Bronson, Ellen; Casares, Miguel; Fouraker, Michael D.; Pearson, Virginia R.; Richman, Laura K.

    2015-01-01

    ABSTRACT More than 80 cases of lethal hemorrhagic disease associated with elephant endotheliotropic herpesviruses (EEHVs) have been identified in young Asian elephants worldwide. Diagnostic PCR tests detected six types of EEHV in blood of elephants with acute disease, although EEHV1A is the predominant pathogenic type. Previously, the presence of herpesvirus virions within benign lung and skin nodules from healthy African elephants led to suggestions that African elephants may be the source of EEHV disease in Asian elephants. Here, we used direct PCR-based DNA sequencing to detect EEHV genomes in necropsy tissue from five healthy adult African elephants. Two large lung nodules collected from culled wild South African elephants contained high levels of either EEHV3 alone or both EEHV2 and EEHV3. Similarly, a euthanized U.S. elephant proved to harbor multiple EEHV types distributed nonuniformly across four small lung nodules, including high levels of EEHV6, lower levels of EEHV3 and EEHV2, and a new GC-rich branch type, EEHV7. Several of the same EEHV types were also detected in random lung and spleen samples from two other elephants. Sanger PCR DNA sequence data comprising 100 kb were obtained from a total of 15 different strains identified, with (except for a few hypervariable genes) the EEHV2, EEHV3, and EEHV6 strains all being closely related to known genotypes from cases of acute disease, whereas the seven loci (4.0 kb) obtained from EEHV7 averaged 18% divergence from their nearest relative, EEHV3. Overall, we conclude that these four EEHV species, but probably not EEHV1, occur commonly as quiescent infections in African elephants. IMPORTANCE Acute hemorrhagic disease characterized by high-level viremia due to infection by members of the Proboscivirus genus threatens the future breeding success of endangered Asian elephants worldwide. Although the genomes of six EEHV types from acute cases have been partially or fully characterized, lethal disease predominantly

  19. Large Porous Particles for Sustained Release of a Decoy Oligonucelotide and Poly(ethylenimine): Potential for Combined Therapy of Chronic Pseudomonas aeruginosa Lung Infections.

    PubMed

    d'Angelo, Ivana; Perfetto, Brunella; Costabile, Gabriella; Ambrosini, Veronica; Caputo, Pina; Miro, Agnese; d'Emmanuele di Villa Bianca, Roberta; Sorrentino, Raffaella; Donnarumma, Giovanna; Quaglia, Fabiana; Ungaro, Francesca

    2016-05-01

    We have recently demonstrated that the specific inhibition of nuclear factor-κB by a decoy oligonucleotide (dec-ODN) delivered through inhalable large porous particles (LPP) made of poly(lactic-co-glycolic acid) (PLGA) may be highly beneficial for long-term treatment of lung inflammation. Nevertheless, besides chronic inflammation, multifunctional systems aimed to control also infection are required in chronic lung diseases, such as cystic fibrosis (CF). In this work, we tested the hypothesis that engineering PLGA-based LPP with branched poly(ethylenimine) (PEI) may improve LPP properties for pulmonary delivery of dec-ODN, with particular regard to the treatment of Pseudomonas aeruginosa lung infections. After getting insight into the role of PEI on the technological properties of PLGA-based LPP for delivery of dec-ODN, the putative synergistic effect of PEI free or PEI released from LPP on in vitro antimicrobial activity of tobramycin (Tb) and aztreonam (AZT) against P. aeruginosa was elucidated. Meanwhile, cytotoxicity studies on A549 cells were carried out. Results clearly demonstrate that the dry powders have promising aerosolization properties and afford a prolonged in vitro release of both dec-ODN and PEI. The encapsulation of PEI into LPP results in a 2-fold reduction of the minimum inhibitory concentration of AZT, while reducing the cytotoxic effect of PEI. Of note, the developed ODN/PLGA/PEI LPP persisted at lung at least for 14 days after intratracheal administration in rats where they can provide sustained and combined release of dec-ODN and PEI. dec-ODN will likely act as an anti-inflammatory drug, while PEI may enhance the therapeutic activity of inhaled antibiotics, which are commonly employed for the treatment of concomitant lung infections. PMID:27002689

  20. Pharmacodynamic Profile of GSK2140944 against Methicillin-Resistant Staphylococcus aureus in a Murine Lung Infection Model

    PubMed Central

    So, Wonhee; Crandon, Jared L.

    2015-01-01

    GSK2140944 is a novel bacterial type II topoisomerase inhibitor with in vitro activity against key causative respiratory pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). We described the pharmacodynamics of GSK2140944 against MRSA in the neutropenic murine lung infection model. MICs of GSK2140944 were determined by broth microdilution. Plasma and epithelial lining fluid (ELF) pharmacokinetics were evaluated to allow determination of pulmonary distribution. Six MRSA isolates were tested. GSK2140944 doses of 1.56 to 400 mg/kg of body weight every 6 h (q6h) were utilized. Efficacy as the change in log10 CFU at 24 h compared with 0 h controls and the area under the concentration-time curve for the free, unbound fraction of a drug (fAUC)/MIC required for various efficacy endpoints were determined. GSK2140944 MICs were 0.125 to 0.5 mg/liter against the six MRSA isolates. ELF penetration ratios ranged from 1.1 to 1.4. Observed maximal decreases were 1.1 to 3.1 log10 CFU in neutropenic mice. The mean fAUC/MIC ratios required for stasis and 1-log-unit decreases were 59.3 ± 34.6 and 148.4 ± 83.3, respectively. GSK2140944 displayed in vitro and in vivo activity against MRSA. The pharmacodynamic profile of GSK2140944, as determined, supports its further development as a potential treatment option for pulmonary infections, including those caused by MRSA. PMID:26055376

  1. The transmission of deformed wing virus between honeybees (Apis mellifera L.) by the ectoparasitic mite varroa jacobsoni Oud

    PubMed

    Bowen-Walker; Martin; Gunn

    1999-01-01

    Under field conditions, Varroa jacobsoni were shown to be highly effective vectors of deformed wing virus (DWV) between bees. Adult female mites obtained from honeybee pupae naturally infected with DWV contained virus titers many times in excess of those found in their hosts and, beyond that, which might be expected from a concentration effect. It is therefore possible that DWV may be capable of replicating within V. jacobsoni. Bees which tested positive for DWV exhibited characteristic morphological deformity and/or they died during pupation. Asymptomatic bees had much lower virus titers than those which were deformed or had died during pupation. It is therefore suggested that for DWV to cause pathology it must be present in pupae above a certain concentration. The amount of DWV vectored by V. jacobsoni will depend on the mites' level of infection, which will in turn depend on whether they had fed previously on dead or deformed bees and also on the rate of replication of the virus within the mites. Consequently, developing bees infested with large numbers of mites could suffer a high incidence of deformity if the mites are heavily infected or harbor an especially virulent strain of virus. A positive relationship was found between increasing numbers of mites on individual bees and the incidence of morphological deformity and death. This probably reflected the large number of viral particles transmitted by the mites, which resulted in many multiply infested bees dying before emergence. These results demonstrate the importance of the role of viruses when considering the pathology of V. jacobsoni and that much of the pathology previously associated with the effects of mite feeding could be attributed directly to secondary pathogens vectored by V. jacobsoni. Copyright 1999 Academic Press. PMID:9878295

  2. The transmission of deformed wing virus between honeybees (Apis mellifera L.) by the ectoparasitic mite varroa jacobsoni Oud

    PubMed

    Bowen-Walker; Martin; Gunn

    1999-01-01

    Under field conditions, Varroa jacobsoni were shown to be highly effective vectors of deformed wing virus (DWV) between bees. Adult female mites obtained from honeybee pupae naturally infected with DWV contained virus titers many times in excess of those found in their hosts and, beyond that, which might be expected from a concentration effect. It is therefore possible that DWV may be capable of replicating within V. jacobsoni. Bees which tested positive for DWV exhibited characteristic morphological deformity and/or they died during pupation. Asymptomatic bees had much lower virus titers than those which were deformed or had died during pupation. It is therefore suggested that for DWV to cause pathology it must be present in pupae above a certain concentration. The amount of DWV vectored by V. jacobsoni will depend on the mites' level of infection, which will in turn depend on whether they had fed previously on dead or deformed bees and also on the rate of replication of the virus within the mites. Consequently, developing bees infested with large numbers of mites could suffer a high incidence of deformity if the mites are heavily infected or harbor an especially virulent strain of virus. A positive relationship was found between increasing numbers of mites on individual bees and the incidence of morphological deformity and death. This probably reflected the large number of viral particles transmitted by the mites, which resulted in many multiply infested bees dying before emergence. These results demonstrate the importance of the role of viruses when considering the pathology of V. jacobsoni and that much of the pathology previously associated with the effects of mite feeding could be attributed directly to secondary pathogens vectored by V. jacobsoni. Copyright 1999 Academic Press.

  3. The lung microbiome after lung transplantation.

    PubMed

    Becker, Julia; Poroyko, Valeriy; Bhorade, Sangeeta

    2014-04-01

    Lung transplantation survival remains significantly impacted by infections and the development of chronic rejection manifesting as bronchiolitis obliterans syndrome (BOS). Traditional microbiologic data has provided insight into the role of infections in BOS. Now, new non-culture-based techniques have been developed to characterize the entire population of microbes resident on the surfaces of the body, also known as the human microbiome. Early studies have identified that lung transplant patients have a different lung microbiome and have demonstrated the important finding that the transplant lung microbiome changes over time. Furthermore, both unique bacterial populations and longitudinal changes in the lung microbiome have now been suggested to play a role in the development of BOS. In the future, this technology will need to be combined with functional assays and assessment of the immune responses in the lung to help further explain the microbiome's role in the failing lung allograft.

  4. Ecto-5'-nucleotidase CD73 modulates the innate immune response to influenza infection but is not required for development of influenza-induced acute lung injury.

    PubMed

    Aeffner, Famke; Woods, Parker S; Davis, Ian C

    2015-12-01

    Extracellular nucleotides and nucleosides are important signaling molecules in the lung. Nucleotide and nucleoside concentrations in alveolar lining fluid are controlled by a complex network of surface ectonucleotidases. Previously, we demonstrated that influenza A/WSN/33 (H1N1) virus resulted in increased levels of the nucleotide ATP and the nucleoside adenosine in bronchoalveolar lavage fluid (BALF) of wild-type (WT) C57BL/6 mice. Influenza-induced acute lung injury (ALI) was highly attenuated in A1-adenosine receptor-knockout mice. Because AMP hydrolysis by the ecto-5'-nucleotidase (CD73) plays a central role in and is rate-limiting for generation of adenosine in the normal lung, we hypothesized that ALI would be attenuated in C57BL/6-congenic CD73-knockout (CD73-KO) mice. Infection-induced hypoxemia, bradycardia, viral replication, and bronchoconstriction were moderately increased in CD73-KO mice relative to WT controls. However, postinfection weight loss, pulmonary edema, and parenchymal dysfunction were not altered. Treatment of WT mice with the CD73 inhibitor 5'-(α,β-methylene) diphosphate (APCP) also had no effect on infection-induced pulmonary edema but modestly attenuated hypoxemia. BALF from CD73-KO and APCP-treated WT mice contained more IL-6 and CXCL-10/IFN-γ-induced protein 10, less CXCL-1/keratinocyte chemoattractant, and fewer neutrophils than BALF from untreated WT controls. BALF from APCP-treated WT mice also contained fewer alveolar macrophages and more transforming growth factor-β than BALF from untreated WT mice. These results indicate that CD73 is not necessary for development of ALI following influenza A virus infection and suggest that tissue-nonspecific alkaline phosphatase may be responsible for increased adenosine generation in the infected lung. However, they do suggest that CD73 has a previously unrecognized immunomodulatory role in influenza. PMID:26432867

  5. IL-17RA in Non-Hematopoietic Cells Controls CXCL-1 and 5 Critical to Recruit Neutrophils to the Lung of Mycobacteria-Infected Mice during the Adaptive Immune Response.

    PubMed

    Lombard, Robin; Doz, Emilie; Carreras, Florence; Epardaud, Mathieu; Le Vern, Yves; Buzoni-Gatel, Dominique; Winter, Nathalie

    2016-01-01

    During chronic infection with Mycobacterium tuberculosis (Mtb), bacilli multiplication is constrained within lung granulomas until excessive inflammation destroys the lung. Neutrophils are recruited early and participate in granuloma formation, but excessive neutrophilia exacerbates the tuberculosis disease. Neutrophils thus appear as potential targets for therapeutic interventions, especially in patients for whom no antibiotic treatment is possible. Signals that regulate neutrophil recruitment to the lung during mycobacterial infection need to be better understood. We demonstrated here, in the mouse model, that neutrophils were recruited to the lung in two waves after intranasal infection with virulent Mtb or the live attenuated vaccine strain Bacillus Calmette Guérin (BCG). A first wave of neutrophils was swiftly recruited, followed by a subsequent adaptive wave that reached the lung together with IFN-γ- and IL-17A-producing T cells. Interestingly, the second neutrophil wave did not participate to mycobacteria control in the lung and established contacts with T cells. The adaptive wave was critically dependent on the expression of IL-17RA, the receptor for IL-17A, expressed in non-hematopoietic cells. In absence of this receptor, curtailed CXCL-1 and 5 production in the lung restrained neutrophil recruitment. CXCL-1 and 5 instillation reconstituted lung neutrophil recruitment in BCG-infected IL17RA-/- mice. PMID:26871571

  6. Cross-reactivity between storage and dust mites and between mites and shrimp.

    PubMed

    Arlian, Larry G; Morgan, Marjorie S; Vyszenski-Moher, DiAnn L; Sharra, Denada

    2009-02-01

    Many patients have sensitivities to multiple species of storage and house dust mites. It is not clear if this is because patients have multiple sensitivities to species-specific mite allergens or if these mites share many cross-reacting allergens. Our objective was to further define the cross-allergenicity between several species of storage and house dust mites using crossed-immunoelectrophoresis (CIE), crossed-radioimmunoelectrophoresis (CRIE), immunoblotting, and ELISA. CIE and CRIE reactions revealed that storage mites shared two cross-antigenic molecules and one of these bound IgE in a serum pool from mite allergic patients. Antibody in anti-sera built to each species of mite recognized many SDS-PAGE resolved proteins of other mite species and this suggested the potential for other cross-reactive allergens. Among patient sera, IgE bound to many different proteins but few had IgE that bound to a protein with common molecular weights across the mite species and this suggested mostly species-specific allergens. Antiserum built to each mite species precipitated one protein in shrimp extracts that bound anti-Der p 10 (tropomyosin) and IgE in the serum pool. Anti-Der p 10 showed strong binding to shrimp tropomyosin but very little to any of the mite proteins. ELISA showed the mite extracts contained very little tropomyosin. The storage and dust mites investigated contain mostly species-specific allergens and very small amounts of the pan-allergen tropomyosin compared to shrimp and snail. PMID:18850281

  7. A mite species that consists entirely of haploid females.

    PubMed

    Weeks, A R; Marec, F; Breeuwer, J A

    2001-06-29

    The dominance of the diploid state in higher organisms, with haploidy generally confined to the gametic phase, has led to the perception that diploidy is favored by selection. This view is highlighted by the fact that no known female organism within the Metazoa exists exclusively (or even for a prolonged period) in a haploid state. We used fluorescence microscopy and variation at nine microsatellite loci to show that the false spider mite, Brevipalpus phoenicis, consists of haploid female parthenogens. We show that this reproductive anomaly is caused by infection by an undescribed endosymbiotic bacterium, which results in feminization of haploid genetic males. PMID:11431565

  8. Human Dermatitis Caused by Ophionyssus natricis, a Snake Mite.

    PubMed

    Amanatfard, Emad; Youssefi, Mohammad Reza; Barimani, Alireza

    2014-01-01

    Ophionyssus natricis is a purely blood sucking parasite of snakes and of worldwide distribution. Infected snakes often exhibit lethargy, pruritus, crusting dermatitis, and behavioral changes. Ophionyssus natricis can also attack humans, causing popular vesiculo-bullous eruption of the skin. A 29 years old man working in zoo, Sari, Mazandaran, Iran, presented itchy papullar eruption of the skin. He had noticed small insects fixed on his skin and large numbers of these same insects on a python and its cage in the zoo. Regarding totheir morphological characteristics they were diagnosed as O. natricis (Geravis, 1844), a snake mite. It is the first report of O. natricis from Iran. PMID:25759743

  9. Black currant reversion virus, a mite-transmitted nepovirus.

    PubMed

    Susi, Petri

    2004-05-01

    SUMMARY Taxonomy: Black currant reversion virus (BRV) is the first identified mite-transmitted member of the genus Nepovirus (family Comoviridae). A few systematic studies have been performed to compare virus isolates from different geographical locations. Physical properties: Purified preparations contain two closely sedimenting centrifugal components (B and M for RNA1 and RNA2, respectively) at varying ratios, and occasionally a T component (for satellite RNA). The BRV capsids have a diameter of 27 nm and they are putatively composed of 60 copies of a single species of capsid (coat) protein assembled in an icosahedral lattice. Diluted plant sap loses its infectivity within 1 day at 20 degrees C and in 4-8 days at 4 degrees C. Hosts: The natural host range of BRV is limited; it infects black currant (Ribes nigrum L.) and some related Ribes species. The transmission of the virus is by the eriophyid gall mite of black currant (Cecidophyopsis ribis). A number of herbaceous plants can be infected experimentally. BRV is the agent of black currant reversion disease (BRD), which is economically the most significant virus disease in Ribes species. BRV and BRD occur widely in locations where black currant is cultivated commercially.

  10. Cophylogeny of quill mites from the genus Syringophilopsis (Acari: Syringophilidae) and their North American passerine hosts.

    PubMed

    Hendricks, Sarah A; Flannery, Maureen E; Spicer, Greg S

    2013-10-01

    Species of Syringophilopsis quill mites are found in the flight feathers of passerine birds. A phylogeny of species from this genus infecting North American passerines was inferred from the mitochondrial cytochrome oxidase I gene and the nuclear 28S ribosomal RNA gene. Based on the large genetic distance among lineages, the genus appears to be composed of several cryptic species. A reconciliation analysis of these mites and their avian hosts indicates a limited, but significant, degree of cophylogeny. However, strict cospeciation is not found to be occurring in this system.

  11. A rare finding of mites (Arachnida: Acari: Leeuwenhoekiidae) parasitising a whip spider (Arachnida: Amblypygi: Charinidae).

    PubMed

    Gonçalves-Souza, Thiago; Giupponi, Alessandro P L; Hernandes, Fabio A

    2014-04-01

    Twelve larvae of unidentified species of Odontacarus Ewing, 1929 (Acari: Leeuwenhoekiidae) were found parasitising an adult male whip spider Charinus brasilianus Weygoldt (Charinidae) in Santa Teresa, mountainous region of Espirito Santo state, southeastern Brazil. These larvae occurred in the intersegmental membrane of prosoma and legs. This is the first report of ectoparasitic mites infecting a charinid whip spider and the first record of leeuwenhoekiid mites parasitising an invertebrate host. We suggest that future studies are essential to understand the reasons why these events of parasitism are so rare in the order Amblypygi.

  12. Seasonal dynamics and distribution of house dust mites in China.

    PubMed

    Feng, Meng; Sun, Wenwen; Cheng, Xunjia

    2009-12-01

    House dust mites are widely distributed in the human habitat and work environment and produce very powerful allergens. The most important allergy-causing mites found in homes worldwide are the house dust mites Dermatophagoides farinae and D. pteronyssinus and the storage mite Blomia tropicalis. It is important to know which mite species are present in a geographical area when performing diagnostic testing and prescribing immunotherapy. We classified the breeding situations of house dust mites in dwellings in northern China. Mites are detectable in March and their number increases from April or May, reaching a peak from July to September. The seasonal distribution of different acaroid mite species may differ: temperature, humidity, and eating habits were the major limiting factors determining species composition and diversity of acaroid mite communities in house ecosystems; comparing to the field and the forest, in human living area including house and working place, acaroid mites showed less bio-diversity.

  13. Haematophagus Mites in Poultry Farms of Iran

    PubMed Central

    Rahbari, S; Nabian, S; Ronaghi, H

    2009-01-01

    Background: Blood sucking mites are important avian ectoparasites which being found on bird species worldwide. Their presence are problematic for the producers either through potential direct effects on weight gain, egg production, sperm production in roosters or as nuisance pests on worker handle hens and eggs. The aim of this study was pointing out of the status of haematophagus mites. Methods: Eight caged layer and four breeder flocks were visited, monitoring for the presence of chicken mites performed by removing and examining debris from poultry house, infested nesting material collected into zip lock plastic bags and at least 20 birds were also randomly selected to examine the presence of chicken mites. Mites obtained from each population were mounted in Hoyer’s medium on microscope slides and identified. All eight caged layer and four breeder flocks were inspected, which were infested with chicken blood feeding mites. Results: Massive infestations of Dermanyssus gallinae were common with huge numbers of parasites on birds, cages and the conveyor belts for egg. Only one farm from Mazandaran Province was infested to Ornithonyssus bursa. Conclusion: Dermanyssus gallinae was the most prevalent blood feeder mite in the breeder and caged layer flocks in Iran, while O. bursa was reported as a first record, which found only in a breeder flock in Mazanderan Province. It seems that its presence is limited into the area which affected by both warm and humid environmental conditions. PMID:22808378

  14. Cryptococcus neoformans Infection in Mice Lacking Type I Interferon Signaling Leads to Increased Fungal Clearance and IL-4-Dependent Mucin Production in the Lungs

    PubMed Central

    Sato, Ko; Yamamoto, Hideki; Nomura, Toshiki; Matsumoto, Ikumi; Miyasaka, Tomomitsu; Zong, Tong; Kanno, Emi; Uno, Kazuko; Ishii, Keiko; Kawakami, Kazuyoshi

    2015-01-01

    Type I interferons (IFNs) are secreted by many cell types upon stimulation via pattern recognition receptors and bind to IFN-α/β receptor (IFNAR), which is composed of IFNAR1 and IFNAR2. Although type I IFNs are well known as anti-viral cytokines, limited information is available on their role during fungal infection. In the present study, we addressed this issue by examining the effect of IFNAR1 defects on the host defense response to Cryptococcus neoformans. In IFNAR1KO mice, the number of live colonies was lower and the host immune response mediated not only by Th1 but also by Th2 and Th17-related cytokines was more accelerated in the infected lungs than in WT mice. In addition, mucin production by bronchoepithelial cells and expression of MUC5AC, a major core protein of mucin in the lungs, were significantly higher in IFNAR1KO mice than in WT mice. This increase in mucin and MUC5AC production was significantly inhibited by treatment with neutralizing anti-IL-4 mAb. In contrast, administration of recombinant IFN-αA/D significantly suppressed the production of IL-4, but not of IFN-γ and IL-17A, in the lungs of WT mice after cryptococcal infection. These results indicate that defects of IFNAR1 led to improved clearance of infection with C. neoformans and enhanced synthesis of IFN-γ and the IL-4-dependent production of mucin. They also suggest that type I IFNs may be involved in the negative regulation of early host defense to this infection. PMID:26384031

  15. Change in abundance of three phytophagous mite species (Acari: Eriophyidae, Tetranychidae) on quackgrass in the presence of choke disease.

    PubMed

    Rector, Brian G; Czarnoleski, Marcin; Skoracka, Anna; Lembicz, Marlena

    2016-09-01

    Phytophagous mites and endophytic fungi may interact when sharing a host plant, potentially influencing one another's growth or population dynamics; however, interactions between them are poorly known and remain largely unexplored. In this study, quantitative associations between three species of phytophagous mites and the endophytic fungus Epichloë bromicola Leuchtm. & Schardl (Clavicipitaceae, Ascomycotina) on quackgrass, Elymus repens (L.) Gould are reported. The mites' abundance was assessed on field-collected grass shoots that were either exhibiting choke disease symptoms or without the fungus. Overall, the abundance of Tetranychus urticae and Aculodes mckenziei was significantly lower on quackgrass plants infected by E. bromicola compared to plants without the fungus. Conversely, populations of Abacarus hystrix were significantly larger on plants colonised by the fungus than on uninfected plants. Thus, the presence of this endophytic fungus may have divergent effects on different phytophagous mite species although the basis of these effects is not yet known. PMID:27388448

  16. Change in abundance of three phytophagous mite species (Acari: Eriophyidae, Tetranychidae) on quackgrass in the presence of choke disease.

    PubMed

    Rector, Brian G; Czarnoleski, Marcin; Skoracka, Anna; Lembicz, Marlena

    2016-09-01

    Phytophagous mites and endophytic fungi may interact when sharing a host plant, potentially influencing one another's growth or population dynamics; however, interactions between them are poorly known and remain largely unexplored. In this study, quantitative associations between three species of phytophagous mites and the endophytic fungus Epichloë bromicola Leuchtm. & Schardl (Clavicipitaceae, Ascomycotina) on quackgrass, Elymus repens (L.) Gould are reported. The mites' abundance was assessed on field-collected grass shoots that were either exhibiting choke disease symptoms or without the fungus. Overall, the abundance of Tetranychus urticae and Aculodes mckenziei was significantly lower on quackgrass plants infected by E. bromicola compared to plants without the fungus. Conversely, populations of Abacarus hystrix were significantly larger on plants colonised by the fungus than on uninfected plants. Thus, the presence of this endophytic fungus may have divergent effects on different phytophagous mite species although the basis of these effects is not yet known.

  17. Evaluation of predation of the mite Lasioseius penicilliger (Aracnida: Mesostigmata) on Haemonchus contortus and bacteria-feeding nematodes.

    PubMed

    Aguilar-Marcelino, L; Quintero-Martínez, M T; Mendoza de Gives, P; López-Arellano, M E; Liébano-Hernández, E; Torres-Hernández, G; González-Camacho, J M; Cid del Prado, I

    2014-03-01

    Predation by the mite Lasioseius penicilliger was studied on three nematode species, i.e. infective larval stages (L3) of Haemonchus contortus and adults of Panagrellus redivivus and Rhabditis sp. Experiments were carried out in 5.5-cm diameter Petri dishes containing 2% water-agar over a period of 5 days. Batches of up to 1500 third-stage larvae (L3) of H. contortus and 1000 adult nematodes of P. redivivus and Rhabditis sp. were exposed to five mites in separate Petri dishes. Upon contact, each mite used its pedipalp and legs to identify and hold its prey and then used its chelicerae to feed upon the prey. Predation by L. penicilliger was chance dependent but mites became aggregated around any injured/damaged prey, thereby suggesting some form of chemoperception. The rate of predation on the three species of nematodes was high but L3 of H. contortus and adult Rhabditis sp. were preferred.

  18. An opilioacarid mite in Cretaceous Burmese amber

    NASA Astrophysics Data System (ADS)

    Dunlop, Jason A.; de Oliveira Bernardi, Leopoldo Ferreira

    2014-09-01

    A fossil opilioacarid mite (Parasitiformes: Opilioacarida) in Burmese amber is described as ? Opilioacarus groehni sp. nov. This ca. 99 Ma record (Upper Cretaceous: Cenomanian) represents only the third fossil example of this putatively basal mite lineage, the others originating from Eocene Baltic amber (ca. 44-49 Ma). Our new record is not only the oldest record of Opilioacarida, but it is also one of the oldest examples of the entire Parasitiformes clade. The presence of Opilioacarida—potentially Opiloacarus—in the Cretaceous of SE Asia suggests that some modern genus groups were formerly more widely distributed across the northern hemisphere, raising questions about previously suggested Gondwanan origins for these mites.

  19. Recombinant Human Respiratory Syncytial Virus (RSV) Monoclonal Antibody Fab is Effective Therapeutically when Introduced Directly into the Lungs of RSV-Infected Mice

    NASA Astrophysics Data System (ADS)

    Crowe, James E., Jr.; Murphy, Brian R.; Chanock, Robert M.; Williamson, R. Anthony; Barbas, Carlos F., III; Burton, Dennis R.

    1994-02-01

    Previously, recombinant human respiratory syncytial virus (RSV) monoclonal antibody Fabs were generated by antigen selection from random combinatorial libraries displayed at the tip of filamentous phage. Two such Fabs, which exhibited high binding affinity for RSV F glycoprotein (a major protective antigen), were evaluated for therapeutic efficacy in infected mice just before or at the time of peak virus replication in the lungs. Fab 19, which neutralized RSV infectivity with high efficiency in tissue culture, was effective therapeutically when delivered directly into the lungs by intranasal instillation under anesthesia. In contrast, RSV Fab 126, which failed to neutralize virus in cell culture, did not exhibit a therapeutic effect under these conditions. The amount of Fab 19 required to effect a 5000- to 12,000-fold reduction in titer of RSV in the lungs within 24 hr was rather small. In four separate experiments, a single instillation of 12.9-50 μg of RSV Fab 19 was sufficient to achieve such a reduction in pulmonary virus in a 25g mouse. The use of Fabs instead of the whole immunoglobulin molecules from which they are derived reduced the protein content of a therapeutic dose. This is important because the protein load that can be delivered effectively into the lungs is limited. The therapeutic effect of a single treatment with Fab 19 was not sustained, so that a rebound in pulmonary virus titer occurred on the 2nd day after treatment. This rebound in pulmonary RSV titer could be prevented by treating infected mice with a single dose of Fab 19 daily for 3 days. These observations suggest that human monoclonal Fabs grown in Escherichia coli may prove useful in the treatment of serious RSV disease as well as diseases caused by other viruses where replication in vivo is limited primarily to the lumenal lining of the respiratory tract.

  20. Efficacy of two fungus-based biopesticide against the honeybee ectoparasitic mite, Varroa destructor.

    PubMed

    Ahmed, Abdelaal A; Abd-Elhady, Hany K

    2013-08-15

    The varroa mite, Varroa destructor (Anderson and Trueman) (Acari: Varroidae), is known as the most serious ectoparasitic mite on honeybee, Apis mellifera (Hymenoptera: Apidae) in the world. Based on the spores of entomopathogenic fungi, two commercial preparations; Bioranza (Metarhizium anisopliae) and Biovar (Beauveria bassiana) were evaluated through application into the hives against varroa mite. Data showed significant differences between treatments with Bioranza and Biovar, the results were significant after 7 and 14 days post-treatment. Mean a daily fallen mite individual was significantly different between the hives before and after the applications of the two biopesticides and wheat flour. Also, mites' mortality was, significantly, different between the hives before and after treatments. There were significant differences between treatments with the two biopesticides in worker's body weight. Bioranza and Biovar did not infect the honeybee in larval, prepupal, pupal and adult stages. Scanning and transmission electron microscopy images showed spores and hyphae penetration through stigma and wounds on varroa. The results suggest that Bioranza and Biovar are potentially are effective biopesticides against V. destructor in honeybee colonies.

  1. Ear mite infestation in four imported dogs from Thailand; a case report.

    PubMed

    Maazi, N; Jamshidi, Sh; Hadadzadeh, Hr

    2010-01-01

    Otodectes cynotis, ear mite or ear canker mite, is the most common cause of otitis external in cats (approximately 50%) and to a lesser extent in dogs, foxes and ferrets. The mite is living on the epidermal surface of auditory canal without burrowing into the tissue and feeding on tissue fluids and debris. In most of the cases they induce hypersensitivity reactions in the host. Four puppies; Siberian husky, Cocker spaniel, Terrier and mixed Pekignese with different genders and ages were referred to the Small Animal Hospital, Veterinary Faculty of Tehran University, Tehran, Iran for routine clinical examination just after they were imported from Thailand in a timeframe between June to August 2008.Clinical examinations showed an excessive dark brown discharge in both ears. No signs of other clinical situations were observed. White moving mites were seen during otoscopy examination, the specimen of ear discharge was sent to parasitology laboratory for precise identification of genus and species. Mites were identified as Otodectes cynotis and the presence of concurrent yeast and bacterial infection was showed by laboratory examinations. Topical Amitraz solution in combination with otic antibacterial and antifungal agents were administered as the treatment. Since, all the reported cases were imported from Thailand, careful clinical examination and quarantine strategies are highly recommended at the borders.

  2. Andes Hantavirus-Infection of a 3D Human Lung Tissue Model Reveals a Late Peak in Progeny Virus Production Followed by Increased Levels of Proinflammatory Cytokines and VEGF-A.

    PubMed

    Sundström, Karin B; Nguyen Hoang, Anh Thu; Gupta, Shawon; Ahlm, Clas; Svensson, Mattias; Klingström, Jonas

    2016-01-01

    Andes virus (ANDV) causes hantavirus pulmonary syndrome (HPS), a severe acute disease with a 40% case fatality rate. Humans are infected via inhalation, and the lungs are severely affected during HPS, but little is known regarding the effects of ANDV-infection of the lung. Using a 3-dimensional air-exposed organotypic human lung tissue model, we analyzed progeny virus production and cytokine-responses after ANDV-infection. After a 7-10 day period of low progeny virus production, a sudden peak in progeny virus levels was observed during approximately one week. This peak in ANDV-production coincided in time with activation of innate immune responses, as shown by induction of type I and III interferons and ISG56. After the peak in ANDV production a low, but stable, level of ANDV progeny was observed until 39 days after infection. Compared to uninfected models, ANDV caused long-term elevated levels of eotaxin-1, IL-6, IL-8, IP-10, and VEGF-A that peaked 20-25 days after infection, i.e., after the observed peak in progeny virus production. Notably, eotaxin-1 was only detected in supernatants from infected models. In conclusion, these findings suggest that ANDV replication in lung tissue elicits a late proinflammatory immune response with possible long-term effects on the local lung cytokine milieu. The change from an innate to a proinflammatory response might be important for the transition from initial asymptomatic infection to severe clinical disease, HPS.

  3. Andes Hantavirus-Infection of a 3D Human Lung Tissue Model Reveals a Late Peak in Progeny Virus Production Followed by Increased Levels of Proinflammatory Cytokines and VEGF-A.

    PubMed

    Sundström, Karin B; Nguyen Hoang, Anh Thu; Gupta, Shawon; Ahlm, Clas; Svensson, Mattias; Klingström, Jonas

    2016-01-01

    Andes virus (ANDV) causes hantavirus pulmonary syndrome (HPS), a severe acute disease with a 40% case fatality rate. Humans are infected via inhalation, and the lungs are severely affected during HPS, but little is known regarding the effects of ANDV-infection of the lung. Using a 3-dimensional air-exposed organotypic human lung tissue model, we analyzed progeny virus production and cytokine-responses after ANDV-infection. After a 7-10 day period of low progeny virus production, a sudden peak in progeny virus levels was observed during approximately one week. This peak in ANDV-production coincided in time with activation of innate immune responses, as shown by induction of type I and III interferons and ISG56. After the peak in ANDV production a low, but stable, level of ANDV progeny was observed until 39 days after infection. Compared to uninfected models, ANDV caused long-term elevated levels of eotaxin-1, IL-6, IL-8, IP-10, and VEGF-A that peaked 20-25 days after infection, i.e., after the observed peak in progeny virus production. Notably, eotaxin-1 was only detected in supernatants from infected models. In conclusion, these findings suggest that ANDV replication in lung tissue elicits a late proinflammatory immune response with possible long-term effects on the local lung cytokine milieu. The change from an innate to a proinflammatory response might be important for the transition from initial asymptomatic infection to severe clinical disease, HPS. PMID:26907493

  4. Light and scanning electron microscopic investigations on MiteStop-treated poultry red mites.

    PubMed

    Locher, Nina; Klimpel, Sven; Abdel-Ghaffar, Fathy; Al Rasheid, Khaled A S; Mehlhorn, Heinz

    2010-07-01

    Recent studies of the neem seed product MiteStop showed that it has a good acaricidal effect against all developmental stages of the poultry red mite, Dermanyssus gallinae. In vitro tests proved an efficacy at direct contact, as well as by fumigant toxicity. Light and scanning electron microscopic (SEM) investigations showed no clear, morphologically visible signs of an effect caused by fumigant toxicity. Direct contact with the neem product, however, seemed to be of great impact. Chicken mites turned dark brown or even black after being treated with the neem product. SEM analysis showed damages along the body surface of the mites. PMID:20563823

  5. Interleukin-1 alpha produced by human T-cell leukaemia virus type I-infected T cells induces intercellular adhesion molecule-1 expression on lung epithelial cells.

    PubMed

    Nakayama, Yuko; Ishikawa, Chie; Tamaki, Kazumi; Senba, Masachika; Fujita, Jiro; Mori, Naoki

    2011-12-01

    The pathogenic mechanism of human T-cell leukaemia virus type I (HTLV-I)-related pulmonary disease, which involves overexpression of intercellular adhesion molecule-1 (ICAM-1) in lung epithelial cells, was investigated. The supernatant of HTLV-I-infected Tax(+) MT-2 and C5/MJ cells induced ICAM-1 expression on A549 cells, a human tumour cell line with the properties of alveolar epithelial cells. Neutralization of ICAM-1 partially inhibited HTLV-I-infected T-cell adhesion to A549 cells. Analysis of the ICAM-1 promoter showed that the nuclear factor-kappa B-binding site was important for supernatant-induced ICAM-1 expression. Induction of interleukin (IL)-1 alpha (IL-1α) expression in MT-2 and C5/MJ cells was observed compared with uninfected controls and HTLV-I-infected Tax-negative cell lines. The significance of IL-1α as a soluble messenger was supported by blocking the biological activities of MT-2 supernatant with an IL-1α-neutralizing mAb. Moreover, Tax and IL-1α expression was demonstrated in the bronchoalveolar lavage cells of patients with HTLV-I-related pulmonary disease. Immunohistochemistry confirmed ICAM-1 and IL-1α expression in lung epithelial cells and lymphocytes of patients with HTLV-I-related pulmonary diseases, and in a transgenic mouse model of Tax expression. These results suggest that IL-1α produced by HTLV-I-infected Tax(+) T cells is crucial for ICAM-1 expression in lung epithelial cells and subsequent adhesion of lymphocytes in HTLV-I-related pulmonary diseases.

  6. Northern fowl mite (Ornithonyssus sylviarum) in Sweden.

    PubMed

    Jansson, D S; Otman, F; Lundqvist, L; Höglund, J; Engström, A; Chirico, J

    2014-12-01

    Haematophagous mites were collected from the vent region and plumage of chickens in six hobby flocks of ornamental breeds in Sweden, one of which included turkeys. Soiled vent skin and feathers, dermatitis, hyperkeratosis, skin necroses and ulcers were observed in 12 necropsied birds from two of the flocks. The mites were identified as the northern fowl mite Ornithonyssus sylviarum (Mesostigmata: Macronyssidae). This was supported by sequence analysis of a 642-bp region in the mitochondrial cytochrome oxidase subunit 1 (COI) gene (COI) in mites collected from five flocks, which showed 97-99% sequence similarity to O. sylviarum by blast analysis. Pairwise sequence comparisons revealed nucleotide variations in the range of 0-2.8%, whereas amino acid sequences were highly conserved. This paper represents one of very few records of O. sylviarum in European poultry, and is the first to report COI sequence data for O. sylviarum from poultry in Europe. PMID:24602037

  7. Myeloid-Restricted AMPKα1 Promotes Host Immunity and Protects against IL-12/23p40-Dependent Lung Injury during Hookworm Infection.

    PubMed

    Nieves, Wildaliz; Hung, Li-Yin; Oniskey, Taylor K; Boon, Louis; Foretz, Marc; Viollet, Benoit; Herbert, De'Broski R

    2016-06-01

    How the metabolic demand of parasitism affects immune-mediated resistance is poorly understood. Immunity against parasitic helminths requires M2 cells and IL-13, secreted by CD4(+) Th2 and group 2 innate lymphoid cells (ILC2), but whether certain metabolic enzymes control disease outcome has not been addressed. This study demonstrates that AMP-activated protein kinase (AMPK), a key driver of cellular energy, regulates type 2 immunity and restricts lung injury following hookworm infection. Mice with a selective deficiency in the AMPK catalytic α1 subunit in alveolar macrophages and conventional dendritic cells produced less IL-13 and CCL17 and had impaired expansion of ILC2 in damaged lung tissue compared with wild-type controls. Defective type 2 responses were marked by increased intestinal worm burdens, exacerbated lung injury, and increased production of IL-12/23p40, which, when neutralized, restored IL-13 production and improved lung recovery. Taken together, these data indicate that defective AMPK activity in myeloid cells negatively impacts type 2 responses through increased IL-12/23p40 production. These data support an emerging concept that myeloid cells and ILC2 can coordinately regulate tissue damage at mucosal sites through mechanisms dependent on metabolic enzyme function. PMID:27183598

  8. Characterization of Nontypable Haemophilus influenzae Isolates Recovered from Adult Patients with Underlying Chronic Lung Disease Reveals Genotypic and Phenotypic Traits Associated with Persistent Infection

    PubMed Central

    Garmendia, Junkal; Viadas, Cristina; Calatayud, Laura; Mell, Joshua Chang; Martí-Lliteras, Pau; Euba, Begoña; Llobet, Enrique; Gil, Carmen; Bengoechea, José Antonio; Redfield, Rosemary J.; Liñares, Josefina

    2014-01-01

    Nontypable Haemophilus influenzae (NTHi) has emerged as an important opportunistic pathogen causing infection in adults suffering obstructive lung diseases. Existing evidence associates chronic infection by NTHi to the progression of the chronic respiratory disease, but specific features of NTHi associated with persistence have not been comprehensively addressed. To provide clues about adaptive strategies adopted by NTHi during persistent infection, we compared sequential persistent isolates with newly acquired isolates in sputa from six patients with chronic obstructive lung disease. Pulse field gel electrophoresis (PFGE) identified three patients with consecutive persistent strains and three with new strains. Phenotypic characterisation included infection of respiratory epithelial cells, bacterial self-aggregation, biofilm formation and resistance to antimicrobial peptides (AMP). Persistent isolates differed from new strains in showing low epithelial adhesion and inability to form biofilms when grown under continuous-flow culture conditions in microfermenters. Self-aggregation clustered the strains by patient, not by persistence. Increasing resistance to AMPs was observed for each series of persistent isolates; this was not associated with lipooligosaccharide decoration with phosphorylcholine or with lipid A acylation. Variation was further analyzed for the series of three persistent isolates recovered from patient 1. These isolates displayed comparable growth rate, natural transformation frequency and murine pulmonary infection. Genome sequencing of these three isolates revealed sequential acquisition of single-nucleotide variants in the AMP permease sapC, the heme acquisition systems hgpB, hgpC, hup and hxuC, the 3-deoxy-D-manno-octulosonic acid kinase kdkA, the long-chain fatty acid transporter ompP1, and the phosphoribosylamine glycine ligase purD. Collectively, we frame a range of pathogenic traits and a repertoire of genetic variants in the context of

  9. Personality and ectoparasitic mites (Hemipteroseius adleri) in firebugs (Pyrrhocoris apterus).

    PubMed

    Gyuris, Enikő; Hankó, Júlia Fruzsina; Feró, Orsolya; Barta, Zoltán

    2016-01-01

    Individuals of the same species often consistently differ in their behaviour across time and context. These stable differences are usually termed 'animal personality'. Parasitism is known to significantly influence the evolution of animal personality at least in part because more explorative individuals may meet parasites more frequently than less explorative ones. Previously, we have demonstrated that consistent individual differences (i.e. boldness, activity, exploration) can be measured in firebugs. As continuation, we examined here the relationship between firebug personality traits and their ectoparasitic mite loads in a wild population. We showed that bugs that behaved in a more explorative way have more mites and we also found a marginally significant interaction between sex, boldness and activity: bolder and more active female firebugs were more infected. In addition, we experimentally tested whether an artificial infection causes any alteration in the bug's behaviour and whether there is any relationship between firebug personality and immune response. This treatment did not induce any alteration in bugs' personality. We found that bugs become more explorative but less active when repeating the experiment, but at the same time all personality traits (boldness, activity and exploration) were repeatable. Furthermore, firebugs with a stronger immune response behaved more boldly but also less actively. PMID:26569455

  10. Personality and ectoparasitic mites (Hemipteroseius adleri) in firebugs (Pyrrhocoris apterus).

    PubMed

    Gyuris, Enikő; Hankó, Júlia Fruzsina; Feró, Orsolya; Barta, Zoltán

    2016-01-01

    Individuals of the same species often consistently differ in their behaviour across time and context. These stable differences are usually termed 'animal personality'. Parasitism is known to significantly influence the evolution of animal personality at least in part because more explorative individuals may meet parasites more frequently than less explorative ones. Previously, we have demonstrated that consistent individual differences (i.e. boldness, activity, exploration) can be measured in firebugs. As continuation, we examined here the relationship between firebug personality traits and their ectoparasitic mite loads in a wild population. We showed that bugs that behaved in a more explorative way have more mites and we also found a marginally significant interaction between sex, boldness and activity: bolder and more active female firebugs were more infected. In addition, we experimentally tested whether an artificial infection causes any alteration in the bug's behaviour and whether there is any relationship between firebug personality and immune response. This treatment did not induce any alteration in bugs' personality. We found that bugs become more explorative but less active when repeating the experiment, but at the same time all personality traits (boldness, activity and exploration) were repeatable. Furthermore, firebugs with a stronger immune response behaved more boldly but also less actively.

  11. A Quadruple Knockout of lasIR and rhlIR of Pseudomonas aeruginosa PAO1 That Retains Wild-Type Twitching Motility Has Equivalent Infectivity and Persistence to PAO1 in a Mouse Model of Lung Infection

    PubMed Central

    Lazenby, James J.; Griffin, Phoebe E.; Kyd, Jennelle; Whitchurch, Cynthia B.; Cooley, Margaret A.

    2013-01-01

    It has been widely reported that quorum-sensing incapable strains of Pseudomonas aeruginosa are less virulent than wild type strains. However, quorum sensing mutants of P. aeruginosa have been shown to develop other spontaneous mutations under prolonged culture conditions, and one of the phenotypes of P. aeruginosa that is frequently affected by this phenomenon is type IV pili-dependent motility, referred to as twitching motility. As twitching motility has been reported to be important for adhesion and colonisation, we aimed to generate a quorum-sensing knockout for which the heritage was recorded and the virulence factor production in areas unrelated to quorum sensing was known to be intact. We created a lasIRrhlIR quadruple knockout in PAO1 using a published technique that allows for the deletion of antibiotic resistance cartridges following mutagenesis, to create an unmarked QS knockout of PAO1, thereby avoiding the need for use of antibiotics in culturing, which can have subtle effects on bacterial phenotype. We phenotyped this mutant demonstrating that it produced reduced levels of protease and elastase, barely detectable levels of pyoverdin and undetectable levels of the quorum sensing signal molecules N-3-oxododecanoly-L-homoserine lactone and N-butyryl homoserine lactone, but retained full twitching motility. We then used a mouse model of acute lung infection with P. aeruginosa to demonstrate that the lasIRrhlIR knockout strain showed equal persistence to wild type parental PAO1, induced equal or greater neutrophil infiltration to the lungs, and induced similar levels of expression of inflammatory cytokines in the lungs and similar antibody responses, both in terms of magnitude and isotype. Our results suggest, in contrast to previous reports, that lack of quorum sensing alone does not significantly affect the immunogenicity, infectiveness and persistence of P. aeruginosa in a mouse model of acute lung infection. PMID:23593362

  12. The role of mites in insect-fungus associations.

    PubMed

    Hofstetter, R W; Moser, J C

    2014-01-01

    The interactions among insects, mites, and fungi are diverse and complex but poorly understood in most cases. Associations among insects, mites, and fungi span an almost incomprehensible array of ecological interactions and evolutionary histories. Insects and mites often share habitats and resources and thus interact within communities. Many mites and insects rely on fungi for nutrients, and fungi benefit from them with regard to spore dispersal, habitat provision, or nutrient resources. Mites have important impacts on community dynamics, ecosystem processes, and biodiversity within many insect-fungus systems. Given that mites are understudied but highly abundant, they likely have bigger, more important, and more widespread impacts on communities than previously recognized. We describe mutualistic and antagonistic effects of mites on insect-fungus associations, explore the processes that underpin ecological and evolutionary patterns of these multipartite communities, review well-researched examples of the effects of mites on insect-fungus associations, and discuss approaches for studying mites within insect-fungus communities.

  13. Inactivation of dust mites, dust mite allergen, and mold from carpet.

    PubMed

    Ong, Kee-Hean; Lewis, Roger D; Dixit, Anupma; MacDonald, Maureen; Yang, Mingan; Qian, Zhengmin

    2014-01-01

    Carpet is known to be a reservoir for biological contaminants, such as dust mites, dust mite allergen, and mold, if it is not kept clean. The accumulation of these contaminants in carpet might trigger allergies or asthma symptoms in both children and adults. The purpose of this study is to compare methods for removal of dust mites, dust mite allergens, and mold from carpet. Carpets were artificially worn to simulate 1 to 2 years of wear in a four-person household. The worn carpets were inoculated together with a common indoor mold (Cladosporium species) and house dust mites and incubated for 6 weeks to allow time for dust mite growth on the carpet. The carpets were randomly assigned to one of the four treatment groups. Available treatment regimens for controlling carpet contaminants were evaluated through a literature review and experimentation. Four moderately low-hazard, nondestructive methods were selected as treatments: vacuuming, steam-vapor, Neem oil (a natural tree extract), and benzalkonium chloride (a quaternary ammonium compound). Steam vapor treatment demonstrated the greatest dust mite population reduction (p < 0.05) when compared to other methods. The two physical methods, steam vapor and vacuuming, have no statistically significant efficacy in inactivating dust mite allergens (p = 0.084), but have higher efficacy when compared to the chemical method on dust mite allergens (p = 0.002). There is no statistically significant difference in the efficacy for reducing mold in carpet (p > 0.05) for both physical and chemical methods. The steam-vapor treatment effectively killed dust mites and denatured dust mite allergen in the laboratory environment. PMID:24467247

  14. Inactivation of dust mites, dust mite allergen, and mold from carpet.

    PubMed

    Ong, Kee-Hean; Lewis, Roger D; Dixit, Anupma; MacDonald, Maureen; Yang, Mingan; Qian, Zhengmin

    2014-01-01

    Carpet is known to be a reservoir for biological contaminants, such as dust mites, dust mite allergen, and mold, if it is not kept clean. The accumulation of these contaminants in carpet might trigger allergies or asthma symptoms in both children and adults. The purpose of this study is to compare methods for removal of dust mites, dust mite allergens, and mold from carpet. Carpets were artificially worn to simulate 1 to 2 years of wear in a four-person household. The worn carpets were inoculated together with a common indoor mold (Cladosporium species) and house dust mites and incubated for 6 weeks to allow time for dust mite growth on the carpet. The carpets were randomly assigned to one of the four treatment groups. Available treatment regimens for controlling carpet contaminants were evaluated through a literature review and experimentation. Four moderately low-hazard, nondestructive methods were selected as treatments: vacuuming, steam-vapor, Neem oil (a natural tree extract), and benzalkonium chloride (a quaternary ammonium compound). Steam vapor treatment demonstrated the greatest dust mite population reduction (p < 0.05) when compared to other methods. The two physical methods, steam vapor and vacuuming, have no statistically significant efficacy in inactivating dust mite allergens (p = 0.084), but have higher efficacy when compared to the chemical method on dust mite allergens (p = 0.002). There is no statistically significant difference in the efficacy for reducing mold in carpet (p > 0.05) for both physical and chemical methods. The steam-vapor treatment effectively killed dust mites and denatured dust mite allergen in the laboratory environment.

  15. Novel scabies mite serpins inhibit the three pathways of the human complement system.

    PubMed

    Mika, Angela; Reynolds, Simone L; Mohlin, Frida C; Willis, Charlene; Swe, Pearl M; Pickering, Darren A; Halilovic, Vanja; Wijeyewickrema, Lakshmi C; Pike, Robert N; Blom, Anna M; Kemp, David J; Fischer, Katja

    2012-01-01

    Scabies is a parasitic infestation of the skin by the mite Sarcoptes scabiei that causes significant morbidity worldwide, in particular within socially disadvantaged populations. In order to identify mechanisms that enable the scabies mite to evade human immune defenses, we have studied molecules associated with proteolytic systems in the mite, including two novel scabies mite serine protease inhibitors (SMSs) of the serpin superfamily. Immunohistochemical studies revealed that within mite-infected human skin SMSB4 (54 kDa) and SMSB3 (47 kDa) were both localized in the mite gut and feces. Recombinant purified SMSB3 and SMSB4 did not inhibit mite serine and cysteine proteases, but did inhibit mammalian serine proteases, such as chymotrypsin, albeit inefficiently. Detailed functional analysis revealed that both serpins interfered with all three pathways of the human complement system at different stages of their activation. SMSB4 inhibited mostly the initial and progressing steps of the cascades, while SMSB3 showed the strongest effects at the C9 level in the terminal pathway. Additive effects of both serpins were shown at the C9 level in the lectin pathway. Both SMSs were able to interfere with complement factors without protease function. A range of binding assays showed direct binding between SMSB4 and seven complement proteins (C1, properdin, MBL, C4, C3, C6 and C8), while significant binding of SMSB3 occurred exclusively to complement factors without protease function (C4, C3, C8). Direct binding was observed between SMSB4 and the complement proteases C1s and C1r. However no complex formation was observed between either mite serpin and the complement serine proteases C1r, C1s, MASP-1, MASP-2 and MASP-3. No catalytic inhibition by either serpin was observed for any of these enzymes. In summary, the SMSs were acting at several levels mediating overall inhibition of the complement system and thus we propose that they may protect scabies mites from complement

  16. Genotypic variability and relationships between mite infestation levels, mite damage, grooming intensity, and removal of Varroa destructor mites in selected strains of worker honey bees (Apis mellifera L.).

    PubMed

    Guzman-Novoa, Ernesto; Emsen, Berna; Unger, Peter; Espinosa-Montaño, Laura G; Petukhova, Tatiana

    2012-07-01

    The objective of this study was to demonstrate genotypic variability and analyze the relationships between the infestation levels of the parasitic mite Varroa destructor in honey bee (Apis mellifera) colonies, the rate of damage of fallen mites, and the intensity with which bees of different genotypes groom themselves to remove mites from their bodies. Sets of paired genotypes that are presumably susceptible and resistant to the varroa mite were compared at the colony level for number of mites falling on sticky papers and for proportion of damaged mites. They were also compared at the individual level for intensity of grooming and mite removal success. Bees from the "resistant" colonies had lower mite population rates (up to 15 fold) and higher percentages of damaged mites (up to 9 fold) than bees from the "susceptible" genotypes. At the individual level, bees from the "resistant" genotypes performed significantly more instances of intense grooming (up to 4 fold), and a significantly higher number of mites were dislodged from the bees' bodies by intense grooming than by light grooming (up to 7 fold) in all genotypes. The odds of mite removal were high and significant for all "resistant" genotypes when compared with the "susceptible" genotypes. The results of this study strongly suggest that grooming behavior and the intensity with which bees perform it, is an important component in the resistance of some honey bee genotypes to the growth of varroa mite populations. The implications of these results are discussed.

  17. Identification of interleukin-1, tumor necrosis factor-alpha, and interleukin-6 expression in lungs from pigs naturally infected with Mycoplasma hyopneumoniae by in situ hybridization.

    PubMed

    Ahn, Kyoung Kyu; Kwon, Donghyeok; Jung, Kwonil; Ha, Yooncheol; Seo, Man Jun; Kim, Sung-Hoon; Kim, Mi-Young; Cho, Kyung-Dong; Lee, Bog-Hieu; Chae, Chanhee

    2009-04-01

    The detection and distribution of interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha) and IL-6 were studied, by in situ hybridization with a non-radioactive digoxigenin-labeled probe, in formalin-fixed, paraffin-embedded lung tissue from 10 pigs naturally infected with Mycoplasma hyopneumoniae. The morphology of host cells was preserved despite the relatively high temperature required during the incubation procedure. Examination of three serial sections from each of the 10 lung samples showed that the three cytokines closely resembled each other in respect of cellular distribution. Three inflammatory cytokines are expressed in response to M. hyopneumoniae infection, with IL-6 localized primarily to peribronchiolar lymphoid hyperplastic tissues, and both IL-1 and TNF-alpha expressed in alveolar macrophages. Although statistically non-significant, IL-1 (r=0.5744, p=0.0883) showed potentially important correlation with histopatholgical lesions. No other potentially clinically important correlations (r>0.30) were observed between any of the other cytokines (TNF-alpha; r=0.2045, p=0.5603 and IL-6; r=-0.06607, p=0.8651) and histopathological lesion score. The results suggest that inflammatory cytokines are associated with the development of pneumonia in M. hyopneumoniae infection and may contribute to disease severity.

  18. Spectral response of spider mite infested cotton: Mite density and miticide rate study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two-spotted spider mites are important pests in many agricultural systems. Spider mites (Acari: Tetranychidae) have been found to cause economic damage in corn, cotton, and sorghum. Adult glass vial bioassays indicate that Temprano™ (abamectin) is the most toxic technical miticide for adult two-spot...

  19. Mitochondrial genome evolution and tRNA truncation in Acariformes mites: new evidence from eriophyoid mites

    PubMed Central

    Xue, Xiao-Feng; Guo, Jing-Feng; Dong, Yan; Hong, Xiao-Yue; Shao, Renfu

    2016-01-01

    The subclass Acari (mites and ticks) comprises two super-orders: Acariformes and Parasitiformes. Most species of the Parasitiformes known retained the ancestral pattern of mitochondrial (mt) gene arrangement of arthropods, and their mt tRNAs have the typical cloverleaf structure. All of the species of the Acariformes known, however, have rearranged mt genomes and truncated mt tRNAs. We sequenced the mt genomes of two species of Eriophyoidea: Phyllocoptes taishanensis and Epitrimerus sabinae. The mt genomes of P. taishanensis and E. sabinae are 13,475 bp and 13,531 bp, respectively, are circular and contain the 37 genes typical of animals; most mt tRNAs are highly truncated in both mites. On the other hand, these two eriophyoid mites have the least rearranged mt genomes seen in the Acariformes. Comparison between eriophyoid mites and other Aacariformes mites showed that: 1) the most recent common ancestor of Acariformes mites retained the ancestral pattern of mt gene arrangement of arthropods with slight modifications; 2) truncation of tRNAs for cysteine, phenylalanine and histidine occurred once in the most recent common ancestor of Acariformes mites whereas truncation of other tRNAs occurred multiple times; and 3) the placement of eriophyoid mites in the order Trombidiformes needs to be reviewed. PMID:26732998

  20. Wheat curl mite and dry bulb mite: untangling a taxonomic conundrum through a multidisciplinary approach

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The taxonomy of two economically important eriophyoid species, Aceria tosichella (wheat curl mite, WCM) and A. tulipae (dry bulb mite, DBM), was confounded in the world literature until the late 20th century due to their morphological similarity and ambiguous data from plant-transfer and virus-trans...

  1. Genetic epidemiology and pathology of raccoon-derived Sarcoptes mites from urban areas of Germany.

    PubMed

    Rentería-Solís, Z; Min, A M; Alasaad, S; Müller, K; Michler, F-U; Schmäschke, R; Wittstatt, U; Rossi, L; Wibbelt, G

    2014-08-01

    The raccoon, Procyon lotor (Carnivora: Procyonidae), is an invasive species that is spreading throughout Europe, in which Germany represents its core area. Here, raccoons mostly live in rural regions, but some urban populations are already established, such as in the city of Kassel, or are starting to build up, such as in Berlin. The objective of this study was to investigate Sarcoptes (Sarcoptiformes: Sarcoptidae) infections in racoons in these two urban areas and to identify the putative origin of the parasite. Parasite morphology, and gross and histopathological examinations of diseased skin tissue were consistent with Sarcoptes scabiei infection. Using nine microsatellite markers, we genotyped individual mites from five raccoons and compared them with Sarcoptes mites derived from fox, wild boar and Northern chamois, originating from Italy and Switzerland. The raccoon-derived mites clustered together with the fox samples and were clearly differentiated from those of the wild boar and chamois samples, which suggests a fox origin for the raccoon mange infection. These results are evidence of the cross-transmission of S. scabiei among wild carnivores. Although our results cannot elucidate whether raccoons became infected by frequent interaction with endemically or epidemically infected foxes or whether these cases resulted from occasional contacts among these animal species, they do nevertheless show that pathogens can be shared among urban populations of native and invasive carnivores.

  2. Genetic epidemiology and pathology of raccoon-derived Sarcoptes mites from urban areas of Germany.

    PubMed

    Rentería-Solís, Z; Min, A M; Alasaad, S; Müller, K; Michler, F-U; Schmäschke, R; Wittstatt, U; Rossi, L; Wibbelt, G

    2014-08-01

    The raccoon, Procyon lotor (Carnivora: Procyonidae), is an invasive species that is spreading throughout Europe, in which Germany represents its core area. Here, raccoons mostly live in rural regions, but some urban populations are already established, such as in the city of Kassel, or are starting to build up, such as in Berlin. The objective of this study was to investigate Sarcoptes (Sarcoptiformes: Sarcoptidae) infections in racoons in these two urban areas and to identify the putative origin of the parasite. Parasite morphology, and gross and histopathological examinations of diseased skin tissue were consistent with Sarcoptes scabiei infection. Using nine microsatellite markers, we genotyped individual mites from five raccoons and compared them with Sarcoptes mites derived from fox, wild boar and Northern chamois, originating from Italy and Switzerland. The raccoon-derived mites clustered together with the fox samples and were clearly differentiated from those of the wild boar and chamois samples, which suggests a fox origin for the raccoon mange infection. These results are evidence of the cross-transmission of S. scabiei among wild carnivores. Although our results cannot elucidate whether raccoons became infected by frequent interaction with endemically or epidemically infected foxes or whether these cases resulted from occasional contacts among these animal species, they do nevertheless show that pathogens can be shared among urban populations of native and invasive carnivores. PMID:25171612

  3. Developing Optimal Parameters for Hyperpolarized Noble Gas and Inert Fluorinated Gas MRI of Lung Disorders

    ClinicalTrials.gov

    2016-04-19

    Lung Transplant; Lung Resection; Lung Cancer; Asthma; Cystic Fibrosis; Chronic Obstructive Pulmonary Disease; Emphysema; Mesothelioma; Asbestosis; Pulmonary Embolism; Interstitial Lung Disease; Pulmonary Fibrosis; Bronchiectasis; Seasonal Allergies; Cold Virus; Lung Infection; Pulmonary Hypertension; Pulmonary Dysplasia; Obstructive Sleep Apnea

  4. Low or high doses of cefquinome targeting low or high bacterial inocula cure Klebsiella pneumoniae lung infections but differentially impact the levels of antibiotic resistance in fecal flora.

    PubMed

    Vasseur, Maleck V; Laurentie, Michel; Rolland, Jean-Guy; Perrin-Guyomard, Agnès; Henri, Jérôme; Ferran, Aude A; Toutain, Pierre-Louis; Bousquet-Mélou, Alain

    2014-01-01

    The combination of efficacious treatment against bacterial infections and mitigation of antibiotic resistance amplification in gut microbiota is a major challenge for antimicrobial therapy in food-producing animals. In rats, we evaluated the impact of cefquinome, a fourth-generation cephalosporin, on both Klebsiella pneumoniae lung infection and intestinal flora harboring CTX-M-producing Enterobacteriaceae. Germfree rats received a fecal flora specimen from specific-pathogen-free pigs, to which a CTX-M-producing Escherichia coli strain had been added. K. pneumoniae cells were inoculated in the lungs of these gnotobiotic rats by using either a low (10(5) CFU) or a high (10(9) CFU) inoculum. Without treatment, all animals infected with the low or high K. pneumoniae inoculum developed pneumonia and died before 120 h postchallenge. In the treated groups, the low-inoculum rats received a 4-day treatment of 5 mg/kg of body weight cefquinome beginning at 24 h postchallenge (prepatent phase of the disease), and the high-inoculum rats received a 4-day treatment of 50 mg/kg cefquinome beginning when the animals expressed clinical signs of infection (patent phase of the disease). The dose of 50 mg/kg targeting the high K. pneumoniae inoculum cured all the treated rats and resulted in a massive amplification of CTX-M-producing Enterobacteriaceae. A dose of 5 mg/kg targeting the low K. pneumoniae inoculum cured all the rats and averted an outbreak of clinical disease, all without any amplification of CTX-M-producing Enterobacteriaceae. These findings might have implications for the development of new antimicrobial treatment strategies that ensure a cure for bacterial infections while avoiding the amplification of resistance genes of human concern in the gut microbiota of food-producing animals.

  5. Experimental study on possible transmission of the bacterium Erysipelothrix rhusiopathiae to chickens by the poultry red mite, Dermanyssus gallinae.

    PubMed

    Brännström, Sara; Hansson, Ingrid; Chirico, Jan

    2010-04-01

    The vector potential of the poultry red mite, Dermanyssus gallinae De Geer (Acari: Dermanyssidae), in relation to chicken erysipelas was investigated under experimental conditions. Chickens were inoculated intramuscularly with the bacterium Erysipelothrix rhusiopathiae, and mites were allowed to feed on the inoculated chickens for 5 days. After 20 days of starvation, the mites were allowed to feed on healthy chickens to enable transmission of bacteria. Blood samples were collected from the birds and analysed for the presence of E. rhusiopathiae, and ELISA tests were performed for seropositivity. The internal presence of E. rhusiopathiae in the mites after feeding of inoculated birds was also investigated. It could not be demonstrated that mites take up and transmit E. rhusiopathiae under the experimental conditions described. However, since there are case reports as well as other in vitro studies indicating the potential of D. gallinae to act as a reservoir and potential vector for infections agents, we cannot exclude the possibility that the red poultry mite transmits E. rhusiopathiae between chickens under field conditions.

  6. Transcriptomic and Epigenetic Profiling of the Lung of Influenza-Infected Pigs: A Comparison of Different Birth Weight and Susceptibility Groups

    PubMed Central

    Wilkinson, Jamie M.; Gunvaldsen, Rayna E.; Detmer, Susan E.; Dyck, Michael K.; Dixon, Walter T.; Foxcroft, George R.; Plastow, Graham S.; Harding, John C. S.

    2015-01-01

    Influenza viruses are a common cause of respiratory disease in swine. Infections range in severity from asymptomatic to causing significant morbidity. The main objective of this study was to compare lung transcriptomic and epigenetic responses to influenza infection in pigs from high or low birth weight litters. The latter is a potential indicator of intrauterine growth restriction, a significant risk factor for prenatal programming effects. Individual pigs from high (HBW) or low birth weight (LBW) litters (n = 17) were inoculated with influenza A virus and euthanized 48 hours later. Lesion severity and viral loads were assessed as previously described. The transcriptional response to infection in LBW and HBW groups (n = 16) was assessed by microarray. A separate analysis of pigs classified as ‘Resilient’ (RES) or ‘Susceptible’ (SUS) (n = 6) on the basis of severity of lung pathology was also conducted. Eight genes were confirmed as differentially expressed for the birth weight comparison, including three antiviral genes with lower expression in LBW: ISG15, OAS1, and OAS2 (P<0.05). The promoter region methylation status of these three genes was assessed for each birth weight group, and no differences were found. These expression data are consistent with our previous finding that LBW pigs had less severe lesion scores and a trend towards lower viral titres in lung than the HBW cohort. The SUS v RES comparison identified 91 differentially expressed genes (FDR<0.05) that were enriched with functional annotation terms and pathways associated with inflammation. The cytokine genes IL6, IL8, and CCL2 were all upregulated in SUS pigs, and may have driven disease severity in these animals. In conclusion, this study found no evidence that the transcriptional immune response to influenza was adversely affected by low litter birth weight, but did identify several candidate genes for driving disease pathology. PMID:26393920

  7. Seoul virus-infected rat lung endothelial cells and alveolar macrophages differ in their ability to support virus replication and induce regulatory T cell phenotypes.

    PubMed

    Li, Wei; Klein, Sabra L

    2012-11-01

    Hantaviruses cause a persistent infection in reservoir hosts that is attributed to the upregulation of regulatory responses and downregulation of proinflammatory responses. To determine whether rat alveolar macrophages (AMs) and lung microvascular endothelial cells (LMVECs) support Seoul virus (SEOV) replication and contribute to the induction of an environment that polarizes CD4(+) T cell differentiation toward a regulatory T (Treg) cell phenotype, cultured primary rat AMs and LMVECs were mock infected or infected with SEOV and analyzed for viral replication, cytokine and chemokine responses, and expression of cell surface markers that are related to T cell activation. Allogeneic CD4(+) T cells were cocultured with SEOV-infected or mock-infected AMs or LMVECs and analyzed for helper T cell (i.e., Treg, Th17, Th1, and Th2) marker expression and Treg cell frequency. SEOV RNA and infectious particles in culture media were detected in both cell types, but at higher levels in LMVECs than in AMs postinfection. Expression of Ifnβ, Ccl5, and Cxcl10 and surface major histocompatibility complex class II (MHC-II) and MHC-I was not altered by SEOV infection in either cell type. SEOV infection significantly increased Tgfβ mRNA in AMs and the amount of programmed cell death 1 ligand 1 (PD-L1) in LMVECs. SEOV-infected LMVECs, but not AMs, induced a significant increase in Foxp3 expression and Treg cell frequency in allogeneic CD4(+) T cells, which was virus replication and cell contact dependent. These data suggest that in addition to supporting viral replication, AMs and LMVECs play distinct roles in hantavirus persistence by creating a regulatory environment through increased Tgfβ, PD-L1, and Treg cell activity.

  8. Infection.

    PubMed

    Miclau, Theodore; Schmidt, Andrew H; Wenke, Joseph C; Webb, Lawrence X; Harro, Janette M; Prabhakara, Ranjani; Shirtliff, Mark E

    2010-09-01

    Musculoskeletal infection is a clinical problem with significant direct healthcare costs. The prevalence of infection after closed, elective surgery is frequently estimated to be less than 2%, but in severe injuries, posttraumatic infection rates have been reported as 10% or greater. Although clinical infections are found outside the realm of medical devices, it is clear that the enormous increase of infections associated with the use of implants presents a major challenge worldwide. This review summarizes recent advances in the understanding, diagnosis, and treatment of musculoskeletal infections.

  9. CFTR and lung homeostasis.

    PubMed

    Collawn, James F; Matalon, Sadis

    2014-12-15

    CFTR is a cAMP-activated chloride and bicarbonate channel that is critical for lung homeostasis. Decreases in CFTR expression have dire consequences in cystic fibrosis (CF) and have been suggested to be a component of the lung pathology in chronic obstructive pulmonary disease. Decreases or loss of channel function often lead to mucus stasis, chronic bacterial infections, and the accompanying chronic inflammatory responses that promote progressive lung destruction, and, eventually in CF, lung failure. Here we discuss CFTR's functional role airway surface liquid hydration and pH, in regulation of other channels such as the epithelial sodium channel, and in regulating inflammatory responses in the lung. PMID:25381027

  10. [Sensitization to granary mites in patients with allergic diseases].

    PubMed

    Golysheva, M A

    1991-01-01

    As many as 71 patients selected from a group of 550 patients suffering from allergic diseases, sensitized to the house dust mites Dermatophagoides pteronyssinus were examined. A study was made of the presence of allergen-specific IgE antibodies against house dust mites, storage mites (7 species altogether) using allergenic discs and commercial kits RAST (Pharmacia, Sweden). The group under examination mostly manifested sensitization to the house dust mites: Dermatophagoides ferinae (80%), Euroglyphus maynei (55%); storage mites: Acarus siro (45%), Lepidoglyphus destructor (35%). The latter one possesses the most powerful allergenic properties as compared to the acaroid mites of other types. The elevated sensitivity to storage mites is encountered among adults and children living both in Moscow and other regions (urban and rural). The problem of sensitization to storage mites in the USSR mandates thorough studies, which will enable the treatment and diagnostic agents to be designed and introduced into practice.

  11. Colonization and organ invasion in chicks experimentally infected with Dermanyssus gallinae contaminated by Salmonella Enteritidis.

    PubMed

    Moro, Claire Valiente; Fravalo, Philippe; Amelot, Michel; Chauve, Claude; Zenner, Lionel; Salvat, Gilles

    2007-08-01

    The poultry red mite (Dermanyssus gallinae) is the most important and common ectoparasite of laying hens in Europe. This haematophagous mite has been experimentally demonstrated to be a vector of Salmonella Enteritidis by acquiring bacteria through the blood meal or cuticular contact. We have evaluated another route of infection by orally inoculating chicks with mites previously infected by S. Enteritidis. Two methods of infecting the mites were tested: mites contaminated by cuticular contact or during the blood meal. After the washing of mites with paraformaldehyde, groups of 10 Salmonella-contaminated mites were inoculated individually into 1-day-old chicks. The titre of the inoculum suspension was evaluated by crushing mites and followed by bacteriological counting. It was 3x10(4) colony-forming units/chick and 2.7x10(6) colony-forming units/chick, respectively, for cuticular contact and orally mediated contamination of mites. Each bird was found to be positive 12 days post-inoculation. Salmonella colonized the intestinal tracts and invaded the livers and spleens. The caecal content concentration reached a mean level of S. Enteritidis of 8.5x10(4) most probable number (MPN) Salmonella/g. This experiment demonstrated the ability of mites to orally infect 1-day-old chicks with subsequent colonization and multiplication of Salmonella. Consequently, mites infected by S. Enteritidis constitute potential reservoir hosts of this bacterium, allowing it to persist in the poultry house as a source of infection for newly introduced animals. If contaminated mites are found in poultry facilities, effective red mite control should be performed before new batches are introduced into the facility.

  12. Structural and functional changes in pulmonary macrophages and lungs of mice infected with influenza virus A/H5N1 A/goose/Krasnoozerskoye/627/05.

    PubMed

    Kovner, A V; Anikina, A G; Potapova, O V; Sharkova, T V; Cherdanceva, L A; Shkurupy, V A; Shestopalov, A M

    2012-06-01

    C57Bl/6 mice were intranasally infected with influenza virus A/H5N1 A/goose/Krasnoozerskoye/627/05. The mortality rate of animals reached 70% on day 14 of the disease. The lungs of animals were characterized by necroses, destruction of vessels, hemorrhagic and thrombotic complications, edematous syndrome, and early fibrosis of the interstitium. On days 6-10 after infection, fibrosis was found in the zones of postnecrotic inflammatory infiltration. The expression of lysozyme and myeloperoxidase by pulmonary macrophages was initially increased, but decreased on day 10 of the study. The number of cathepsin D-expressing macrophages was elevated up to the 10th day of examination.

  13. Rebamipide suppresses mite-induced asthmatic responses in NC/Nga mice.

    PubMed

    Murakami, Ikuo; Zhang, Ran; Kubo, Masayuki; Nagaoka, Kenjiro; Eguchi, Eri; Ogino, Keiki

    2015-10-15

    Allergic asthma caused by continuous allergen exposure evokes allergen-specific Th2 responses and is characterized by chronic airway inflammation and hyperresponsiveness. A previous report showed that rebamipide improved asthmatic symptoms in an ovalbumin/trypsin mice model. However, it is still unclear how rebamipide exerts its effects in asthma. In this study, rebamipide improved the asthmatic responses induced by mite exposure in NC/Nga mice, revealing the mechanism of this therapeutic effect. Rebamipide suppressed the infiltration of eosinophils into the airways and lung as well as attenuating the production of reactive oxygen species in tissues. In addition to these anti-inflammatory effects, rebamipide inhibited the production of IL-33, a member of the IL-1 family that drives the subsequent production of Th2-associated cytokines. These observations identify the point where rebamipide exerts its suppressive action on asthma and suggest that rebamipide has therapeutic potential in preventing mite-induced asthma. PMID:26472814

  14. The α-Tocopherol Form of Vitamin E Reverses Age-Associated Susceptibility to Streptococcus pneumoniae Lung Infection by Modulating Pulmonary Neutrophil Recruitment

    PubMed Central

    Ghanem, Elsa N. Bou; Clark, Stacie; Du, Xiaogang; Wu, Dayong; Camilli, Andrew; Leong, John M.; Meydani, Simin N.

    2016-01-01

    Streptococcus pneumoniae infections are an important cause of morbidity and mortality in older patients. Uncontrolled neutrophil-driven pulmonary inflammation exacerbates this disease. To test whether the α-tocopherol (α-Toc) form of vitamin E, a regulator of immunity, can modulate neutrophil responses as a preventive strategy to mitigate the age-associated decline in resistance to S. pneumoniae, young (4 mo) and old (22–24 mo) C57BL/6 mice were fed a diet containing 30-PPM (control) or 500-PPM (supplemented) α-Toc for 4 wk and intratracheally infected with S. pneumoniae. Aged mice fed a control diet were exquisitely more susceptible to S. pneumoniae than young mice. At 2 d postinfection, aged mice suffered 1000-fold higher pulmonary bacterial burden, 2.2-fold higher levels of neutrophil recruitment to the lung, and a 2.25-fold higher rate of lethal septicemia. Strikingly, α-Toc supplementation of aged mice resulted in a 1000-fold lower bacterial lung burden and full control of infection. This α-Toc–induced resistance to pneumococcal challenge was associated with a 2-fold fewer pulmonary neutrophils, a level comparable to S. pneumoniae–challenged, conventionally fed young mice. α-Toc directly inhibited neutrophil egress across epithelial cell monolayers in vitro in response to pneumococci or hepoxilin-A3, an eicosanoid required for pneumococcus-elicited neutrophil trans-epithelial migration. α-Toc altered expression of multiple epithelial and neutrophil adhesion molecules involved in migration, including CD55, CD47, CD18/CD11b, and ICAM-1. These findings suggest that α-Toc enhances resistance of aged mice to bacterial pneumonia by modulating the innate immune response, a finding that has potential clinical significance in combating infection in aged individuals through nutritional intervention. PMID:25512603

  15. A synthetic review of notoedres species mites and mange

    USGS Publications Warehouse

    Foley, Janet E; Serieys, L.E.; Stephenson, N.; Riley, S.; Foley, C.; Jennings, M.; Wengert, G.; Vickers, W.; Boydston, Erin E.; Lyren, Lisa L.; Moriarty, J.; Clifford, D.L.

    2016-01-01

    Notoedric mange, caused by obligately parasitic sarcoptiform Notoedres mites, is associated with potentially fatal dermatitis with secondary systemic disease in small mammals, felids and procyonids among others, as well as an occasional zoonosis. We describe clinical spectra in non-chiropteran hosts, review risk factors and summarize ecological and epidemiological studies. The genus is disproportionately represented on rodents. Disease in felids and procyonids ranges from very mild to death. Knowledge of the geographical distribution of the mites is highly inadequate, with focal hot spots known for Notoedres cati in domestic cats and bobcats. Predisposing genetic and immunological factors are not known, except that co-infection with other parasites and anticoagulant rodenticide toxicoses may contribute to severe disease. Treatment of individual animals is typically successful with macrocytic lactones such as selamectin, but herd or wildlife population treatment has not been undertaken. Transmission requires close contact and typically is within a host species. Notoedric mange can kill half all individuals in a population and regulate host population below non-diseased density for decades, consistent with frequency-dependent transmission or spillover from other hosts. Epidemics are increasingly identified in various hosts, suggesting global change in suitable environmental conditions or increased reporting bias.

  16. Immunization of rabbits with nematode Ascaris lumbricoides antigens induces antibodies cross-reactive to house dust mite Dermatophagoides farinae antigens.

    PubMed

    Nakazawa, Takuya; Khan, Al Fazal; Yasueda, Hiroshi; Saito, Akemi; Fukutomi, Yuma; Takai, Toshiro; Zaman, Khalequz; Yunus, Md; Takeuchi, Haruko; Iwata, Tsutomu; Akiyama, Kazuo

    2013-01-01

    There are controversial reports on the relationship between helminthic infection and allergic diseases. Although IgE cross-reactivity between nematode Ascaris antigens and house dust-mite allergens in allergic patients have been reported, whether Ascaris or the mite is the primary sensitizer remains unknown. Here we found that immunization of naïve animals with Ascaris lumbricoides (Al) antigens induced production of antibodies cross-reactive to mite antigens from Dermatophagoides farinae (Df). Sera from Bangladeshi children showed IgE reactivity to Ascaris and mite extracts. IgG from rabbits immunized with Al extract exhibited reactivity to Df antigens. Treatment of the anti-Al antibody with Df antigen-coupled beads eliminated the reactivity to Df antigens. In immunoblot analysis, an approximately 100-kDa Df band was the most reactive to anti-Al IgG. The present study is the first step towards the establishment of animal models to study the relationship between Ascaris infection and mite-induced allergic diseases.

  17. Disseminated Mycobacterium genavense infection in a FIV-positive cat.

    PubMed

    Hughes, M S; Ball, N W; Love, D N; Canfield, P J; Wigney, D I; Dawson, D; Davis, P E; Malik, R

    1999-03-01

    An 8-year-old FIV-positive Australian cat was presented with coughing, periocular alopecia, pyrexia and inappetence. Skin scrapings demonstrated Demodex cati mites. Antibiotics were administered and it was treated successfully for periocular demodectic mange, but the cat continued to exhibit respiratory signs and lose weight. Further investigation revealed an ascarid infection and active chronic inflammation of undetected cause affecting the lower airways. Repetitive treatment with pyrantel failed to eradicate the ascarid infection. The cat became cachectic and developed moist ulcerative dermatitis of the neck, severe non-regenerative anaemia, leucopenia and thrombocytopenia. Necropsy and histopathology revealed mycobacteriosis affecting skin, lungs, spleen, lymph nodes, liver and kidney. Attempted culture of frozen tissues at a mycobacteria reference laboratory was unsuccessful. Paraffin-embedded, formalin-fixed tissue was retrieved and examined using PCR to amplify part of the 16S rRNA gene. A diagnosis of disseminated Mycobacterium genavense infection was made based on the presence of acid fast bacteria in many tissues and partial sequence of the 16S rRNA gene. Although M genavense has been identified previously as a cause of disseminated disease in AIDS patients, this is the first report of infection in a cat. It was suspected that the demodecosis, recurrent ascarid infections and disseminated M genavense infection resulted from an immune deficiency syndrome consequent to longstanding FIV infection.

  18. Does the removal of mite-infested brood facilitate grooming?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The relationship between the removal of mite-infested brood and mite drop was compared using Russian (RHB, n = 9) and Italian (IHB, n = 9) honey bee colonies. A cloake board was used to isolate test brood frame on the top hive body and the metal sheet served as a varroa trap. Inoculum mites were col...

  19. Mucoid Pseudomonas aeruginosa isolates maintain the biofilm formation capacity and the gene expression profiles during the chronic lung infection of CF patients.

    PubMed

    Lee, Baoleri; Schjerling, Charlotte K; Kirkby, Nikolai; Hoffmann, Nadine; Borup, Rehannah; Molin, Søren; Høiby, Niels; Ciofu, Oana

    2011-04-01

    Phenotypic and genotypic diversifications of Pseudomonas aeruginosa in the airways of patients with cystic fibrosis (CF) promote long-term survival of bacteria during chronic lung infection. Twelve clonally related, sequential mucoid and non-mucoid paired P. aeruginosa isolates obtained from three Danish CF patients were investigated. The in vitro biofilm formation capacity was studied under static and flow through conditions and the global gene expression profiles were investigated by Affymetrix GeneChip. Regulatory genes of alginate production and quorum sensing (QS) system were sequenced and measurements of the alginate production and the detection of the QS signal molecules were performed. Comparisons of mucoid and non-mucoid isolates from early and late stages of the infection showed that the mucoid phenotype maintained over a decade the capacity to form in vitro biofilm and showed an unaltered transcriptional profile, whereas substantial alterations in the transcriptional profiles and loss of the capacity to form in vitro biofilms were observed in corresponding isolates of the non-mucoid phenotype. The conserved gene expression pattern in the mucoid isolates vs the diversity of changes in non-mucoid isolates observed in this particular P. aeruginosa clone reflects different adaptation strategies used by these two phenotypes in the different niches of the CF lung environment. PMID:21492226

  20. Production of extracellular traps against Aspergillus fumigatus in vitro and in infected lung tissue is dependent on invading neutrophils and influenced by hydrophobin RodA.

    PubMed

    Bruns, Sandra; Kniemeyer, Olaf; Hasenberg, Mike; Aimanianda, Vishukumar; Nietzsche, Sandor; Thywissen, Andreas; Jeron, Andreas; Latgé, Jean-Paul; Brakhage, Axel A; Gunzer, Matthias

    2010-04-29

    Aspergillus fumigatus is the most important airborne fungal pathogen causing life-threatening infections in immunocompromised patients. Macrophages and neutrophils are known to kill conidia, whereas hyphae are killed mainly by neutrophils. Since hyphae are too large to be engulfed, neutrophils possess an array of extracellular killing mechanisms including the formation of neutrophil extracellular traps (NETs) consisting of nuclear DNA decorated with fungicidal proteins. However, until now NET formation in response to A. fumigatus has only been demonstrated in vitro, the importance of neutrophils for their production in vivo is unclear and the molecular mechanisms of the fungus to defend against NET formation are unknown. Here, we show that human neutrophils produce NETs in vitro when encountering A. fumigatus. In time-lapse movies NET production was a highly dynamic process which, however, was only exhibited by a sub-population of cells. NETosis was maximal against hyphae, but reduced against resting and swollen conidia. In a newly developed mouse model we could then demonstrate the existence and measure the kinetics of NET formation in vivo by 2-photon microscopy of Aspergillus-infected lungs. We also observed the enormous dynamics of neutrophils within the lung and their ability to interact with and phagocytose fungal elements in situ. Furthermore, systemic neutrophil depletion in mice almost completely inhibited NET formation in lungs, thus directly linking the immigration of neutrophils with NET formation in vivo. By using fungal mutants and purified proteins we demonstrate that hydrophobin RodA, a surface protein making conidia immunologically inert, led to reduced NET formation of neutrophils encountering Aspergillus fungal elements. NET-dependent killing of Aspergillus-hyphae could be demonstrated at later time-points, but was only moderate. Thus, these data establish that NET formation occurs in vivo during host defence against A. fumigatus, but suggest

  1. Identification of crinosterol from astigamatid mites.

    PubMed

    Murakami, Kenjiro; Watanabe, Bunta; Nishida, Ritsuo; Mori, Naoki; Kuwahara, Yasumasa

    2007-05-01

    A 24-alkylsterol, crinosterol [(24S)-24-methylcholesta-5,22(E)-dien-3beta-ol] has been isolated from sea-dwelling animals, protists and plants. Here, we identified crinosterol from nine species of mites (Acari). The compound was identified by using (1)H-NMR analysis and GCMS spectral data along with the HPLC retention time by comparing with those of the synthesized compound. As far as we know, this is the first report on the identification of crinosterol from arthropods. Furthermore, after Rhizoglyphus robini were fed on artificial diets with d(3)-methionine, d(2)-crinosterol was detected from the mite's extracts. The incorporation of two deuterium atoms into the sterol indicated that a d(3)-methyl group was introduced into the C24 of the side chain to form crinosterol. Although the details of the biosynthesis of crinosterol remain unknown, the discovery of crinosterol in the mites implies the existence of interesting sterol metabolisms in the animals.

  2. Use of scanning electron microscopy to confirm the identity of tropical rat mite (Ornithonyssus bacoti): the cause of rat mite dermatitis.

    PubMed

    Nath, Anjan Jyoti; Islam, Saidul; Sahu, Samyak

    2016-03-01

    Cutaneous lesions in human patient due to the bite of rat mite Ornithonyssus bacoti are frequently misdiagnosed as allergies, fungal infection, or bacterial infection. Bite lesions in the personnel working in a Laboratory Animal facility which was infested with O. bacoti is reported here along with its therapeutic management. Diagnosis of the parasites obtained from the clothing of the personnel and later from the infested mice colony was based on preliminary light microscopy and confirmed by scanning electron microscopy. The mean length and breadth of adult female mite were 1.13 mm × 0.63 mm. The body is hairy, unsegmented and has four pairs of legs. The gnathostoma has long pointed chelicerae and pedipalp. The dorsal surface has one dorsal shield, and the ventral surface has three shields- sternal, genital and anal shield. Treatment of dermatitis involved antihistaminic drugs for a period of 3-5 days. The skin lesion, characterized by papular erythema, tends to disappear within a period of 4-5 days of antihistaminic treatment. In untreated cases, the lesions disappeared within 7-10 days. Tropical rat mite O. bacoti Hirst, 1931 was identified to be the cause of infestation in the laboratory mice colony of Pasteur Institute of India, Coonoor, Tamil Nadu, predisposing the animal handlers to be temporary host. PMID:27065618

  3. Three-Dimensional Engineered High Fidelity Normal Human Lung Tissue-Like Assemblies (TLA) as Targets for Human Respiratory Virus Infections

    NASA Technical Reports Server (NTRS)

    Goodwin, T. J.; Deatly, A. M.; Suderman, M. T.; Lin, Y.-H.; Chen, W.; Gupta, C. K.; Randolph, V. B.; Udem, S. A.

    2003-01-01

    Unlike traditional two-dimensional (2D) cell cultures, three-dimensional (3D) tissue-like assemblies (TLA) (Goodwin et aI, 1992, 1993, 2000 and Nickerson et aI. , 2001,2002) offer high organ fidelity with the potential to emulate the infective dynamics of viruses and bacteria in vivo. Thus, utilizing NASA micro gravity Rotating Wall Vessel (RWV) technology, in vitro human broncho-epithelial (HBE) TLAs were engineered to mimic in vivo tissue for study of human respiratory viruses. These 3D HBE TLAs were propagated from a human broncho-tracheal cell line with a mesenchymal component (HBTC) as the foundation matrix and either an adult human broncho-epithelial cell (BEAS-2B) or human neonatal epithelial cell (16HBE140-) as the overlying element. Resulting TLAs share several characteristic features with in vivo human respiratory epithelium including tight junctions, desmosomes and cilia (SEM, TEM). The presence of epithelium and specific lung epithelium markers furthers the contention that these HBE cells differentiate into TLAs paralleling in vivo tissues. A time course of infection of these 3D HBE TLAs with human respiratory syncytial virus (hRSV) wild type A2 strain, indicates that virus replication and virus budding are supported and manifested by increasing virus titer and detection of membrane-bound F and G glycoproteins. Infected 3D HBE TLAs remain intact for up to 12 days compared to infected 2D cultures that are destroyed in 2-3 days. Infected cells show an increased vacuolation and cellular destruction (by transmission electron microscopy) by day 9; whereas, uninfected cells remain robust and morphologically intact. Therefore, the 3D HBE TLAs mimic aspects of human respiratory epithelium providing a unique opportunity to analyze, for the first time, simulated in vivo viral infection independent of host immune response.

  4. A Study on the Nature of Association between Demodex Mites and Bacteria Involved in Skin and Meibomian Gland Lesions of Demodectic Mange in Cattle

    PubMed Central

    Abu-Samra, Mukhtar Taha; Shuaib, Yassir Adam

    2014-01-01

    The nature of association between Demodex mites and bacteria involved in bovine demodectic mange lesions and the normal flora inhabiting the skin of noninfected animals was investigated. Demodex bovis and D. ghanensis mites were isolated from the infected purulent material extracted from skin and meibomian gland lesions, respectively. The mites could not be demonstrated in skin brushings or impression smears from the eyes of noninfected cattle. Pathogenic bacteria (Staphylococcus aureus and Streptococcus pyogenes (Group A)) and opportunistic organisms (Proteus vulgaris, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Trueperella pyogenes) were isolated from skin lesions of demodectic mange, and Moraxella bovis and Staphylococcus aureus were isolated from meibomian gland lesions. Bacillus subtilis, Escherichia coli, Proteus vulgaris, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus pyogenes (Group A) were isolated from skin brushings from noninfected cattle. The nature of association between Demodex mites and bacteria in demodectic mange lesions is synergistic and of equal significance. Pathogenic and opportunistic bacteria facilitated the establishment of Demodex mites in the lesions produced and provided an excellent microclimate for the mites to propagate and reproduce, resulting in severe and progressive disease. The “high-turnover” granulomatous reaction which characterized the histopathological changes proved that Demodex mites and associated bacteria were persistent and immunogenic. PMID:25177514

  5. CCL20 and Beta-Defensin 2 Production by Human Lung Epithelial Cells and Macrophages in Response to Brucella abortus Infection.

    PubMed

    Hielpos, M Soledad; Ferrero, Mariana C; Fernández, Andrea G; Bonetto, Josefina; Giambartolomei, Guillermo H; Fossati, Carlos A; Baldi, Pablo C

    2015-01-01

    Both CCL20 and human β-defensin 2 (hBD2) interact with the same membrane receptor and display chemotactic and antimicrobial activities. They are produced by airway epithelia in response to infectious agents and proinflammatory cytokines. Whereas Brucella spp. can infect humans through inhalation, their ability to induce CCL20 and hBD2 in lung cells is unknown. Here we show that B. abortus induces CCL20 expression in human alveolar (A549) or bronchial (Calu-6) epithelial cell lines, primary alveolar epithelial cells, primary human monocytes, monocyte-derived macrophages and the monocytic cell line THP-1. CCL20 expression was mainly mediated by JNK1/2 and NF-kB in both Calu-6 and THP-1 cells. CCL20 secretion was markedly induced in A549, Calu-6 and THP-1 cells by heat-killed B. abortus or a model Brucella lipoprotein (L-Omp19) but not by the B. abortus lipopolysaccharide (LPS). Accordingly, CCL20 production by B. abortus-infected cells was strongly TLR2-dependent. Whereas hBD2 expression was not induced by B. abortus infection, it was significantly induced in A549 cells by conditioned media from B. abortus-infected THP-1 monocytes (CMB). A similar inducing effect was observed on CCL20 secretion. Experiments using blocking agents revealed that IL-1β, but not TNF-α, was involved in the induction of hBD2 and CCL20 secretion by CMB. In the in vitro antimicrobial assay, the lethal dose (LD) 50 of CCL20 for B. abortus (>50 μg/ml) was markedly higher than that against E. coli (1.5 μg/ml) or a B. abortus mutant lacking the O polysaccharide in its LPS (8.7 ug/ml). hBD2 did not kill any of the B. abortus strains at the tested concentrations. These results show that human lung epithelial cells secrete CCL20 and hBD2 in response to B. abortus and/or to cytokines produced by infected monocytes. Whereas these molecules do not seem to exert antimicrobial activity against this pathogen, they could recruit immune cells to the infection site.

  6. CCL20 and Beta-Defensin 2 Production by Human Lung Epithelial Cells and Macrophages in Response to Brucella abortus Infection.

    PubMed

    Hielpos, M Soledad; Ferrero, Mariana C; Fernández, Andrea G; Bonetto, Josefina; Giambartolomei, Guillermo H; Fossati, Carlos A; Baldi, Pablo C

    2015-01-01

    Both CCL20 and human β-defensin 2 (hBD2) interact with the same membrane receptor and display chemotactic and antimicrobial activities. They are produced by airway epithelia in response to infectious agents and proinflammatory cytokines. Whereas Brucella spp. can infect humans through inhalation, their ability to induce CCL20 and hBD2 in lung cells is unknown. Here we show that B. abortus induces CCL20 expression in human alveolar (A549) or bronchial (Calu-6) epithelial cell lines, primary alveolar epithelial cells, primary human monocytes, monocyte-derived macrophages and the monocytic cell line THP-1. CCL20 expression was mainly mediated by JNK1/2 and NF-kB in both Calu-6 and THP-1 cells. CCL20 secretion was markedly induced in A549, Calu-6 and THP-1 cells by heat-killed B. abortus or a model Brucella lipoprotein (L-Omp19) but not by the B. abortus lipopolysaccharide (LPS). Accordingly, CCL20 production by B. abortus-infected cells was strongly TLR2-dependent. Whereas hBD2 expression was not induced by B. abortus infection, it was significantly induced in A549 cells by conditioned media from B. abortus-infected THP-1 monocytes (CMB). A similar inducing effect was observed on CCL20 secretion. Experiments using blocking agents revealed that IL-1β, but not TNF-α, was involved in the induction of hBD2 and CCL20 secretion by CMB. In the in vitro antimicrobial assay, the lethal dose (LD) 50 of CCL20 for B. abortus (>50 μg/ml) was markedly higher than that against E. coli (1.5 μg/ml) or a B. abortus mutant lacking the O polysaccharide in its LPS (8.7 ug/ml). hBD2 did not kill any of the B. abortus strains at the tested concentrations. These results show that human lung epithelial cells secrete CCL20 and hBD2 in response to B. abortus and/or to cytokines produced by infected monocytes. Whereas these molecules do not seem to exert antimicrobial activity against this pathogen, they could recruit immune cells to the infection site. PMID:26448160

  7. CCL20 and Beta-Defensin 2 Production by Human Lung Epithelial Cells and Macrophages in Response to Brucella abortus Infection

    PubMed Central

    Fernández, Andrea G.; Bonetto, Josefina; Giambartolomei, Guillermo H.; Fossati, Carlos A.; Baldi, Pablo C.

    2015-01-01

    Both CCL20 and human β-defensin 2 (hBD2) interact with the same membrane receptor and display chemotactic and antimicrobial activities. They are produced by airway epithelia in response to infectious agents and proinflammatory cytokines. Whereas Brucella spp. can infect humans through inhalation, their ability to induce CCL20 and hBD2 in lung cells is unknown. Here we show that B. abortus induces CCL20 expression in human alveolar (A549) or bronchial (Calu-6) epithelial cell lines, primary alveolar epithelial cells, primary human monocytes, monocyte-derived macrophages and the monocytic cell line THP-1. CCL20 expression was mainly mediated by JNK1/2 and NF-kB in both Calu-6 and THP-1 cells. CCL20 secretion was markedly induced in A549, Calu-6 and THP-1 cells by heat-killed B. abortus or a model Brucella lipoprotein (L-Omp19) but not by the B. abortus lipopolysaccharide (LPS). Accordingly, CCL20 production by B. abortus-infected cells was strongly TLR2-dependent. Whereas hBD2 expression was not induced by B. abortus infection, it was significantly induced in A549 cells by conditioned media from B. abortus-infected THP-1 monocytes (CMB). A similar inducing effect was observed on CCL20 secretion. Experiments using blocking agents revealed that IL-1β, but not TNF-α, was involved in the induction of hBD2 and CCL20 secretion by CMB. In the in vitro antimicrobial assay, the lethal dose (LD) 50 of CCL20 for B. abortus (>50 μg/ml) was markedly higher than that against E. coli (1.5 μg/ml) or a B. abortus mutant lacking the O polysaccharide in its LPS (8.7 ug/ml). hBD2 did not kill any of the B. abortus strains at the tested concentrations. These results show that human lung epithelial cells secrete CCL20 and hBD2 in response to B. abortus and/or to cytokines produced by infected monocytes. Whereas these molecules do not seem to exert antimicrobial activity against this pathogen, they could recruit immune cells to the infection site. PMID:26448160

  8. Acaricidal activity of petroleum ether extracts from Eupatorium adenophorum against the ectoparasitic cattle mite, Chorioptes texanus.

    PubMed

    Nong, Xiang; Li, Shu-Hua; Wang, Jia-Hai; Xie, Yue; Chen, Feng-Zheng; Liu, Tian-Fei; He, Ran; Gu, Xiao-Bin; Peng, Xue-Rong; Yang, Guang-You

    2014-03-01

    In this study, we evaluated the acaricidal efficacy of extracts obtained from the plant Eupatorium adenophorum against the common cattle mite Chorioptes texanus. The results showed that 95% ethanol extracts at concentrations of 1.0, 0.5, and 0.25 g/mL (w/v) were highly toxic to C. texanus in vitro, killing 100% of mites in 4 h. Similarly, petroleum ether extracts of E. adenophorum resulted in between 80 and 100% mortality of mites in vitro at concentrations of 0.1, 0.05, and 0.025 mL/mL (v/v) within 4 h. In clinical trials, all infected individuals completely recovered after two treatments administered at 7-day intervals and remained disease-free at 60 days posttreatment. The clinical effect of treatment with E. adenophorum petroleum ether extracts was similar to that of treatment with the acaricide fenvalerate. These results indicated that E. adenophorum contains novel potential acaricidal compounds that can effectively control mites in livestock.

  9. Abscess in the Lungs

    MedlinePlus

    ... abscesses are streptococci and staphylococci, including methicillin-resistant Staphylococcus aureus (MRSA), which is a serious infection. Obstruction ... night sweats. In contrast, lung abscesses caused by Staphylococcus aureus or MRSA can be fatal within days, ...

  10. Lung gallium scan

    MedlinePlus

    ... inflammation in the lungs, most often due to sarcoidosis or a certain type of pneumonia. Normal Results ... up very little gallium. What Abnormal Results Mean Sarcoidosis Other respiratory infections, most often pneumocystis jirovecii pneumonia ...

  11. [Foci of the rat mite Ornithonyssus bacoti (Mesostigmata, Macronyssidae) and rat-mite dermatitis in Moscow].

    PubMed

    Lopatina, Iu V; Sokolova, T V; Niiazova, M V

    1992-01-01

    High density of the rat population in Moscow in 1990-1991 resulted in the appearance of Ornithonyssus bacoti foci and of cases of the rat-mite dermatitis in humans. A total of 36 foci of the disease were examined and eradicated. A method for the detection of such foci has been developed. Two types of foci are distinguished, communal and industrial, and their specific features as regards the rodent and mite populations and clinical features of dermatitis in humans are described. A system of measures for liquidation of foci of rat mites is suggested, including rat and mite eradication and treatment of the patients. Specific features of these measures for various types of foci and in case of a focus reappearance are enumerated. PMID:1299760

  12. [House-dust mites as vectors of human diseases].

    PubMed

    Hoffmann, G

    1982-01-01

    The genuine European house-dust mite, Dermatophagoides pteronyssinus, is the producer of the most common and most potent allergen in the house-dust in Central Europe. Such allergens causing asthma, rhinitis, tracheitis, bronchitis and/or conjunctivitis in man may also be produced by the other species of house-dust mites such as D. farinae and Euroglyphus maynei. House mites and mites of stored products rarely account for such diseases but more frequently for acarodermatitis--especially on farms. Allergies due to house-dust mites mainly occur in midsummer and in early autumn. Particularly children under 10 years of age are effected by these allergies. Textile articles such as mattresses, upholstered furniture and carpets are breeding places of the genuine house-dust mites. Skin scales of humans, mammals and birds affected by mould provide the nutritional substrate of the mites.

  13. Tropical rat mites (Ornithonyssus bacoti) - serious ectoparasites.

    PubMed

    Beck, Wieland; Fölster-Holst, Regina

    2009-08-01

    In Germany there is limited information available about the distribution of the tropical rat mite (Ornithonyssus bacoti) in rodents. A few case reports show that this hematophagous mite species may also cause dermatitis in man. Having close body contact to small rodents is an important question for patients with pruritic dermatoses. The definitive diagnosis of this ectoparasitosis requires the detection of the parasite, which is more likely to be found in the environment of its host (in the cages, in the litter or in corners or cracks of the living area) than on the hosts' skin itself. A case of infestation with tropical rat mites in a family is reported here. Three mice that had been removed from the home two months before were the reservoir. The mites were detected in a room where the cage with the mice had been placed months ago. Treatment requires the eradication of the parasites on its hosts (by a veterinarian) and in the environment (by an exterminator) with adequate acaricides such as permethrin. PMID:19508683

  14. Hold your breath beetle-Mites!

    PubMed

    Gudowska, Agnieszka; Drobniak, Szymon M; Schramm, Bartosz W; Labecka, Anna Maria; Kozlowski, Jan; Bauchinger, Ulf

    2016-01-01

    Respiratory gas exchange in insects occurs via a branching tracheal system. The entrances to the air-filled tracheae are the spiracles, which are gate-like structures in the exoskeleton. The open or closed state of spiracles defines the three possible gas exchange patterns of insects. In resting insects, spiracles may open and close over time in a repeatable fashion that results in a discontinuous gas exchange (DGE) pattern characterized by periods of zero organism-to-environment gas exchange. Several adaptive hypotheses have been proposed to explain why insects engage in DGE, but none have attracted overwhelming support. We provide support for a previously untested hypothesis that posits that DGE minimizes the risk of infestation of the tracheal system by mites and other agents. Here, we analyze the respiratory patterns of 15 species of ground beetle (Carabidae), of which more than 40% of individuals harbored external mites. Compared with mite-free individuals, infested one's engaged significantly more often in DGE. Mite-free individuals predominantly employed a cyclic or continuous gas exchange pattern, which did not include complete spiracle closure. Complete spiracle closure may prevent parasites from invading, clogging, or transferring pathogens to the tracheal system or from foraging on tissue not protected by thick chitinous layers.

  15. Standard methods for tracheal mite research

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This chapter, for the COLOSS Beebook from the Bee Research Center in Switzerland, summarizes all the current information about the tracheal mite (Acarapis woodi) infesting honey bees (Apis mellifera). The chapter covers the effects on bees, its life history, and its range, as well as the identifica...

  16. Understanding PRRSV Infection in Porcine Lung Based on Genome-Wide Transcriptome Response Identified by Deep Sequencing

    PubMed Central

    Xiao, Shuqi; Jia, Jianyu; Mo, Delin; Wang, Qiwei; Qin, Limei; He, Zuyong; Zhao, Xiao; Huang, Yuankai; Li, Anning; Yu, Jingwei; Niu, Yuna; Liu, Xiaohong; Chen, Yaosheng

    2010-01-01

    Porcine reproductive and respiratory syndrome (PRRS) has been one of the most economically important diseases affecting swine industry worldwide and causes great economic losses each year. PRRS virus (PRRSV) replicates mainly in porcine alveolar macrophages (PAMs) and dendritic cells (DCs) and develops persistent infections, antibody-dependent enhancement (ADE), interstitial pneumonia and immunosuppression. But the molecular mechanisms of PRRSV infection still are poorly understood. Here we report on the first genome-wide host transcriptional responses to classical North American type PRRSV (N-PRRSV) strain CH 1a infection using Solexa/Illumina's digital gene expression (DGE) system, a tag-based high-throughput transcriptome sequencing method, and analyse systematically the relationship between pulmonary gene expression profiles after N-PRRSV infection and infection pathology. Our results suggest that N-PRRSV appeared to utilize multiple strategies for its replication and spread in infected pigs, including subverting host innate immune response, inducing an anti-apoptotic and anti-inflammatory state as well as developing ADE. Upregulation expression of virus-induced pro-inflammatory cytokines, chemokines, adhesion molecules and inflammatory enzymes and inflammatory cells, antibodies, complement activation were likely to result in the development of inflammatory responses during N-PRRSV infection processes. N-PRRSV-induced immunosuppression might be mediated by apoptosis of infected cells, which caused depletion of immune cells and induced an anti-inflammatory cytokine response in which they were unable to eradicate the primary infection. Our systems analysis will benefit for better understanding the molecular pathogenesis of N-PRRSV infection, developing novel antiviral therapies and identifying genetic components for swine resistance/susceptibility to PRRS. PMID:20614006

  17. The evolution of size of the uropygial gland: mutualistic feather mites and uropygial secretion reduce bacterial loads of eggshells and hatching failures of European birds.

    PubMed

    Soler, J J; Peralta-Sánchez, J M; Martín-Platero, A M; Martín-Vivaldi, M; Martínez-Bueno, M; Møller, A P

    2012-09-01

    Potentially, pathogenic bacteria are one of the main infective agents against which a battery of chemical and physical barriers has evolved in animals. Among these are the secretions by the exocrine uropygial gland in birds. The antimicrobial properties of uropygial secretions may prevent colonization and growth of microorganisms on feathers, skin and eggshells. However, uropygial gland secretions also favour the proliferation of feather mites that feed on secretions and microorganisms living on feathers that would otherwise reach eggshells during incubation if not consumed by feather mites. Therefore, at the interspecific level, uropygial gland size (as an index of volume of uropygial secretion) should be positively related to eggshell bacterial load (i.e. the risk of egg infection), whereas eggshell bacterial loads may be negatively related to abundance of feather mites eating bacteria. Here, we explore these previously untested predictions in a comparative framework using information on eggshell bacterial loads, uropygial gland size, diversity and abundance of feather mites and hatching success of 22 species of birds. The size of the uropygial gland was positively related to eggshell bacterial loads (mesophilic bacteria and Enterobacteriaceae), and bird species with higher diversity and abundance of feather mites harboured lower bacterial density on their eggshells (Enterococcus and Staphylococcus), in accordance with the hypothesis. Importantly, eggshell bacterial loads of mesophilic bacteria, Enterococcus and Enterobacteriaceae were negatively associated with hatching success, allowing us to interpret these interspecific relationships in a functional scenario, where both uropygial glands and mutualistic feather mites independently reduce the negative effects of pathogenic bacteria on avian fitness.

  18. Probable Phaeoacremonium parasiticum as a cause of cavitary native lung nodules after single lung transplantation.

    PubMed

    Shah, S K; Parto, P; Lombard, G A; James, M A; Beckles, D L; Lick, S; Valentine, V G

    2013-02-01

    Lung nodules after lung transplantation most often represent infection or post-transplant lymphoproliferative disorder in the allograft. Conversely, native lung nodules in single lung transplant recipients are more likely to be bronchogenic carcinoma. We present a patient who developed native lung cavitary nodules. Although malignancy was anticipated, evaluation revealed probable Phaeoacremonium parasiticum infection. Phaeoacremonium parasiticum is a dematiaceous fungus first described as a cause of soft tissue infection in a renal transplant patient. Lung nodules have not been previously described and this is the first case, to our knowledge, of P. parasiticum identified after lung transplantation.

  19. Probable Phaeoacremonium parasiticum as a cause of cavitary native lung nodules after single lung transplantation.

    PubMed

    Shah, S K; Parto, P; Lombard, G A; James, M A; Beckles, D L; Lick, S; Valentine, V G

    2013-02-01

    Lung nodules after lung transplantation most often represent infection or post-transplant lymphoproliferative disorder in the allograft. Conversely, native lung nodules in single lung transplant recipients are more likely to be bronchogenic carcinoma. We present a patient who developed native lung cavitary nodules. Although malignancy was anticipated, evaluation revealed probable Phaeoacremonium parasiticum infection. Phaeoacremonium parasiticum is a dematiaceous fungus first described as a cause of soft tissue infection in a renal transplant patient. Lung nodules have not been previously described and this is the first case, to our knowledge, of P. parasiticum identified after lung transplantation. PMID:23279754

  20. Population survey of phytoseiid mites and spider mites on peach leaves and wild plants in Japanese peach orchard.

    PubMed

    Wari, David; Yamashita, Jun; Kataoka, Yoko; Kohara, Yoko; Hinomoto, Norihide; Kishimoto, Hidenari; Toyoshima, Shingo; Sonoda, Shoji

    2014-07-01

    A population survey of phytoseiid mites and spider mites was conducted on peach leaves and wild plants in Japanese peach orchards having different pesticide practices. The phytoseiid mite species composition on peach leaves and wild plants, as estimated using quantitative sequencing, changed during the survey period. Moreover, it varied among study sites. The phytoseiid mite species compositions were similar between peach leaves and some wild plants, such as Veronica persica, Paederia foetida, Persicaria longiseta, and Oxalis corniculata with larger quantities of phytoseiid mites, especially after mid-summer. A PCR-based method to detect the ribosomal ITS sequences of Tetranychus kanzawai and Panonychus mori from phytoseiid mites was developed. Results showed that Euseius sojaensis (specialized pollen feeder/generalist predator) uses both spider mites as prey in the field.

  1. Dynamics of the phagocytic cell response within the lungs of parabiotic mice infected with mycobacteria with decreasing virulence for mice

    SciTech Connect

    Collins, F.M. )

    1990-07-01

    Alveolar macrophages constitute the first line of defense against an aerogenic mycobacterial challenge. The kinetics of the alveolar macrophage response to an infectious stimulus was studied in parabiotic C57BL/6 x DBA/2 (B6D2)F1 hybrid mice pulse-labeled with tritiated thymidine given to one (donor) animal while the other (recipient) received an equivalent amount of cold thymidine. Lavage fluid collected from uninfected recipients yielded few labeled monocytes. However, after introduction of 10(5) viable Mycobacterium bovis BCG into the lung, an immediate influx of heavily labeled mononuclear cells was observed, peaking around day 3. This cellular response was compared with that induced by several members of the Mycobacterium avium complex of different virulence to mice. The strains M. avium 724 and M. intracellulare 1405, virulent to mice, induced moderate mononuclear cell responses, whereas the avirulent M. intracellulare 1411 induced a predominantly polymorphonuclear rather than mononuclear cell influx, analogous to that seen when heat-killed mycobacteria were introduced into the lung. These results suggest that the mycobacteria within the lung must remain in a metabolically active state in order to induce the maximum mononuclear cell response of the type associated with acquired antituberculous immunity.

  2. Lung-resident eosinophils represent a distinct regulatory eosinophil subset.

    PubMed

    Mesnil, Claire; Raulier, Stéfanie; Paulissen, Geneviève; Xiao, Xue; Birrell, Mark A; Pirottin, Dimitri; Janss, Thibaut; Starkl, Philipp; Ramery, Eve; Henket, Monique; Schleich, Florence N; Radermecker, Marc; Thielemans, Kris; Gillet, Laurent; Thiry, Marc; Belvisi, Maria G; Louis, Renaud; Desmet, Christophe; Marichal, Thomas; Bureau, Fabrice

    2016-09-01

    Increases in eosinophil numbers are associated with infection and allergic diseases, including asthma, but there is also evidence that eosinophils contribute to homeostatic immune processes. In mice, the normal lung contains resident eosinophils (rEos), but their function has not been characterized. Here, we have reported that steady-state pulmonary rEos are IL-5-independent parenchymal Siglec-FintCD62L+CD101lo cells with a ring-shaped nucleus. During house dust mite-induced airway allergy, rEos features remained unchanged, and rEos were accompanied by recruited inflammatory eosinophils (iEos), which were defined as IL-5-dependent peribronchial Siglec-FhiCD62L-CD101hi cells with a segmented nucleus. Gene expression analyses revealed a more regulatory profile for rEos than for iEos, and correspondingly, mice lacking lung rEos showed an increase in Th2 cell responses to inhaled allergens. Such elevation of Th2 responses was linked to the ability of rEos, but not iEos, to inhibit the maturation, and therefore the pro-Th2 function, of allergen-loaded DCs. Finally, we determined that the parenchymal rEos found in nonasthmatic human lungs (Siglec-8+CD62L+IL-3Rlo cells) were phenotypically distinct from the iEos isolated from the sputa of eosinophilic asthmatic patients (Siglec-8+CD62LloIL-3Rhi cells), suggesting that our findings in mice are relevant to humans. In conclusion, our data define lung rEos as a distinct eosinophil subset with key homeostatic functions. PMID:27548519

  3. Infection.

    PubMed

    Saigal, Gaurav; Nagornaya, Natalya; Post, M Judith D

    2016-01-01

    Imaging is useful in the diagnosis and management of infections of the central nervous system. Typically, imaging findings at the outset of the disease are subtle and nonspecific, but they often evolve to more definite imaging patterns in a few days, with less rapidity than for stroke but faster than for neoplastic lesions. This timing is similar to that of noninfectious inflammatory brain disease, such as multiple sclerosis. Fortunately, imaging patterns help to distinguish the two kinds of processes. Other than for sarcoidosis, the meninges are seldom involved in noninfectious inflammation; in contrast, many infectious processes involve the meninges, which then enhance with contrast on computed tomography (CT) or magnetic resonance imaging (MRI). However, brain infection causes a vast array of imaging patterns. Although CT is useful when hemorrhage or calcification is suspected or bony detail needs to be determined, MRI is the imaging modality of choice in the investigation of intracranial infections. Imaging sequences such as diffusion-weighted imaging help in accurately depicting the location and characterizing pyogenic infections and are particularly useful in differentiating bacterial infections from other etiologies. Susceptibility-weighted imaging is extremely useful for the detection of hemorrhage. Although MR spectroscopy findings can frequently be nonspecific, certain conditions such as bacterial abscesses show a relatively specific spectral pattern and are useful in diagnosing and constituting immediate therapy. In this chapter we review first the imaging patterns associated with involvement of various brain structures, such as the epidural and subdural spaces, the meninges, the brain parenchyma, and the ventricles. Involvement of these regions is illustrated with bacterial infections. Next we illustrate the patterns associated with viral and prion diseases, followed by mycobacterial and fungal infections, to conclude with a review of imaging findings

  4. Serum, liver, and lung levels of the major extracellular matrix components at the early stage of BCG-induced granulomatosis depending on the infection route.

    PubMed

    Kim, L B; Shkurupy, V A; Putyatina, A N

    2015-01-01

    Experiments on the model of mouse BCG-induced granulomatous showed that the content of glycosaminoglycans and proteoglycans in the extracellular matrix of the liver and lungs are changed at the early stages of inflammation (days 3 and 30 postinfection) before cell destruction in the organs begins. This is related to degradation of extracellular matrix structures. Their high content in the blood and interstitium probably contributes to the formation of granulomas, fibroblast proliferation and organ fibrosis. These processes depend on the infection route that determines different conditions for generalization of the inflammation process. Intravenous method of vaccine injection is preferable to use when designing the experiments simulating tuberculosis granulomatosis, especially for the analysis of its early stages. PMID:25573360

  5. Serum, liver, and lung levels of the major extracellular matrix components at the early stage of BCG-induced granulomatosis depending on the infection route.

    PubMed

    Kim, L B; Shkurupy, V A; Putyatina, A N

    2015-01-01

    Experiments on the model of mouse BCG-induced granulomatous showed that the content of glycosaminoglycans and proteoglycans in the extracellular matrix of the liver and lungs are changed at the early stages of inflammation (days 3 and 30 postinfection) before cell destruction in the organs begins. This is related to degradation of extracellular matrix structures. Their high content in the blood and interstitium probably contributes to the formation of granulomas, fibroblast proliferation and organ fibrosis. These processes depend on the infection route that determines different conditions for generalization of the inflammation process. Intravenous method of vaccine injection is preferable to use when designing the experiments simulating tuberculosis granulomatosis, especially for the analysis of its early stages.

  6. The distribution of dust mite allergen in the houses of patients with asthma

    SciTech Connect

    Tovey, E.R.; Chapman, M.D.; Wells, C.W.; Platts-Mills, T.A.

    1981-11-01

    Using an inhibition radioimmunoassay for the major allergen from Dermatophagoides pteronyssinus (antigen P1), we studied the distribution of this dust allergen in the houses of patients with asthma. Both bed and floor dust samples contained a wide range of antigen P1, 100 to 100,000 ng/g of fine dust, and this concentration correlated well with the number of mite bodies (r . 0.81, p less than 0.001). We were unable to detect antigen P1 in the air of undisturbed rooms. However, during domestic activity, between 1 and 30 ng were collected on a filter than sampled air for 45 min at 17 L/min. Using a cascade impactor it was shown that greater than 80% of the airborne antigen P1 was associated with particles greater than 10 mu in diameter. Some of the particles containing allergen could be identified because they formed precipitin rings when impacted onto agarose containing rabbit antimite antiserum. These particles had the physical appearance of mite feces, which are the major source of antigen P1 in mite cultures. The results suggested that natural exposure to this dust allergen allows occasional fecal particles to enter the lungs and that these particles contain very concentrated allergen.

  7. Accumulation of CD11b⁺Gr-1⁺ cells in the lung, blood and bone marrow of mice infected with highly pathogenic H5N1 and H1N1 influenza viruses.

    PubMed

    Long, James P; Kotur, Mark S; Stark, Gregory V; Warren, Richard L; Kasoji, Manjula; Craft, Jeremy L; Albrecht, Randy A; García-Sastre, Adolfo; Katze, Michael G; Waters, Katrina M; Vasconcelos, Daphne; Sabourin, Patrick J; Bresler, Herbert S; Sabourin, Carol L

    2013-06-01

    Infection with pathogenic influenza viruses is associated with intense inflammatory disease. Here, we investigated the innate immune response in mice infected with H5N1 A/Vietnam/1203/04 and with reassortant human H1N1 A/Texas/36/91 viruses containing the virulence genes hemagglutinin (HA), neuraminidase (NA) and NS1 of the 1918 pandemic virus. Inclusion of the 1918 HA and NA glycoproteins rendered a seasonal H1N1 virus capable of inducing an exacerbated host innate immune response similar to that observed for highly pathogenic A/Vietnam/1203/04 virus. Infection with 1918 HA/NA:Tx/91 and A/Vietnam/1203/04 were associated with severe lung pathology, increased cytokine and chemokine production, and significant immune cell changes, including the presence of CD11b(+)Gr-1(+) cells in the blood, lung and bone marrow. Significant differential gene expression in the lung included pathways for cell death, apoptosis, production and response to reactive oxygen radicals, as well as arginine and proline metabolism and chemokines associated with monocyte and neutrophil/granulocyte accumulation and/or activation. Arginase was produced in the lung of animals infected with A/Vietnam/1204. These results demonstrate that the innate immune cell response results in the accumulation of CD11b(+)Gr-1(+) cells and products that have previously been shown to contribute to T cell suppression.

  8. Depletion of Neutrophils Exacerbates the Early Inflammatory Immune Response in Lungs of Mice Infected with Paracoccidioides brasiliensis

    PubMed Central

    Lopera, Damaris; Urán-Jiménez, Martha Eugenia

    2016-01-01

    Neutrophils predominate during the acute phase of the Paracoccidioides brasiliensis infection. Herein, we determined the role of the neutrophil during the early stages of experimental pulmonary paracoccidioidomycosis using a monoclonal antibody (mAb) specific for neutrophils. Male BALB/c mice were inoculated intranasally with 1.5 × 106 or 2 × 106 P. brasiliensis yeast cells. The mAb was administered 24 h before infection, followed by doses every 48 h until mice were sacrificed. Survival time was evaluated and mice were sacrificed at 48 h and 96 h after inoculation to assess cellularity, fungal load, cytokine/chemokine levels, and histopathological analysis. Neutrophils from mAb-treated mice were efficiently depleted (99.04%). Eighty percent of the mice treated with the mAb and infected with 1.5 × 106 yeast cells died during the first two weeks after infection. When mice were treated and infected with 2 × 106 yeast cells, 100% of them succumbed by the first week after infection. During the acute inflammatory response significant increases in numbers of eosinophils, fungal load and levels of proinflammatory cytokines/chemokines were observed in the mAb-treated mice. We also confirmed that neutrophils are an important source of IFN-γ and IL-17. These results indicate that neutrophils are essential for protection as well as being important for regulating the early inflammatory immune response in experimental pulmonary paracoccidioidomycosis.

  9. Depletion of Neutrophils Exacerbates the Early Inflammatory Immune Response in Lungs of Mice Infected with Paracoccidioides brasiliensis

    PubMed Central

    Lopera, Damaris; Urán-Jiménez, Martha Eugenia

    2016-01-01

    Neutrophils predominate during the acute phase of the Paracoccidioides brasiliensis infection. Herein, we determined the role of the neutrophil during the early stages of experimental pulmonary paracoccidioidomycosis using a monoclonal antibody (mAb) specific for neutrophils. Male BALB/c mice were inoculated intranasally with 1.5 × 106 or 2 × 106 P. brasiliensis yeast cells. The mAb was administered 24 h before infection, followed by doses every 48 h until mice were sacrificed. Survival time was evaluated and mice were sacrificed at 48 h and 96 h after inoculation to assess cellularity, fungal load, cytokine/chemokine levels, and histopathological analysis. Neutrophils from mAb-treated mice were efficiently depleted (99.04%). Eighty percent of the mice treated with the mAb and infected with 1.5 × 106 yeast cells died during the first two weeks after infection. When mice were treated and infected with 2 × 106 yeast cells, 100% of them succumbed by the first week after infection. During the acute inflammatory response significant increases in numbers of eosinophils, fungal load and levels of proinflammatory cytokines/chemokines were observed in the mAb-treated mice. We also confirmed that neutrophils are an important source of IFN-γ and IL-17. These results indicate that neutrophils are essential for protection as well as being important for regulating the early inflammatory immune response in experimental pulmonary paracoccidioidomycosis. PMID:27642235

  10. Broad-spectrum antimicrobial efficacy of peptide A3-APO in mouse models of multidrug-resistant wound and lung infections cannot be explained by in vitro activity against the pathogens involved.

    PubMed

    Ostorhazi, Eszter; Holub, Marianna Csilla; Rozgonyi, Ferenc; Harmos, Ferenc; Cassone, Marco; Wade, John D; Otvos, Laszlo

    2011-05-01

    Although the designer proline-rich antimicrobial peptide A3-APO has only modest activity against Escherichia coli and Acinetobacter baumannii in vitro, in mouse models of systemic and wound infections it shows superior efficacy compared with conventional antibiotics. In this study, the efficacy of A3-APO in several additional mouse models was investigated, including Staphylococcus aureus wound infection, mixed Klebsiella pneumoniae-A. baumannii-Proteus mirabilis wound infection and K. pneumoniae lung infection, mimicking blast wound infections, foot ulcers and ventilator-induced nosocomial infections, respectively. Whilst the peptide practically did not kill the strains in vitro, when administered intramuscularly or as an aerosol it significantly improved mouse survival and reduced bacterial counts at the infection site and in blood. In the lung infection study, the blood bacterial counts following A3-APO treatment were as low as after treatment with colistin and were lower than after treatment with imipenem or amikacin. The wounds of treated animals, unlike their untreated counterparts, lacked pus and signs of inflammation. In human peripheral blood mononuclear cells, A3-APO upregulated the expression of the anti-inflammatory cytokines interleukin-4 and interleukin-10 by four- to six-fold. One of the mechanisms mediating the in vivo protective effects might be the prevention of inflammation around bacterial infiltration.

  11. Influence of inoculum size and marbofloxacin plasma exposure on the amplification of resistant subpopulations of Klebsiella pneumoniae in a rat lung infection model.

    PubMed

    Kesteman, Anne-Sylvie; Ferran, Aude A; Perrin-Guyomard, Agnès; Laurentie, Michel; Sanders, Pascal; Toutain, Pierre-Louis; Bousquet-Mélou, Alain

    2009-11-01

    We tested the hypothesis that the bacterial load at the infection site could impact considerably on the pharmacokinetic/pharmacodynamic (PK/PD) parameters of fluoroquinolones. Using a rat lung infection model, we measured the influence of different marbofloxacin dosage regimens on selection of resistant bacteria after infection with a low (10(5) CFU) or a high (10(9) CFU) inoculum of Klebsiella pneumoniae. For daily fractionated doses of marbofloxacin, prevention of resistance occurred for an area-under-the-concentration-time-curve (AUC)/MIC ratio of 189 h for the low inoculum, whereas for the high inoculum, resistant-subpopulation enrichment occurred for AUC/MIC ratios up to 756 h. For the high-inoculum-infected rats, the AUC/MIC ratio, C(max)/MIC ratio, and time within the mutant selection window (T(MSW)) were not found to be effective predictors of resistance prevention upon comparison of fractionated and single administrations. An index corresponding to the ratio of the time that the drug concentrations were above the mutant prevention concentration (MPC) over the time that the drug concentrations were within the MSW (T(>MPC)/T(MSW)) was the best predictor of the emergence of resistance: a T(>MPC)/T(MSW) ratio of 0.54 was associated with prevention of resistance for both fractionated and single administrations. These results suggest that the enrichment of resistant bacteria depends heavily on the inoculum size at the start of an antimicrobial treatment and that classical PK/PD parameters cannot adequately describe the impact of different dosage regimens on enrichment of resistant bacteria. We propose an original index, the T(>MPC)/T(MSW) ratio, which reflects the ratio of the time that the less susceptible bacterial subpopulation is killed over the time that it is selected, as a potentially powerful indicator of prevention of enrichment of resistant bacteria. This ratio is valid only if plasma concentrations achieve the MPC.

  12. Work-related allergies to storage mites in Parma (Italy) ham workers

    PubMed Central

    Tafuro, Federica; Ridolo, Erminia; Goldoni, Matteo; Montagni, Marcello; Mutti, Antonio; Corradi, Massimo

    2015-01-01

    Objectives To investigate the role of storage mites in the development of allergic diseases among ham production workers, and to search for early alterations in lung function tests and early inflammation markers in exhaled air. Respiratory allergies due to storage mites have been reported in people with various occupations but, although such mites are unavoidable when curing ham, there are no published data concerning ham production workers. Setting Secondary care. Design Experimental cross-sectional study. Participants 220 participants (110 ham production workers and 110 controls) were recruited. Primary and secondary outcome measures Workers answered a medical questionnaire, and underwent spirometry and fraction of exhaled nitric oxide at 50 mL/s (FeNO50) measurements. Those with allergic symptoms also underwent skin prick tests to determine their sensitisation to airborne allergens. A methacholine test was performed in symptomatic participants when spirometry was normal to assess airways hyper-responsiveness. Results Symptomatic storage mite sensitisation was observed in 16 workers (14.5%) (rhinoconjunctivitis in 15 (63%) and asthma in (4%)) and 2 controls (1.8%; p=0.001). Higher FeNO50 values in exposed symptomatic workers compared with healthy control participants (34.65±7.49 vs 13.29±4.29 ppb; p<0.001) suggested bronchial and nasal involvement, although their lung function parameters were normal. Regardless of exposure, a FeNO50 value of 22.5 ppb seems to be 100% sensitive and 99.4% specific in distinguishing allergic and non-allergic participants. Multivariate analysis of FeNO50 values in the symptomatic participants showed that they were positively influenced by IgE-mediated allergy (p=0.001) and reported symptom severity (p=0.041), and negatively by smoking status (p=0.049). Conclusions Ham processing workers, as well as workers involved in any meat processing work that includes curing, should be informed about the occupational risk of

  13. Lung Emergencies

    MedlinePlus

    ... Emergencies Cardiac Emergencies Eye Emergencies Lung Emergencies Surgeries Lung Emergencies People with Marfan syndrome can be at ... should be considered an emergency. Symptoms of sudden lung collapse (pneumothorax) Symptoms of a sudden lung collapse ...

  14. Lung Cancer

    MedlinePlus

    ... version of this page please turn Javascript on. Lung Cancer What is Lung Cancer? How Tumors Form The body is made ... button on your keyboard.) Two Major Types of Lung Cancer There are two major types of lung ...

  15. Lung metastases

    MedlinePlus

    Metastases to the lung; Metastatic cancer to the lung ... Metastatic tumors in the lungs are cancers that developed at other places in the body (or other parts of the lungs) and spread through the ...

  16. Remote sensing to detect the movement of wheat curl mites through the spatial spread of virus symptoms, and identification of thrips as predators of wheat curl mites

    NASA Astrophysics Data System (ADS)

    Stilwell, Abby R.

    The wheat curl mite (WCM), Aceria tosichella Keifer, transmits three viruses to winter wheat: wheat streak mosaic virus, High Plains virus, and Triticum mosaic virus. This virus complex causes yellowing of the foliage and stunting of plants. WCMs disperse by wind, and an increased understanding of mite movement and subsequent virus spread is necessary in determining the risk of serious virus infections in winter wheat. These risk parameters will help growers make better decisions regarding WCM management. The objectives of this study were to evaluate the capabilities of remote sensing to identify virus infected plants and to establish the potential of using remote sensing to track virus spread and consequently, mite movement. Although the WCM is small and very hard to track, the viruses it vectors produce symptoms that can be detected with remote sensing. Field plots of simulated volunteer wheat were established between 2006 and 2009, infested with WCMs, and spread mites and virus into adjacent winter wheat. The virus gradients created by WCM movement allowed for the measurement of mite movement potential with both proximal and aerial remote sensing instruments. The ability to detect WCM-vectored viruses with remote sensing was investigated by comparing vegetation indices calculated from proximal remote sensing data to ground truth data obtained in the field. Of the ten vegetation indices tested, the red edge position (REP) index had the best relationship with ground truth data. The spatial spread of virus from WCM source plots was modeled with cokriging. Virus symptoms predicted by cokriging occurred in an oval pattern displaced to the southeast. Data from the spatial spread in small plots of this study were used to estimate the potential sphere of influence for volunteer wheat fields. The impact of thrips on WCM populations was investigated by a series of greenhouse, field, and observational studies. WCM populations in winter wheat increased more slowly when

  17. A New Species of Chigger Mite (Acari: Trombiculidae) from Rodents in Southwest China

    PubMed Central

    Ren, Tian-Guang; Wu, Dian; Fletcher, Quinn E.

    2014-01-01

    This paper describes a new species of chigger mite (Acari: Trombiculidae), Gahrliepia cangshanensis n. sp., from rodents in southwest China. The specimens were collected from Yunnan red-backed voles, Eothenomys miletus (Thomas, 1914), and a Chinese white-bellied rat, Niviventer confucianus (Milne-Edwards, 1871) in Yunnan Province. The new species is unique mainly in its number of dorsal setae (n=21), and it has the following features: fT (formula of palpotarsus)=4B (B=branched), fp (formula of palpal seta)=B/N/N/N/B (N=naked), a broad tongue-shaped scutum with an almost straight posterior margin, and 17 PPLs (posterior posterolateral seta) with a length of 36-43 µm. This chigger mite may also infect other rodent hosts and may be distributed in other localities. PMID:24623884

  18. Bottom-up regulation of malaria population dynamics in mice co-infected with lung-migratory nematodes.

    PubMed

    Griffiths, Emily C; Fairlie-Clarke, Karen; Allen, Judith E; Metcalf, C Jessica E; Graham, Andrea L

    2015-12-01

    When and how populations are regulated by bottom up vs. top down processes, and how those processes are affected by co-occurring species, are poorly characterised across much of ecology. We are especially interested in the community ecology of parasites that must share a host. Here, we quantify how resources and immunity affect parasite propagation in experiments in near-replicate 'mesocosms'' - i.e. mice infected with malaria (Plasmodium chabaudi) and nematodes (Nippostrongylus brasiliensis). Nematodes suppressed immune responses against malaria, and yet malaria populations were smaller in co-infected hosts. Further analyses of within-host epidemiology revealed that nematode co-infection altered malaria propagation by suppressing target cell availability. This is the first demonstration that bottom-up resource regulation may have earlier and stronger effects than top-down immune mechanisms on within-host community dynamics. Our findings demonstrate the potential power of experimental ecology to disentangle mechanisms of population regulation in complex communities. PMID:26477454

  19. A house dust mite allergen homologue from poultry red mite Dermanyssus gallinae (De Geer).

    PubMed

    Nisbet, A J; Huntley, J F; Mackellar, A; Sparks, N; McDevitt, R

    2006-08-01

    Tropomyosin is an allergenic, actin-binding protein and a proposed vaccine candidate from several species of parasite. Tropomyosin cDNA, obtained by polymerase chain reaction (PCR) amplification from Dermanyssus gallinae RNA, encoded a predicted protein with 89% and 88% identity to tropomyosins from the ticks Boophilus microplus and Haemaphysalis longicornis, respectively, and 85% identity to the house dust mite (HDM) tropomyosin Der p 10. Mouse antibodies raised against HDM tropomyosin reacted with a band of 38 kDa on Western blots of D. gallinae extract, consistent with the molecular masses of acarine tropomyosins and the putative product of the cDNA encoding D. gallinae tropomyosin. When the same preparation of D. gallinae proteins was used in Western blots with serum from infested hens, the IgY component of the serum bound to a number of mite proteins, but not to tropomyosin, indicating that hens are not directly exposed to this allergen during a natural infestation. Immunolocalization of tropomyosin in mites indicated a ubiquitous distribution of the molecule in mite tissues. Immunolocalization and Western blotting also indicated that poultry red mites ingest host IgY.

  20. Salivary proteins of spider mites suppress defenses in Nicotiana benthamiana and promote mite reproduction.

    PubMed

    Villarroel, Carlos A; Jonckheere, Wim; Alba, Juan M; Glas, Joris J; Dermauw, Wannes; Haring, Michel A; Van Leeuwen, Thomas; Schuurink, Robert C; Kant, Merijn R

    2016-04-01

    Spider mites (Tetranychidae sp.) are widely occurring arthropod pests on cultivated plants. Feeding by the two-spotted spider mite T. urticae, a generalist herbivore, induces a defense response in plants that mainly depends on the phytohormones jasmonic acid and salicylic acid (SA). On tomato (Solanum lycopersicum), however, certain genotypes of T. urticae and the specialist species T. evansi were found to suppress these defenses. This phenomenon occurs downstream of phytohormone accumulation via an unknown mechanism. We investigated if spider mites possess effector-like proteins in their saliva that can account for this defense suppression. First we performed an in silico prediction of the T. urticae and the T. evansi secretomes, and subsequently generated a short list of candidate effectors based on additional selection criteria such as life stage-specific expression and salivary gland expression via whole mount in situ hybridization. We picked the top five most promising protein families and then expressed representatives in Nicotiana benthamiana using Agrobacterium tumefaciens transient expression assays to assess their effect on plant defenses. Four proteins from two families suppressed defenses downstream of the phytohormone SA. Furthermore, T. urticae performance on N. benthamiana improved in response to transient expression of three of these proteins and this improvement was similar to that of mites feeding on the tomato SA accumulation mutant nahG. Our results suggest that both generalist and specialist plant-eating mite species are sensitive to SA defenses but secrete proteins via their saliva to reduce the negative effects of these defenses. PMID:26946468

  1. Salivary proteins of spider mites suppress defenses in Nicotiana benthamiana and promote mite reproduction.

    PubMed

    Villarroel, Carlos A; Jonckheere, Wim; Alba, Juan M; Glas, Joris J; Dermauw, Wannes; Haring, Michel A; Van Leeuwen, Thomas; Schuurink, Robert C; Kant, Merijn R

    2016-04-01

    Spider mites (Tetranychidae sp.) are widely occurring arthropod pests on cultivated plants. Feeding by the two-spotted spider mite T. urticae, a generalist herbivore, induces a defense response in plants that mainly depends on the phytohormones jasmonic acid and salicylic acid (SA). On tomato (Solanum lycopersicum), however, certain genotypes of T. urticae and the specialist species T. evansi were found to suppress these defenses. This phenomenon occurs downstream of phytohormone accumulation via an unknown mechanism. We investigated if spider mites possess effector-like proteins in their saliva that can account for this defense suppression. First we performed an in silico prediction of the T. urticae and the T. evansi secretomes, and subsequently generated a short list of candidate effectors based on additional selection criteria such as life stage-specific expression and salivary gland expression via whole mount in situ hybridization. We picked the top five most promising protein families and then expressed representatives in Nicotiana benthamiana using Agrobacterium tumefaciens transient expression assays to assess their effect on plant defenses. Four proteins from two families suppressed defenses downstream of the phytohormone SA. Furthermore, T. urticae performance on N. benthamiana improved in response to transient expression of three of these proteins and this improvement was similar to that of mites feeding on the tomato SA accumulation mutant nahG. Our results suggest that both generalist and specialist plant-eating mite species are sensitive to SA defenses but secrete proteins via their saliva to reduce the negative effects of these defenses.

  2. Depletion of Neutrophils Exacerbates the Early Inflammatory Immune Response in Lungs of Mice Infected with Paracoccidioides brasiliensis.

    PubMed

    Pino-Tamayo, Paula Andrea; Puerta-Arias, Juan David; Lopera, Damaris; Urán-Jiménez, Martha Eugenia; González, Ángel

    2016-01-01

    Neutrophils predominate during the acute phase of the Paracoccidioides brasiliensis infection. Herein, we determined the role of the neutrophil during the early stages of experimental pulmonary paracoccidioidomycosis using a monoclonal antibody (mAb) specific for neutrophils. Male BALB/c mice were inoculated intranasally with 1.5 × 10(6) or 2 × 10(6) P. brasiliensis yeast cells. The mAb was administered 24 h before infection, followed by doses every 48 h until mice were sacrificed. Survival time was evaluated and mice were sacrificed at 48 h and 96 h after inoculation to assess cellularity, fungal load, cytokine/chemokine levels, and histopathological analysis. Neutrophils from mAb-treated mice were efficiently depleted (99.04%). Eighty percent of the mice treated with the mAb and infected with 1.5 × 10(6) yeast cells died during the first two weeks after infection. When mice were treated and infected with 2 × 10(6) yeast cells, 100% of them succumbed by the first week after infection. During the acute inflammatory response significant increases in numbers of eosinophils, fungal load and levels of proinflammatory cytokines/chemokines were observed in the mAb-treated mice. We also confirmed that neutrophils are an important source of IFN-γ and IL-17. These results indicate that neutrophils are essential for protection as well as being important for regulating the early inflammatory immune response in experimental pulmonary paracoccidioidomycosis. PMID:27642235

  3. Lung cancer

    SciTech Connect

    Aisner, J.

    1985-01-01

    This book contains 13 chapters. Some of the chapter titles are: The Pathology of Lung Cancer; Radiotherapy for Non-Small-Cell Cancer of the Lung; Chemotherapy for Non-Small-Cell Lung Cancer; Immunotherapy in the Management of Lung Cancer; Preoperative Staging and Surgery for Non-Small-Cell Lung Cancer; and Prognostic Factors in Lung Cancer.

  4. Diversity of feather mites (Acari: Astigmata) on Darwin's finches.

    PubMed

    Villa, Scott M; Le Bohec, Céline; Koop, Jennifer A H; Proctor, Heather C; Clayton, Dale H

    2013-10-01

    Feather mites are a diverse group of ectosymbionts that occur on most species of birds. Although Darwin's finches are a well-studied group of birds, relatively little is known about their feather mites. Nearly 200 birds across 9 finch species, and from 2 locations on Santa Cruz Island, Galápagos, were dust-ruffled during the 2009 breeding season. We found 8 genera of feather mites; the most prevalent genus was Mesalgoides (53-55%), followed by Trouessartia (40-45%), Amerodectes and Proctophyllodes (26-33%), Xolalgoides (21-27%), Analges and Strelkoviacarus (0-6%), and Dermoglyphus (2-4%). There was no evidence for microclimatic effects (ambient temperature and relative humidity) on mite diversity. Host body mass was significantly correlated with mean feather mite abundance across 7 of 8 well-sampled species of finches. Certhidea olivacea, the smallest species, did not fit this pattern and had a disproportionately high number of mites for its body mass.

  5. Remote sensing of spider mite damage in California peach orchards

    NASA Astrophysics Data System (ADS)

    Luedeling, Eike; Hale, Adam; Zhang, Minghua; Bentley, Walter J.; Dharmasri, L. Cecil

    2009-08-01

    Remote sensing techniques can decrease pest monitoring costs in orchards. To evaluate the feasibility of detecting spider mite damage in orchards, we measured visible and near infrared reflectance of 1153 leaves and 392 canopies in 11 peach orchards in California. Pairs of significant wavelengths, identified by Partial Least Squares regression, were combined into normalized difference indices. These and 9 previously published indices were evaluated for correlation with mite damage. Eight spectral regions for leaves and two regions for canopies (at blue and red wavelengths) were significantly correlated with mite damage. These findings were tested by calculating normalized difference indices from the Red and Blue bands of six multispectral aerial images. Index values were linearly correlated with mite damage ( R2 = 0.47), allowing identification of mite hotspots in orchards. However, better standardization of aerial imagery and accounting for perturbing environmental factors will be necessary for making this technique applicable for early mite detection.

  6. Seasonal phoresy as an overwintering strategy of a phytophagous mite

    PubMed Central

    Liu, Sai; Li, Jianling; Guo, Kun; Qiao, Haili; Xu, Rong; Chen, Jianmin; Xu, Changqing; Chen, Jun

    2016-01-01

    Migration by attachment to insects is common among mites that live in temporary habitats. However, because plants provide relatively stable habitats, phytophagous mites are generally not dependent on other animals for dispersal, so whether these mites can consistently be phoretic on insects through a particular life stage remains unclear and controversial. Here, we describe an obligate phoresy of a wholly phytophagous mite, Aceria pallida, in which the mites accompanied the psyllid Bactericera gobica to its winter hibernation sites, thus successfully escaping unfavourable winter conditions, and returned to reach the buds of their host plant early the following spring. This finding provides evidence of a new overwintering strategy that has contributed to the evolutionary success of these tiny phytophagous mites. PMID:27150196

  7. Seasonal phoresy as an overwintering strategy of a phytophagous mite.

    PubMed

    Liu, Sai; Li, Jianling; Guo, Kun; Qiao, Haili; Xu, Rong; Chen, Jianmin; Xu, Changqing; Chen, Jun

    2016-01-01

    Migration by attachment to insects is common among mites that live in temporary habitats. However, because plants provide relatively stable habitats, phytophagous mites are generally not dependent on other animals for dispersal, so whether these mites can consistently be phoretic on insects through a particular life stage remains unclear and controversial. Here, we describe an obligate phoresy of a wholly phytophagous mite, Aceria pallida, in which the mites accompanied the psyllid Bactericera gobica to its winter hibernation sites, thus successfully escaping unfavourable winter conditions, and returned to reach the buds of their host plant early the following spring. This finding provides evidence of a new overwintering strategy that has contributed to the evolutionary success of these tiny phytophagous mites. PMID:27150196

  8. Intestinal proteases of free-living and parasitic astigmatid mites.

    PubMed

    Holt, Deborah C; Burgess, Stewart T G; Reynolds, Simone L; Mahmood, Wajahat; Fischer, Katja

    2013-02-01

    Among arthropod pests, mites are responsible for considerable damage to crops, humans and other animals. However, detailed physiological data on these organisms remain sparse, mainly because of their small size but possibly also because of their extreme diversity. Focusing on intestinal proteases, we draw together information from three distinct mite species that all feed on skin but have separately adapted to a free-living, a strictly ecto-parasitic and a parasitic lifestyle. A wide range of studies involving immunohistology, molecular biology, X-ray crystallography and enzyme biochemistry of mite gut proteases suggests that these creatures have diverged considerably as house dust mites, sheep scab mites and scabies mites. Each species has evolved a particular variation of a presumably ancestral repertoire of digestive enzymes that have become specifically adapted to their individual environmental requirements.

  9. [Epidemiological Studies On The Acaroid Mite

    PubMed

    Chu, Jung Kyun; Song, Soo Bok; Kim, Don Kyun; Kim, Yeong Kyu

    1967-06-01

    Epidemiological study on Acaroid mite in dust different sites were carried out and the following results were obtained. 1. Tyrophagus dimidiatus, Chibidania tokyoensis and Ornithonyssus nagayoi were found in living room(46.2 %), bath room(36.7 %), garden(27.0 %), shopping-store(28.8 %) and ware-house (29.2 %) in the Pusan area. 2. Dermanyssus gallinae and Rhizoglyphus echinopus were found mainly in class rooms of girl's high school(34.0 %) and class room of girl's middle school(40.0 %) as well as in primary school(13.2 %), but they are not found in class rooms of boys high school. 3. Generally, the various mites were found in the living room(57.0 %), under the carpet(50 %), under the furniture(52.0 %), on the furniture(27.5 %), lavatory(35.7 %) and garden(23.8 %).

  10. Tyrophagus putrescentiae: an allergenically important mite.

    PubMed

    Green, W F; Woolcock, A J

    1978-03-01

    The incidence of positive skin tests to the mite Tyrophagus putrescentiae was measured and compared with skin reactions to Dermatophagoides pteronyssinus and other allergens in Australian and New Guinean populations, and mite counts were determined in Sydney and New Guinea houses. Positive reactions to T. putrescentiae were as frequent as those for D. pteronyssinus in asthmatics in Sydney and were the commonest positive reactions in the normal New Guinea population. T. putrescentiae-specific serum IgE levels were determined and some IgG cross-reactions of D. pteronyssinus and T. putrescentiae antigens were demonstrated. It is suggested that T. putrescentiae is an important source of allergen and should be considered whenever D. pteronyssinus is thought to be a problem. A convenient method for culturing and isolating T. putrescentiae is described. PMID:647897

  11. The Jean Gutierrez spider mite collection.

    PubMed

    Migeon, Alain

    2015-01-01

    The family Tetranychidae (spider mites) currently comprises 1,275 species and represents one of the most important agricultural pest families among the Acari with approximately one hundred pest species, ten of which considered major pests. The dataset presented in this document includes all the identified spider mites composing the Jean Gutierrez Collection hosted at the CBGP (Montferrier-sur-Lez, France), gathered from 1963 to 1999 during his career at the Institut de Recherche pour le Développement (IRD). It consists of 5,262 specimens corresponding to 1,564 occurrences (combination species/host plant/date/location) of 175 species. Most specimens were collected in Madagascar and other islands of the Western Indian Ocean, New Caledonia and other islands of the South Pacific and Papuasia. The dataset constitutes today the most important one available on Tetranychidae worldwide.

  12. Porcine CD3+NKp46+ Lymphocytes Have NK-Cell Characteristics and Are Present in Increased Frequencies in the Lungs of Influenza-Infected Animals

    PubMed Central

    Mair, Kerstin H.; Stadler, Maria; Talker, Stephanie C.; Forberg, Hilde; Storset, Anne K.; Müllebner, Andrea; Duvigneau, J. Catharina; Hammer, Sabine E.; Saalmüller, Armin; Gerner, Wilhelm

    2016-01-01

    The CD3−NKp46+ phenotype is frequently used for the identification of natural killer (NK) cells in various mammalian species. Recently, NKp46 expression was analyzed in more detail in swine. It could be shown that besides CD3−NKp46+ lymphocytes, a small but distinct population of CD3+NKp46+ cells exists. In this study, we report low frequencies of CD3+NKp46+ lymphocytes in blood, lymph nodes, and spleen, but increased frequencies in non-lymphatic organs, like liver and lung. Phenotypic analyses showed that the majority of CD3+NKp46+ cells coexpressed the CD8αβ heterodimer, while a minor subset expressed the TCR-γδ, which was associated with a CD8αα+ phenotype. Despite these T-cell associated receptors, the majority of CD3+NKp46+ lymphocytes displayed a NK-related phenotype (CD2+CD5−CD6−CD16+perforin+) and expressed mRNA of NKp30, NKp44, and NKG2D at similar levels as NK cells. Functional tests showed that CD3+NKp46+ lymphocytes produced IFN-γ and proliferated upon cytokine stimulation to a similar extent as NK cells, but did not respond to the T-cell mitogen, ConA. Likewise, CD3+NKp46+ cells killed K562 cells with an efficiency comparable to NK cells. Cross-linking of NKp46 and CD3 led to degranulation of CD3+NKp46+ cells, indicating functional signaling pathways for both receptors. Additionally, influenza A(H1N1)pdm09-infected pigs had reduced frequencies of CD3+NKp46+ lymphocytes in blood, but increased frequencies in the lung in the early phase of infection. Thus, CD3+NKp46+ cells appear to be involved in the early phase of influenza infections. In summary, we describe a lymphocyte population in swine with a mixed phenotype of NK and T cells, with results so far indicating that this cell population functionally resembles NK cells. PMID:27471504

  13. Porcine CD3(+)NKp46(+) Lymphocytes Have NK-Cell Characteristics and Are Present in Increased Frequencies in the Lungs of Influenza-Infected Animals.

    PubMed

    Mair, Kerstin H; Stadler, Maria; Talker, Stephanie C; Forberg, Hilde; Storset, Anne K; Müllebner, Andrea; Duvigneau, J Catharina; Hammer, Sabine E; Saalmüller, Armin; Gerner, Wilhelm

    2016-01-01

    The CD3(-)NKp46(+) phenotype is frequently used for the identification of natural killer (NK) cells in various mammalian species. Recently, NKp46 expression was analyzed in more detail in swine. It could be shown that besides CD3(-)NKp46(+) lymphocytes, a small but distinct population of CD3(+)NKp46(+) cells exists. In this study, we report low frequencies of CD3(+)NKp46(+) lymphocytes in blood, lymph nodes, and spleen, but increased frequencies in non-lymphatic organs, like liver and lung. Phenotypic analyses showed that the majority of CD3(+)NKp46(+) cells coexpressed the CD8αβ heterodimer, while a minor subset expressed the TCR-γδ, which was associated with a CD8αα(+) phenotype. Despite these T-cell associated receptors, the majority of CD3(+)NKp46(+) lymphocytes displayed a NK-related phenotype (CD2(+)CD5(-)CD6(-)CD16(+)perforin(+)) and expressed mRNA of NKp30, NKp44, and NKG2D at similar levels as NK cells. Functional tests showed that CD3(+)NKp46(+) lymphocytes produced IFN-γ and proliferated upon cytokine stimulation to a similar extent as NK cells, but did not respond to the T-cell mitogen, ConA. Likewise, CD3(+)NKp46(+) cells killed K562 cells with an efficiency comparable to NK cells. Cross-linking of NKp46 and CD3 led to degranulation of CD3(+)NKp46(+) cells, indicating functional signaling pathways for both receptors. Additionally, influenza A(H1N1)pdm09-infected pigs had reduced frequencies of CD3(+)NKp46(+) lymphocytes in blood, but increased frequencies in the lung in the early phase of infection. Thus, CD3(+)NKp46(+) cells appear to be involved in the early phase of influenza infections. In summary, we describe a lymphocyte population in swine with a mixed phenotype of NK and T cells, with results so far indicating that this cell population functionally resembles NK cells. PMID:27471504

  14. Neutrophil and Alveolar Macrophage-Mediated Innate Immune Control of Legionella pneumophila Lung Infection via TNF and ROS.

    PubMed

    Ziltener, Pascal; Reinheckel, Thomas; Oxenius, Annette

    2016-04-01

    Legionella pneumophila is a facultative intracellular bacterium that lives in aquatic environments where it parasitizes amoeba. However, upon inhalation of contaminated aerosols it can infect and replicate in human alveolar macrophages, which can result in Legionnaires' disease, a severe form of pneumonia. Upon experimental airway infection of mice, L. pneumophila is rapidly controlled by innate immune mechanisms. Here we identified, on a cell-type specific level, the key innate effector functions responsible for rapid control of infection. In addition to the well-characterized NLRC4-NAIP5 flagellin recognition pathway, tumor necrosis factor (TNF) and reactive oxygen species (ROS) are also essential for effective innate immune control of L. pneumophila. While ROS are essential for the bactericidal activity of neutrophils, alveolar macrophages (AM) rely on neutrophil and monocyte-derived TNF signaling via TNFR1 to restrict bacterial replication. This TNF-mediated antibacterial mechanism depends on the acidification of lysosomes and their fusion with L. pneumophila containing vacuoles (LCVs), as well as caspases with a minor contribution from cysteine-type cathepsins or calpains, and is independent of NLRC4, caspase-1, caspase-11 and NOX2. This study highlights the differential utilization of innate effector pathways to curtail intracellular bacterial replication in specific host cells upon L. pneumophila airway infection. PMID:27105352

  15. Neutrophil and Alveolar Macrophage-Mediated Innate Immune Control of Legionella pneumophila Lung Infection via TNF and ROS

    PubMed Central

    Ziltener, Pascal; Reinheckel, Thomas; Oxenius, Annette

    2016-01-01

    Legionella pneumophila is a facultative intracellular bacterium that lives in aquatic environments where it parasitizes amoeba. However, upon inhalation of contaminated aerosols it can infect and replicate in human alveolar macrophages, which can result in Legionnaires’ disease, a severe form of pneumonia. Upon experimental airway infection of mice, L. pneumophila is rapidly controlled by innate immune mechanisms. Here we identified, on a cell-type specific level, the key innate effector functions responsible for rapid control of infection. In addition to the well-characterized NLRC4-NAIP5 flagellin recognition pathway, tumor necrosis factor (TNF) and reactive oxygen species (ROS) are also essential for effective innate immune control of L. pneumophila. While ROS are essential for the bactericidal activity of neutrophils, alveolar macrophages (AM) rely on neutrophil and monocyte-derived TNF signaling via TNFR1 to restrict bacterial replication. This TNF-mediated antibacterial mechanism depends on the acidification of lysosomes and their fusion with L. pneumophila containing vacuoles (LCVs), as well as caspases with a minor contribution from cysteine-type cathepsins or calpains, and is independent of NLRC4, caspase-1, caspase-11 and NOX2. This study highlights the differential utilization of innate effector pathways to curtail intracellular bacterial replication in specific host cells upon L. pneumophila airway infection. PMID:27105352

  16. Naso-pharyngeal mites Halarachne halichoeri (Allman, 1847) in Grey seals stranded on the NW Spanish Atlantic Coast.

    PubMed

    Alonso-Farré, J M; D'Silva, J I Díaz; Gestal, C

    2012-02-10

    In North Atlantic European waters, the nasal mite Halarachne halichoeri has been described affecting Grey seals (Halichoerus grypus) producing different levels of respiratory disease. This study provides data on the prevalence, clinical signs and produced macro-pathology of this parasite mite infecting juvenile wild Grey seals stranded in North-Western Spanish coast. Among the 25 seals examined during the study, a total of 19 had nasal mites in their respiratory upper ways, including adult and larval stages. This represented a percentage of prevalence of 76 ± 8.37. All the live positive seals presented a typical clinical symptomatology associated to upper respiratory tract infections. In dead positive seals, a light to intense sinusitis could be diagnosed macroscopically. The presence of the parasite in the nasal sinuses appears as the primary cause of the high respiratory tract symptomatology presented in most of the juvenile seals stranded in the north coast of Spain. Ultrastructural characterization by scanning electronic microscopy (SEM) has confirmed the taxonomic status of the mite. This identification of H. halichoeri represents the first description of the occurrence of this parasite in Southern Europe.

  17. Identification of developmentally-specific kinotypes and mechanisms of Varroa mite resistance through whole-organism, kinome analysis of honeybee

    PubMed Central

    Robertson, Albert J.; Trost, Brett; Scruten, Erin; Robertson, Thomas; Mostajeran, Mohammad; Connor, Wayne; Kusalik, Anthony; Griebel, Philip; Napper, Scott

    2014-01-01

    Recent investigations associate Varroa destructor (Mesostigmata: Varroidae) parasitism and its associated pathogens and agricultural pesticides with negative effects on colony health, resulting in sporadic global declines in domestic honeybee (Apis mellifera) populations. These events have motivated efforts to develop research tools that can offer insight into the causes of declining bee health as well as identify biomarkers to guide breeding programs. Here we report the development of a bee-specific peptide array for characterizing global cellular kinase activity in whole bee extracts. The arrays reveal distinct, developmentally-specific signaling profiles between bees with differential susceptibility to infestation by Varroa mites. Gene ontology analysis of the differentially phosphorylated peptides indicates that the differential susceptibility to Varroa mite infestation does not reflect compromised immunity; rather, there is evidence for mite-mediated immune suppression within the susceptible phenotype that may reduce the ability of these bees to counter secondary viral infections. This hypothesis is supported by the demonstration of more diverse viral infections in mite-infested, susceptible adult bees. The bee-specific peptide arrays are an effective tool for understanding the molecular basis of this complex phenotype as well as for the discovery and utilization of phosphorylation biomarkers for breeding programs. PMID:24904639

  18. Acaroid mites (Acari: Astigmata) in Chinese traditional medicines.

    PubMed

    Cui, Y-B; Li, C-P; Wang, J; Yang, Q-G; Tian, Y

    2003-12-01

    Almost 2000 samples of the dried plants and animals used in Chinese traditional medicine were collected from a storehouse in Huainan city, Anhui province, China, where they had been kept for at least 6 months. When examined, every sample was found to contain acaroid mites. The mites included representatives of 44 species belonging to 22 genera and seven families. It seems that samples of Chinese traditional medicine frequently become severely infested with mites while in storage. More importance should be attached to protecting the medicines against mite infestation and to protecting against acariasis those who ingest or simply handle the medicines.

  19. Mites associated with stored grain commodities in Benin, West Africa.

    PubMed

    Zannou, Ignace D; Adebo, Habib O; Zannou, Elisabeth; Hell, Kerstin

    2013-12-01

    After insects, mites are the major arthropod pests that inhabit stored agricultural products worldwide. To determine the acarofauna that infests cowpea, maize, paddy rice and sorghum in Benin (West Africa), surveys were conducted in some principal markets (Dantokpa, Glazoue and Parakou) of this country. A total of 555 samples of grains and debris were collected in May and September 2011. More than 56 species belonging to 24 mite families were recorded in the four products. These mite species included predators, parasites, fungivorous, phytophagous and other groups whose feeding habits are not well known. The family Cheyletidae was the most prevalent and the most diverse predatory mite family encountered, in which Cheyletus malaccensis Oudemans was the most abundant species. Several families of mite pests and mites responsible for allergies (Acaridae, Glycyphagidae, Pyroglyphidae, Pyemotidae and Saproglyphidae) were also detected. The three most dominant and frequent species were C. malaccensis, Suidasia nesbitti (Hughes) and Suidasia sp. Statistical analysis showed that densities of these three mite species were higher in Parakou than in Glazoue and Dantokpa, on one hand, and higher in debris than in grains, on the other hand. The densities of S. nesbitti and Suidasia sp. decreased significantly during the dry season, whereas C. malaccensis remained stable throughout the two samplings. Of all grains, sorghum was the least infested with mites. This study shows that in Benin mites are present in stored agricultural products to which they cause serious damage, and may cause various allergies to people.

  20. Effects of potential food sources on biological and demographic parameters of the predatory mites Kampimodromus aberrans, Typhlodromus pyri and Amblyseius andersoni.

    PubMed

    Lorenzon, Mauro; Pozzebon, Alberto; Duso, Carlo

    2012-11-01

    Kampimodromus aberrans, Typhlodromus pyri and Amblyseius andersoni are generalist predatory mites important in controlling tetranychid and eriophyoid mites in European vineyards. They can persist by exploiting various non-prey foods when their main prey is absent or scarce. A comparative analysis of the effects of various prey and non-prey foods on the life history of these predators is lacking. In the laboratory, predatory mites were reared on herbivorous mites (Panonychus ulmi, Eotetranychus carpini and Colomerus vitis), a potential alternative prey (Tydeus caudatus) and two non-prey foods, i.e. the pollen of Typha latifolia and the mycelium of Grape downy mildew (GDM) Plasmopara viticola. Developmental times, survival, sex ratio and fecundity as well as life table parameters were estimated. Kampimodromus aberrans developed faster on E. carpini, C. vitis or pollen than on P. ulmi and laid more eggs on pollen than on prey. Low numbers of this predator developed on GDM infected leaves. Tydeus caudatus was not suitable as prey for any of the three predatory mites. Kampimodromus aberrans showed the highest intrinsic rate of population increase when fed on pollen. Developmental times of T. pyri on prey or pollen were similar but fecundity was higher on pollen than on P. ulmi. Typhlodromus pyri had higher intrinsic rates of population increase on C. vitis and pollen than on P. ulmi; E. carpini showed intermediate values whereas GDM resulted in the lowest r ( m ) values. Development of A. andersoni females was faster on pollen and C. vitis than on P. ulmi and GDM. Fecundity was higher on pollen and mites compared to GDM. Life table parameters of A. andersoni did not differ when predators were fed with prey or pollen while GDM led to a lower r ( m ) value. On a specific diet A. andersoni exhibited faster development and higher fecundity than T. pyri and K. aberrans. These findings improve knowledge on factors affecting the potential of predatory mites in controlling

  1. Evaluation of predatory mite (Acari: Phytoseiidae) releases to suppress spruce spider mites, Oligonychus ununguis (Acari: Tetranychidae), on juniper.

    PubMed

    Shrewsbury, Paula M; Hardin, Mark R

    2003-12-01

    A laboratory trial evaluated four phytoseiid species for their potential as biological control agents of spruce spider mite, Oligonychus ununguis (Jacobi) (Acari: Tetranychidae). An augmentative biological control approach, using the predatory mites Neoseiulus fallacis Garman and Galendromus occidentalis Nesbitt (Acari: Phytoseiidae), was evaluated for reducing pest mite densities and injury, and economic costs on Juniperus chinensis 'Sargentii' A. Henry (Cupressaceae) in an outdoor nursery. Sequential releases of predator species, individually and in combination, were tested and compared with two commonly used miticides, a low-toxicity miticide, horticultural oil, and a conventional miticide, hexythiazox. Timing of treatments was based on grower-determined need, and predator release rates were based on guidelines in literature received from producers of beneficial organisms. Predator releases were more expensive and provided less effective suppression of spruce spider mites, resulting in greater spider mite injury to plants, compared with conventional pesticides. However, spider mite damage to plants did not differ in an economically meaningful way between treatments. Unsatisfactory levels of control seem related to under estimations of actual spider mite abundance based on grower perceptions and the beat sampling technique used to estimate predator release rates. These data suggest that when initial populations of spruce spider mite are high, it is unlikely that sequential releases of predator species, individually or in combination, will suppress spider mite populations. In this trial, augmentative biological control control was 2.5-7 times more expensive than chemical controls.

  2. Scent of a mite: origin and chemical characterization of the lemon-like flavor of mite-ripened cheeses.

    PubMed

    Brückner, Adrian; Heethoff, Michael

    2016-07-01

    Cheese infested with cheese mites is usually treated as unpalatable. Nevertheless, some traditional cheese manufactories in Germany and France intentionally use mites for fermentation of special varieties (i.e. Milbenkäse and Mimolette). While their production includes different mite species, both are characterized by a "lemon-like" flavor. However, the chemical nature and origin of this flavor-component is unknown. The cheese mites possess a pair of opisthosomal glands producing blends of hydrocarbons, terpenes and aromatics. Here, we describe the chemical profiles of the astigmatid mite species Tyrolichus casei (Milbenkäse) and Acarus siro (Mimolette). Although the chemical profiles differ in several aspects, both mite species produce neral (a volatile flavor component of lemon oil), which was absent from the headspace of both cheeses without mites. We conclude that the lemon-like flavor of mite cheese is not a consequence of fermentation of the cheese itself but a component from secretions of the cheese mites. PMID:27059866

  3. Simple sequence repeats together with mismatch repair deficiency can bias mutagenic pathways in Pseudomonas aeruginosa during chronic lung infection.

    PubMed

    Moyano, Alejandro J; Feliziani, Sofía; Di Rienzo, Julio A; Smania, Andrea M

    2013-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen that chronically infects the airways of cystic fibrosis (CF) patients and undergoes a process of genetic adaptation based on mutagenesis. We evaluated the role of mononucleotide G:C and A:T simple sequence repeats (SSRs) in this adaptive process. An in silico survey of the genome sequences of 7 P. aeruginosa strains showed that mononucleotide G:C SSRs but not A:T SSRs were greatly under-represented in coding regions, suggesting a strong counterselection process for G:C SSRs with lengths >5 bp but not for A:T SSRs. A meta-analysis of published whole genome sequence data for a P. aeruginosa strain from a CF patient with chronic airway infection showed that G:C SSRs but not A:T SSRs were frequently mutated during the infection process through the insertion or deletion of one or more SSR subunits. The mutation tendency of G:C SSRs was length-dependent and increased exponentially as a function of SSR length. When this strain naturally became a stable Mismatch Repair System (MRS)-deficient mutator, the degree of increase of G:C SSRs mutations (5-fold) was much higher than that of other types of mutation (2.2-fold or less). Sequence analysis of several mutated genes reported for two different collections, both containing mutator and non-mutator strains of P. aeruginosa from CF chronic infections, showed that the proportion of G:C SSR mutations was significantly higher in mutators than in non-mutators, whereas no such difference was observed for A:T SSR mutations. Our findings, taken together, provide genome-scale evidences that under a MRS-deficient background, long G:C SSRs are able to stochastically bias mutagenic pathways by making the genes in which they are harbored more prone to mutation. The combination of MRS deficiency and virulence-related genes that contain long G:C SSRs is therefore a matter of concern in P. aeruginosa CF chronic infection.

  4. Inhibition of Quorum Sensing-Controlled Virulence Factors and Biofilm Formation in Pseudomonas aeruginosa by Culture Extract from Novel Bacterial Species of Paenibacillus Using a Rat Model of Chronic Lung Infection

    PubMed Central

    Alasil, Saad Musbah; Omar, Rahmat; Yusof, Mohd Yasim

    2015-01-01

    Quorum sensing (QS) is a key regulator of virulence factors and biofilm formation in Gram-negative bacteria such as Pseudomonas aeruginosa. Microorganisms that inhabit soil are of strategic importance in the discovery of compounds with anti-QS properties. The objective of the study was to test the culture extract of a taxonomically novel species of Paenibacillus strain 139SI for its inhibitory effects on the QS-controlled virulence factors and biofilm formation of Pseudomonas aeruginosa both in vitro and in vivo. The Paenibacillus sp. culture extract was used to test its anti-QS effects on the LasA protease, LasB elastase, pyoverdin production, and biofilm formation of P. aeruginosa as well as evaluate its therapeutic effects on lung bacteriology, pathology, hematological profile, and serum antibody responses of experimental animals in a rat model of chronic lung infection. Results showed significant decrease in the activities of QS-controlled LasA protease, LasB elastase pyoverdin, and biofilm formation of P. aeruginosa caused by the culture extract. Moreover, the extract significantly prolonged the survival times of rats and facilitated the clearance of biofilm infections from infected lungs. In conclusion, the antiquorum sensing effects of culture extract from a novel species of Paenibacillus provide new insights to combat biofilm-associated infections. PMID:26904749

  5. Inhibition of Quorum Sensing-Controlled Virulence Factors and Biofilm Formation in Pseudomonas aeruginosa by Culture Extract from Novel Bacterial Species of Paenibacillus Using a Rat Model of Chronic Lung Infection.

    PubMed

    Alasil, Saad Musbah; Omar, Rahmat; Ismail, Salmah; Yusof, Mohd Yasim

    2015-01-01

    Quorum sensing (QS) is a key regulator of virulence factors and biofilm formation in Gram-negative bacteria such as Pseudomonas aeruginosa. Microorganisms that inhabit soil are of strategic importance in the discovery of compounds with anti-QS properties. The objective of the study was to test the culture extract of a taxonomically novel species of Paenibacillus strain 139SI for its inhibitory effects on the QS-controlled virulence factors and biofilm formation of Pseudomonas aeruginosa both in vitro and in vivo. The Paenibacillus sp. culture extract was used to test its anti-QS effects on the LasA protease, LasB elastase, pyoverdin production, and biofilm formation of P. aeruginosa as well as evaluate its therapeutic effects on lung bacteriology, pathology, hematological profile, and serum antibody responses of experimental animals in a rat model of chronic lung infection. Results showed significant decrease in the activities of QS-controlled LasA protease, LasB elastase pyoverdin, and biofilm formation of P. aeruginosa caused by the culture extract. Moreover, the extract significantly prolonged the survival times of rats and facilitated the clearance of biofilm infections from infected lungs. In conclusion, the antiquorum sensing effects of culture extract from a novel species of Paenibacillus provide new insights to combat biofilm-associated infections. PMID:26904749

  6. Immunomodulation of Skin Cytokine Secretion by House Dust Mite Extracts

    PubMed Central

    Arlian, Larry G.; Morgan, Marjorie S.

    2011-01-01

    Background Skin contact with house dust mites may contribute to atopic dermatitis and other skin diseases. We sought to determine if molecules from house dust mites could influence the release of proinflammatory cytokines and chemokines from epidermal keratinocytes and dermal fibroblasts grown in a human skin equivalent (HSE) model. Methods HSEs consisting of an epidermis of keratinocytes with stratum corneum over a dermis of fibroblasts in a collagen matrix were challenged with Dermatophagoides farinae, D. pteronyssinus and Euroglyphus maynei mite extracts. Results HSEs secreted interleukin (IL)-1α, IL-1 receptor antagonist, IL-6, IL-8, cutaneous T cell-attracting chemokine, transforming growth factor-α, granulocyte/macrophage and macrophage colony-stimulating factors and vascular endothelial cell growth factor in response to at least 1 mite extract. Extracts of different mite species stimulated HSEs to release different cytokines. Therefore, extracts of different species contained different molecules or different concentrations of similar molecules. The cytokine release profiles of cells in the HSEs were not the same as for monocultured keratinocytes and fibroblasts. Conclusions Molecules from house dust mites are capable of inducing the release of multiple proinflammatory cytokines and chemokines from epidermal keratinocytes and dermal fibroblasts. Avoiding skin contact with house dust mites would reduce the possibility of mite-induced inflammation in the skin. Therefore, measures to reduce contact with mite molecules such as frequent vacuuming of upholstered furniture and carpets and laundering of clothing and bedding to remove mite molecules and allergens could reduce skin contact with mite molecules and diminish exacerbations of skin inflammation in patients with atopic dermatitis and other skin diseases. PMID:21576987

  7. Epidemiology of Lung Cancer.

    PubMed

    Schwartz, Ann G; Cote, Michele L

    2016-01-01

    Lung cancer continues to be one of the most common causes of cancer death despite understanding the major cause of the disease: cigarette smoking. Smoking increases lung cancer risk 5- to 10-fold with a clear dose-response relationship. Exposure to environmental tobacco smoke among nonsmokers increases lung cancer risk about 20%. Risks for marijuana and hookah use, and the new e-cigarettes, are yet to be consistently defined and will be important areas for continued research as use of these products increases. Other known environmental risk factors include exposures to radon, asbestos, diesel, and ionizing radiation. Host factors have also been associated with lung cancer risk, including family history of lung cancer, history of chronic obstructive pulmonary disease and infections. Studies to identify genes associated with lung cancer susceptibility have consistently identified chromosomal regions on 15q25, 6p21 and 5p15 associated with lung cancer risk. Risk prediction models for lung cancer typically include age, sex, cigarette smoking intensity and/or duration, medical history, and occupational exposures, however there is not yet a risk prediction model currently recommended for general use. As lung cancer screening becomes more widespread, a validated model will be needed to better define risk groups to inform screening guidelines. PMID:26667337

  8. Expression of HIF-1α and P-gp in non-small cell lung cancer and the relationship with HPV infection

    PubMed Central

    Lu, Yimin; Yu, Le-Qun; Zhu, Lixia; Zhao, Nian; Zhou, Xing-Ju; Lu, Xudong

    2016-01-01

    The aim of the study was to study the expression of hypoxia-inducible factor-1α (HIF-1α) and P-glycoprotein (P-gp) and analyze its correlation with human papillomavirus (HPV) infection. From January, 2012 to May, 2014, 72 cases of non-small cell lung cancer (NSCLC) pathologic tissue samples were selected from the study group. Fifty-four lung benign lesions were selected to serve as the control group. HIF-1α and P-gp expression levels were detected using immunohistochemistry. PCR was used to detect the expression of HPV genome employing specific primers for HPV 16 and 18 types. The results showed that there was 47.2 and 63.9% positive HIF-1α and P-gp expression in the study group. No P-gp or HIF-1α expression was detected in the control group. The results established a positive correlation between the expression of HIF-1α and P-gp. In the study group, the expression and differentiation degree of HIF-1α was related to lymphatic metastasis. The HIF-1α expression in the well-differentiated samples was lower than that in the moderate or poorly differentiated samples. HIF-1α expression in patients with lymphatic metastasis was higher than in patients without metastasis. The expression rate of P-gp in adenocarcinoma was higher than that in squamous carcinoma. The detection rate of HPV DNA was 45.83 and 3.70% in the study and control groups, respectively. The HPV infection and differentiation degree had relevance to lymphatic metastasis in the study group. The HPV DNA detection rate in the well-differentiated samples was lower than that in the moderate or poorly differentiated samples. The HPV DNA detection rate in patients with lymphatic metastasis was higher than that in patients with no lymphatic metastasis. There was a close link between HIF-1α, P-gp expression and NSCLC occurrence, and the development of multidrug resistance. In conclusion, the detection of HIF-1α and P-gp expression can effectively predict drug resistance during chemotherapy in NSCLC, and

  9. Clonal dissemination, emergence of mutator lineages and antibiotic resistance evolution in Pseudomonas aeruginosa cystic fibrosis chronic lung infection.

    PubMed

    López-Causapé, Carla; Rojo-Molinero, Estrella; Mulet, Xavier; Cabot, Gabriel; Moyà, Bartolomé; Figuerola, Joan; Togores, Bernat; Pérez, José L; Oliver, Antonio

    2013-01-01

    Chronic respiratory infection by Pseudomonas aeruginosa is a major cause of mortality in cystic fibrosis (CF). We investigated the interplay between three key microbiological aspects of these infections: the occurrence of transmissible and persistent strains, the emergence of variants with enhanced mutation rates (mutators) and the evolution of antibiotic resistance. For this purpose, 10 sequential isolates, covering up to an 8-year period, from each of 10 CF patients were studied. As anticipated, resistance significantly accumulated overtime, and occurred more frequently among mutator variants detected in 6 of the patients. Nevertheless, highest resistance was documented for the nonmutator CF epidemic strain LES-1 (ST-146) detected for the first time in Spain. A correlation between resistance profiles and resistance mechanisms evaluated [efflux pump (mexB, mexD, mexF, and mexY) and ampC overexpression and OprD production] was not always obvious and hypersusceptibility to certain antibiotics (such as aztreonam or meropenem) was frequently observed. The analysis of whole genome macrorestriction fragments through Pulsed-Field Gel Electrophoresis (PFGE) revealed that a single genotype (clone FQSE-A) produced persistent infections in 4 of the patients. Multilocus Sequence typing (MLST) identified clone FQSE-A as the CF epidemic clone ST-274, but striking discrepancies between PFGE and MLST profiles were evidenced. While PFGE macrorestriction patterns remained stable, a new sequence type (ST-1089) was detected in two of the patients, differing from ST-274 by only two point mutations in two of the genes, each leading to a nonpreviously described allele. Moreover, detailed genetic analyses revealed that the new ST-1089 is a mutS deficient mutator lineage that evolved from the epidemic strain ST-274, acquired specific resistance mechanisms, and underwent further interpatient spread. Thus, presented results provide the first evidence of interpatient dissemination of mutator

  10. Colony establishment and maintenance of the eriophyid wheat curl mite Aceria tosichella for controlled transmission studies on a new virus-like pathogen.