Science.gov

Sample records for active maternal immune

  1. Maternal immune activation: Implications for neuropsychiatric disorders.

    PubMed

    Estes, Myka L; McAllister, A Kimberley

    2016-08-19

    Epidemiological evidence implicates maternal infection as a risk factor for autism spectrum disorder and schizophrenia. Animal models corroborate this link and demonstrate that maternal immune activation (MIA) alone is sufficient to impart lifelong neuropathology and altered behaviors in offspring. This Review describes common principles revealed by these models, highlighting recent findings that strengthen their relevance for schizophrenia and autism and are starting to reveal the molecular mechanisms underlying the effects of MIA on offspring. The role of MIA as a primer for a much wider range of psychiatric and neurologic disorders is also discussed. Finally, the need for more research in this nascent field and the implications for identifying and developing new treatments for individuals at heightened risk for neuroimmune disorders are considered. PMID:27540164

  2. Maternal immunization

    PubMed Central

    Moniz, Michelle H; Beigi, Richard H

    2014-01-01

    Maternal immunization holds tremendous promise to improve maternal and neonatal health for a number of infectious conditions. The unique susceptibilities of pregnant women to infectious conditions, as well as the ability of maternally-derived antibody to offer vital neonatal protection (via placental transfer), together have produced the recent increased attention on maternal immunization. The Advisory Committee on Immunization Practices (ACIP) currently recommends 2 immunizations for all pregnant women lacking contraindication, inactivated Influenza and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap). Given ongoing research the number of vaccines recommended during pregnancy is likely to increase. Thus, achieving high vaccination coverage of pregnant women for all recommended immunizations is a key public health enterprise. This review will focus on the present state of vaccine acceptance in pregnancy, with attention to currently identified barriers and determinants of vaccine acceptance. Additionally, opportunities for improvement will be considered. PMID:25483490

  3. Maternal Immune Activation Disrupts Dopamine System in the Offspring

    PubMed Central

    Luchicchi, Antonio; Lecca, Salvatore; Melis, Miriam; De Felice, Marta; Cadeddu, Francesca; Frau, Roberto; Muntoni, Anna Lisa; Fadda, Paola; Devoto, Paola

    2016-01-01

    Background: In utero exposure to maternal viral infections is associated with a higher incidence of psychiatric disorders with a supposed neurodevelopmental origin, including schizophrenia. Hence, immune response factors exert a negative impact on brain maturation that predisposes the offspring to the emergence of pathological phenotypes later in life. Although ventral tegmental area dopamine neurons and their target regions play essential roles in the pathophysiology of psychoses, it remains to be fully elucidated how dopamine activity and functionality are disrupted in maternal immune activation models of schizophrenia. Methods: Here, we used an immune-mediated neurodevelopmental disruption model based on prenatal administration of the polyriboinosinic-polyribocytidilic acid in rats, which mimics a viral infection and recapitulates behavioral abnormalities relevant to psychiatric disorders in the offspring. Extracellular dopamine levels were measured by brain microdialysis in both the nucleus accumbens shell and the medial prefrontal cortex, whereas dopamine neurons in ventral tegmental area were studied by in vivo electrophysiology. Results: Polyriboinosinic-polyribocytidilic acid-treated animals, at adulthood, displayed deficits in sensorimotor gating, memory, and social interaction and increased baseline extracellular dopamine levels in the nucleus accumbens, but not in the prefrontal cortex. In polyriboinosinic-polyribocytidilic acid rats, dopamine neurons showed reduced spontaneously firing rate and population activity. Conclusions: These results confirm that maternal immune activation severely impairs dopamine system and that the polyriboinosinic-polyribocytidilic acid model can be considered a proper animal model of a psychiatric condition that fulfills a multidimensional set of validity criteria predictive of a human pathology. PMID:26819283

  4. Maternal immune activation leads to activated inflammatory macrophages in offspring

    PubMed Central

    Onore, Charity E.; Schwartzer, Jared J.; Careaga, Milo; Bennan, Robert F.; Ashwood, Paul

    2015-01-01

    Several epidemiological studies have shown an association between infection or inflammation during pregnancy and increased risk of autism in the child. In addition, animal models have illustrated that maternal inflammation during gestation can cause autism-relevant behaviors in the offspring; so called maternal immune activation (MIA) models. More recently, permanent changes in T cell cytokine responses were reported in children with autism and in offspring of MIA mice; however, the cytokine responses of other immune cell populations have not been thoroughly investigated in these MIA models. Similar to changes in T cell function, we hypothesized that following MIA, offspring will have long-term changes in macrophage function. To test this theory, we utilized the poly (I:C) MIA mouse model in C57BL/6J mice and examined macrophage cytokine production in adult offspring. Pregnant dams were given either a single injection of 20 mg/kg polyinosinic–polycytidylic acid, poly (I:C), or saline delivered intraperitoneally on gestational day 12.5. When offspring of poly (I:C) treated dams reached 10 weeks of age, femurs were collected and bone marrow-derived macrophages were generated. Cytokine production was measured in bone marrow-derived macrophages incubated for 24 h in either growth media alone, LPS, IL-4/LPS, or IFN-γ/LPS. Following stimulation with LPS alone, or the combination of IFN-γ/LPS, macrophages from offspring of poly (I:C) treated dams produced higher levels of IL-12(p40) (p < 0.04) suggesting an increased M1 polarization. In addition, even without the presence of a polarizing cytokine or LPS stimulus, macrophages from offspring of poly (I:C) treated dams exhibited a higher production of CCL3 (p = 0.05). Moreover, CCL3 levels were further increased when stimulated with LPS, or polarized with either IL-4/LPS or IFN-γ/LPS (p < 0.05) suggesting a general increase in production of this chemokine. Collectively, these data suggest that MIA can produce lasting

  5. Maternal immune activation and abnormal brain development across CNS disorders.

    PubMed

    Knuesel, Irene; Chicha, Laurie; Britschgi, Markus; Schobel, Scott A; Bodmer, Michael; Hellings, Jessica A; Toovey, Stephen; Prinssen, Eric P

    2014-11-01

    Epidemiological studies have shown a clear association between maternal infection and schizophrenia or autism in the progeny. Animal models have revealed maternal immune activation (mIA) to be a profound risk factor for neurochemical and behavioural abnormalities in the offspring. Microglial priming has been proposed as a major consequence of mIA, and represents a critical link in a causal chain that leads to the wide spectrum of neuronal dysfunctions and behavioural phenotypes observed in the juvenile, adult or aged offspring. Such diversity of phenotypic outcomes in the mIA model are mirrored by recent clinical evidence suggesting that infectious exposure during pregnancy is also associated with epilepsy and, to a lesser extent, cerebral palsy in children. Preclinical research also suggests that mIA might precipitate the development of Alzheimer and Parkinson diseases. Here, we summarize and critically review the emerging evidence that mIA is a shared environmental risk factor across CNS disorders that varies as a function of interactions between genetic and additional environmental factors. We also review ongoing clinical trials targeting immune pathways affected by mIA that may play a part in disease manifestation. In addition, future directions and outstanding questions are discussed, including potential symptomatic, disease-modifying and preventive treatment strategies.

  6. Maternal stress, nutrition and physical activity: Impact on immune function, CNS development and psychopathology.

    PubMed

    Marques, Andrea Horvath; Bjørke-Monsen, Anne-Lise; Teixeira, Antônio L; Silverman, Marni N

    2015-08-18

    Evidence suggests that maternal and fetal immune dysfunction may impact fetal brain development and could play a role in neurodevelopmental disorders, although the definitive pathophysiological mechanisms are still not completely understood. Stress, malnutrition and physical inactivity are three maternal behavioral lifestyle factors that can influence immune and central nervous system (CNS) functions in both the mother and fetus, and may therefore, increase risk for neurodevelopmental/psychiatric disorders. First, we will briefly review some aspects of maternal-fetal immune system interactions and development of immune tolerance. Second, we will discuss the bidirectional communication between the immune system and CNS and the pathways by which immune dysfunction could contribute to neurodevelopmental disorders. Third, we will discuss the effects of prenatal stress and malnutrition (over and undernutrition) on perinatal programming of the CNS and immune system, and how this might influence neurodevelopment. Finally, we will discuss the beneficial impact of physical fitness during pregnancy on the maternal-fetal unit and infant and how regular physical activity and exercise can be an effective buffer against stress- and inflammatory-related disorders. Although regular physical activity has been shown to promote neuroplasticity and an anti-inflammatory state in the adult, there is a paucity of studies evaluating its impact on CNS and immune function during pregnancy. Implementing stress reduction, proper nutrition and ample physical activity during pregnancy and the childbearing period may be an efficient strategy to counteract the impact of maternal stress and malnutrition/obesity on the developing fetus. Such behavioral interventions could have an impact on early development of the CNS and immune system and contribute to the prevention of neurodevelopmental and psychiatric disorders. Further research is needed to elucidate this relationship and the underlying

  7. Behavioural deficits associated with maternal immune activation in the rat model of schizophrenia.

    PubMed

    Wolff, Amy R; Cheyne, Kirsten R; Bilkey, David K

    2011-11-20

    Schizophrenia is associated with changes in memory and contextual processing. As maternal infection is a risk factor in schizophrenia we tested for these impairments in a maternal immune activation (MIA) animal model. MIA rats displayed impaired object recognition memory, despite intact object discrimination, and a reduced reinstatement of rearing in response to a contextual manipulation. These results link MIA to contextual impairments in schizophrenia, possibly through changes in hippocampal function.

  8. Region Specific Effects of Maternal Immune Activation on Offspring Neuroimmune Function

    PubMed Central

    Zhou, Heping

    2015-01-01

    Growing evidence suggests that maternal immune activation has a significant impact on the immuno-competence of the offspring. The present study aimed to characterize region-specific effects of maternal immune activation on the offspring’s neuroimmune function. The offspring born to dams treated with saline or lipopolysaccharide (LPS) at gestational day 18 was stimulated with saline or LPS at postnatal day 21, and the mRNA expression of various inflammatory genes in different brain regions of the offspring was analyzed. The offspring born to saline-treated dams exhibited a typical neuroimmune response with elevated levels of cytokines and chemokines following LPS stimulation in all four brain regions examined. In contrast, the offspring born to LPS-treated dams exhibited significantly reduced mRNA induction of cytokines and chemokines following LPS stimulation in the prefrontal cortex but not in the brainstem when compared with pups born to saline-treated dams. Furthermore, the mRNA expression of LPS-induced I-κBζ was significantly attenuated in the prefrontal cortex when compared with pups born to saline-treated dams. These results suggest that maternal LPS may have differential effects on the neuroimmune function in different regions of the offspring brain, and highlight the importance of maternal milieu in the development of neuroimmune function in the offspring. PMID:26229739

  9. Activation of the Maternal Immune System Induces Endocrine Changes in the Placenta via IL-6

    PubMed Central

    Hsiao, Elaine Y.; Patterson, Paul H.

    2011-01-01

    Activation of the maternal immune system in rodent models sets in motion a cascade of molecular pathways that ultimately result in autism- and schizophrenia-related behaviors in offspring. The finding that interleukin-6 (IL-6) is a crucial mediator of these effects led us to examine the mechanism by which this cytokine influences fetal development in vivo. Here we focus on the placenta as the site of direct interaction between mother and fetus and as a principal modulator of fetal development. We find that maternal immune activation (MIA) with a viral mimic, synthetic double-stranded RNA (poly(I:C)), increases IL-6 mRNA as well as maternally-derived IL-6 protein in the placenta. Placentas from MIA mothers exhibit increases in CD69+ decidual macrophages, granulocytes and uterine NK cells, indicating elevated early immune activation. Maternally-derived IL-6 mediates activation of the JAK/STAT3 pathway specifically in the spongiotrophoblast layer of the placenta, which results in expression of acute phase genes. Importantly, this parallels an IL-6-dependent disruption of the growth hormone-insulin-like growth factor (GH-IGF) axis that is characterized by decreased GH, IGFI and IGFBP3 levels. In addition, we observe an IL-6-dependent induction in pro-lactin-like protein-K (PLP-K) expression as well as MIA-related alterations in other placental endocrine factors. Together, these IL-6-mediated effects of MIA on the placenta represent an indirect mechanism by which MIA can alter fetal development. PMID:21195166

  10. Maternal immune transfer in mollusc.

    PubMed

    Wang, Lingling; Yue, Feng; Song, Xiaorui; Song, Linsheng

    2015-02-01

    Maternal immunity refers to the immunity transferred from mother to offspring via egg, playing an important role in protecting the offspring at early life stages and contributing a trans-generational effect on offspring's phenotype. Because fertilization is external in most of the molluscs, oocytes and early embryos are directly exposed to pathogens in the seawater, and thus maternal immunity could provide a better protection before full maturation of their immunological systems. Several innate immune factors including pattern recognition receptors (PRRs) like lectins, and immune effectors like lysozyme, lipopolysaccharide binding protein/bacterial permeability-increasing proteins (LBP/BPI) and antioxidant enzymes have been identified as maternally derived immune factors in mollusc eggs. Among these immune factors, some maternally derived lectins and antibacterial factors have been proved to endue mollusc eggs with effective defense ability against pathogen infection, while the roles of other factors still remain untested. The physiological condition of mollusc broodstock has a profound effect on their offspring fitness. Many other factors such as nutrients, pathogens, environment conditions and pollutants could exert considerable influence on the maternal transfer of immunity. The parent molluscs which have encountered an immune stimulation endow their offspring with a trans-generational immune capability to protect them against infections effectively. The knowledge on maternal transfer of immunity and the trans-generational immune effect could provide us with an ideal management strategy of mollusc broodstock to improve the immunity of offspring and to establish a disease-resistant family for a long-term improvement of cultured stocks.

  11. Maternal Immune Activation Leads to Selective Functional Deficits in Offspring Parvalbumin Interneurons

    PubMed Central

    Canetta, Sarah; Bolkan, Scott; Padilla-Coreano, Nancy; Song, LouJin; Sahn, Ryan; Harrison, Neil; Gordon, Joshua A.; Brown, Alan; Kellendonk, Christoph

    2015-01-01

    Summary Abnormalities in prefrontal GABAergic transmission, particularly in fast-spiking interneurons that express parvalbumin (PV), are hypothesized to contribute to the pathophysiology of multiple psychiatric disorders including schizophrenia, bipolar disorder, anxiety disorders and depression. While primarily histological abnormalities have been observed in patients and in animal models of psychiatric disease, evidence for abnormalities in functional neurotransmission at the level of specific interneuron populations has been lacking in animal models and is difficult to establish in human patients. Using an animal model of a psychiatric disease risk factor, prenatal maternal immune activation (MIA), we found reduced functional GABAergic transmission in the medial prefrontal cortex (mPFC) of adult MIA offspring. Decreased transmission was selective for interneurons expressing PV, and was not observed in calretinin-expressing neurons. This deficit in PV function in MIA offspring was associated with increased anxiety-like behavior and impairments in attentional set shifting, but did not affect working memory. Furthermore, cell-type specific optogenetic inhibition of mPFC PV interneurons was sufficient to impair attentional set shifting and enhance anxiety levels. Finally, we found that in vivo mPFC gamma oscillations, which are supported by PV interneuron function, were linearly correlated with the degree of anxiety displayed in adult mice, and that this correlation was disrupted in MIA offspring. These results demonstrate a selective functional vulnerability of PV interneurons to maternal immune activation, leading to affective and cognitive symptoms that have high relevance for schizophrenia and other psychiatric disorders. PMID:26830140

  12. Impaired synaptic development in a maternal immune activation mouse model of neurodevelopmental disorders

    PubMed Central

    Coiro, Pierluca; Padmashri, Ragunathan; Suresh, Anand; Spartz, Elizabeth; Pendyala, Gurudutt; Chou, Shinnyi; Jung, Yoosun; Meays, Brittney; Roy, Shreya; Gautam, Nagsen; Alnouti, Yazen; Li, Ming; Dunaevsky, Anna

    2016-01-01

    Both genetic and environmental factors are thought to contribute to neurodevelopmental and neuropsychiatric disorders with maternal immune activation (MIA) being a risk factor for both autism spectrum disorders and schizophrenia. Although MIA mouse offspring exhibit behavioral impairments, the synaptic alterations in vivo that mediate these behaviors are not known. Here we employed in vivo multiphoton imaging to determine that in the cortex of young MIA offspring there is a reduction in number and turnover rates of dendritic spines, sites of majority of excitatory synaptic inputs. Significantly, spine impairments persisted into adulthood and correlated with increased repetitive behavior, an ASD relevant behavioral phenotype. Structural analysis of synaptic inputs revealed a reorganization of presynaptic inputs with a larger proportion of spines being contacted by both excitatory and inhibitory presynaptic terminals. These structural impairments were accompanied by altered excitatory and inhibitory synaptic transmission. Finally, we report that a postnatal treatment of MIA offspring with the anti-inflammatory drug ibudilast, prevented both synaptic and behavioral impairments. Our results suggest that a possible altered inflammatory state associated with maternal immune activation results in impaired synaptic development that persists into adulthood but which can be prevented with early anti-inflammatory treatment. PMID:26218293

  13. The suppression of maternal-fetal leukemia inhibitory factor signal relay pathway by maternal immune activation impairs brain development in mice.

    PubMed

    Tsukada, Tsuyoshi; Simamura, Eriko; Shimada, Hiroki; Arai, Takuma; Higashi, Nobuaki; Akai, Takuya; Iizuka, Hideaki; Hatta, Toshihisa

    2015-01-01

    Recent studies in rodents suggest that maternal immune activation (MIA) by viral infection is associated with schizophrenia and autism in offspring. Although maternal IL-6 is though t to be a possible mediator relating MIA induced these neuropsychiatric disorders, the mechanism remains to be elucidated. Previously, we reported that the maternal leukemia inhibitory factor (LIF)-placental ACTH-fetal LIF signaling relay pathway (maternal-fetal LIF signal relay) promotes neurogenesis of fetal cerebrum in rats. Here we report that the maternal-fetal LIF signal relay in mice is suppressed by injection of polyriboinosinic-polyribocytidylic acid into dams, which induces MIA at 12.5 days post-coitum. Maternal IL-6 levels and gene expression of placental suppressor of cytokine signaling 3 (Socs3) increased according to the severity of MIA and gene expression of placental Socs3 correlated with maternal IL-6 levels. Furthermore, we show that MIA causes reduction of LIF level in the fetal cerebrospinal fluid, resulting in the decreased neurogenesis in the cerebrum. These findings suggest that maternal IL-6 interferes the maternal-fetal LIF signal relay by inducing SOCS3 in the placenta and leads to decreased neurogenesis. PMID:26043040

  14. Maternal immune activation evoked by polyinosinic:polycytidylic acid does not evoke microglial cell activation in the embryo

    PubMed Central

    Smolders, Silke; Smolders, Sophie M. T.; Swinnen, Nina; Gärtner, Annette; Rigo, Jean-Michel; Legendre, Pascal; Brône, Bert

    2015-01-01

    Several studies have indicated that inflammation during pregnancy increases the risk for the development of neuropsychiatric disorders in the offspring. Morphological brain abnormalities combined with deviations in the inflammatory status of the brain can be observed in patients of both autism and schizophrenia. It was shown that acute infection can induce changes in maternal cytokine levels which in turn are suggested to affect fetal brain development and increase the risk on the development of neuropsychiatric disorders in the offspring. Animal models of maternal immune activation reproduce the etiology of neurodevelopmental disorders such as schizophrenia and autism. In this study the poly (I:C) model was used to mimic viral immune activation in pregnant mice in order to assess the activation status of fetal microglia in these developmental disorders. Because microglia are the resident immune cells of the brain they were expected to be activated due to the inflammatory stimulus. Microglial cell density and activation level in the fetal cortex and hippocampus were determined. Despite the presence of a systemic inflammation in the pregnant mice, there was no significant difference in fetal microglial cell density or immunohistochemically determined activation level between the control and inflammation group. These data indicate that activation of the fetal microglial cells is not likely to be responsible for the inflammation induced deficits in the offspring in this model. PMID:26300736

  15. Early infections by myxoma virus of young rabbits (Oryctolagus cuniculus) protected by maternal antibodies activate their immune system and enhance herd immunity in wild populations

    PubMed Central

    2014-01-01

    The role of maternal antibodies is to protect newborns against acute early infection by pathogens. This can be achieved either by preventing any infection or by allowing attenuated infections associated with activation of the immune system, the two strategies being based on different cost/benefit ratios. We carried out an epidemiological survey of myxomatosis, which is a highly lethal infectious disease, in two distant wild populations of rabbits to describe the epidemiological pattern of the disease. Detection of specific IgM and IgG enabled us to describe the pattern of immunity. We show that maternal immunity attenuates early infection of juveniles and enables activation of their immune system. This mechanism associated with steady circulation of the myxoma virus in both populations, which induces frequent reinfections of immune rabbits, leads to the maintenance of high immunity levels within populations. Thus, myxomatosis has a low impact, with most infections being asymptomatic. This work shows that infection of young rabbits protected by maternal antibodies induces attenuated disease and activates their immune system. This may play a major role in reducing the impact of a highly lethal disease when ecological conditions enable permanent circulation of the pathogen. PMID:24589193

  16. Early infections by myxoma virus of young rabbits (Oryctolagus cuniculus) protected by maternal antibodies activate their immune system and enhance herd immunity in wild populations.

    PubMed

    Marchandeau, Stéphane; Pontier, Dominique; Guitton, Jean-Sébastien; Letty, Jérôme; Fouchet, David; Aubineau, Jacky; Berger, Francis; Léonard, Yves; Roobrouck, Alain; Gelfi, Jacqueline; Peralta, Brigitte; Bertagnoli, Stéphane

    2014-03-04

    The role of maternal antibodies is to protect newborns against acute early infection by pathogens. This can be achieved either by preventing any infection or by allowing attenuated infections associated with activation of the immune system, the two strategies being based on different cost/benefit ratios. We carried out an epidemiological survey of myxomatosis, which is a highly lethal infectious disease, in two distant wild populations of rabbits to describe the epidemiological pattern of the disease. Detection of specific IgM and IgG enabled us to describe the pattern of immunity. We show that maternal immunity attenuates early infection of juveniles and enables activation of their immune system. This mechanism associated with steady circulation of the myxoma virus in both populations, which induces frequent reinfections of immune rabbits, leads to the maintenance of high immunity levels within populations. Thus, myxomatosis has a low impact, with most infections being asymptomatic. This work shows that infection of young rabbits protected by maternal antibodies induces attenuated disease and activates their immune system. This may play a major role in reducing the impact of a highly lethal disease when ecological conditions enable permanent circulation of the pathogen.

  17. Increased affective ultrasonic communication during fear learning in adult male rats exposed to maternal immune activation.

    PubMed

    Yee, Nicole; Schwarting, Rainer K W; Fuchs, Eberhard; Wöhr, Markus

    2012-09-01

    Maternal exposure to infection during pregnancy greatly increases the risk of psychopathology in the offspring. In support of clinical findings, rodent models of maternal immune activation (MIA) show that prenatal exposure to pathogens can induce phenotypic changes in the offspring associated with schizophrenia, autism, depression and anxiety. In the current study, we investigated the effects of MIA via polyinosinic:polycytidylic acid (poly I:C) on emotional behavior and communication in rats. Pregnant rats were administered poly I:C or saline on gestation day 15 and male offspring were tested in an auditory fear conditioning paradigm in early adulthood. We found that prenatal poly I:C exposure significantly altered affective signaling, namely, the production of aversive 22-kHz ultrasonic vocalizations (USVs), in terms of call number, structure and temporal patterning. MIA led to an increase in aversive 22-kHz USVs to 300% of saline controls. Offspring exposed to MIA not only emitted more 22-kHz USVs, but also emitted calls that were shorter in duration and occurred in bouts containing more calls. The production of appetitive 50-kHz USVs and audible calls was not affected. Intriguingly, alterations in aversive 22-kHz USV emission were observed despite no obvious changes in overt defensive behavior, which highlights the importance of assessing USVs as an additional measure of fear. Aversive 22-kHz USVs are a prominent part of the rat's defensive behavioral repertoire and serve important communicative functions, most notably as alarm calls. The observed changes in aversive 22-kHz USVs show that MIA has long-term effects on emotional behavior and communication in exposed rat offspring.

  18. Increased white matter neuron density in a rat model of maternal immune activation - Implications for schizophrenia.

    PubMed

    Duchatel, Ryan J; Jobling, Phillip; Graham, Brett A; Harms, Lauren R; Michie, Patricia T; Hodgson, Deborah M; Tooney, Paul A

    2016-02-01

    Interstitial neurons are located among white matter tracts of the human and rodent brain. Post-mortem studies have identified increased interstitial white matter neuron (IWMN) density in the fibre tracts below the cortex in people with schizophrenia. The current study assesses IWMN pathology in a model of maternal immune activation (MIA); a risk factor for schizophrenia. Experimental MIA was produced by an injection of polyinosinic:polycytidylic acid (PolyI:C) into pregnant rats on gestational day (GD) 10 or GD19. A separate control group received saline injections. The density of neuronal nuclear antigen (NeuN(+)) and somatostatin (SST(+)) IWMNs was determined in the white matter of the corpus callosum in two rostrocaudally adjacent areas in the 12week old offspring of GD10 (n=10) or GD19 polyI:C dams (n=18) compared to controls (n=20). NeuN(+) IWMN density trended to be higher in offspring from dams exposed to polyI:C at GD19, but not GD10. A subpopulation of these NeuN(+) IWMNs was shown to express SST. PolyI:C treatment of dams induced a significant increase in the density of SST(+) IWMNs in the offspring when delivered at both gestational stages with more regionally widespread effects observed at GD19. A positive correlation was observed between NeuN(+) and SST(+) IWMN density in animals exposed to polyI:C at GD19, but not controls. This is the first study to show that MIA increases IWMN density in adult offspring in a similar manner to that seen in the brain in schizophrenia. This suggests the MIA model will be useful in future studies aimed at probing the relationship between IWMNs and schizophrenia.

  19. Increased white matter neuron density in a rat model of maternal immune activation - Implications for schizophrenia.

    PubMed

    Duchatel, Ryan J; Jobling, Phillip; Graham, Brett A; Harms, Lauren R; Michie, Patricia T; Hodgson, Deborah M; Tooney, Paul A

    2016-02-01

    Interstitial neurons are located among white matter tracts of the human and rodent brain. Post-mortem studies have identified increased interstitial white matter neuron (IWMN) density in the fibre tracts below the cortex in people with schizophrenia. The current study assesses IWMN pathology in a model of maternal immune activation (MIA); a risk factor for schizophrenia. Experimental MIA was produced by an injection of polyinosinic:polycytidylic acid (PolyI:C) into pregnant rats on gestational day (GD) 10 or GD19. A separate control group received saline injections. The density of neuronal nuclear antigen (NeuN(+)) and somatostatin (SST(+)) IWMNs was determined in the white matter of the corpus callosum in two rostrocaudally adjacent areas in the 12week old offspring of GD10 (n=10) or GD19 polyI:C dams (n=18) compared to controls (n=20). NeuN(+) IWMN density trended to be higher in offspring from dams exposed to polyI:C at GD19, but not GD10. A subpopulation of these NeuN(+) IWMNs was shown to express SST. PolyI:C treatment of dams induced a significant increase in the density of SST(+) IWMNs in the offspring when delivered at both gestational stages with more regionally widespread effects observed at GD19. A positive correlation was observed between NeuN(+) and SST(+) IWMN density in animals exposed to polyI:C at GD19, but not controls. This is the first study to show that MIA increases IWMN density in adult offspring in a similar manner to that seen in the brain in schizophrenia. This suggests the MIA model will be useful in future studies aimed at probing the relationship between IWMNs and schizophrenia. PMID:26385575

  20. Maternal immune activation produces neonatal excitability defects in offspring hippocampal neurons from pregnant rats treated with poly I:C

    PubMed Central

    Patrich, Eti; Piontkewitz, Yael; Peretz, Asher; Weiner, Ina; Attali, Bernard

    2016-01-01

    Maternal immune activation (MIA) resulting from prenatal exposure to infectious pathogens or inflammatory stimuli is increasingly recognized to play an important etiological role in neuropsychiatric disorders with neurodevelopmental features. MIA in pregnant rodents induced by injection of the synthetic double-stranded RNA, Poly I:C, a mimic of viral infection, leads to a wide spectrum of behavioral abnormalities as well as structural and functional defects in the brain. Previous MIA studies using poly I:C prenatal treatment suggested that neurophysiological alterations occur in the hippocampus. However, these investigations used only juvenile or adult animals. We postulated that MIA-induced alterations could occur earlier at neonatal/early postnatal stages. Here we examined the neurophysiological properties of cultured pyramidal-like hippocampal neurons prepared from neonatal (P0-P2) offspring of pregnant rats injected with poly I:C. Offspring neurons from poly I:C-treated mothers exhibited significantly lower intrinsic excitability and stronger spike frequency adaptation, compared to saline. A similar lower intrinsic excitability was observed in CA1 pyramidal neurons from hippocampal slices of two weeks-old poly I:C offspring. Cultured hippocampal neurons also displayed lower frequency of spontaneous firing, higher charge transfer of IPSCs and larger amplitude of miniature IPSCs. Thus, maternal immune activation leads to strikingly early neurophysiological abnormalities in hippocampal neurons. PMID:26742695

  1. Maternal antibodies and infant immune responses to vaccines.

    PubMed

    Edwards, Kathryn M

    2015-11-25

    Infants are born with immature immune systems, making it difficult for them to effectively respond to the infectious pathogens encountered shortly after birth. Maternal antibody is actively transported across the placenta and serves to provide protection to the newborn during the first weeks to months of life. However, maternal antibody has been shown repeatedly to inhibit the immune responses of young children to vaccines. The mechanisms for this inhibition are presented and the impact on ultimate immune responses is discussed.

  2. Introduction. Maternal immunization - Promises and concerns.

    PubMed

    Englund, Janet A

    2015-11-25

    In this issue of Vaccine, the maternal immunization platform as an approach to protect mothers and infants against diverse pathogens is presented. Potential vaccine targets and the safety, science, trial designs, ethical considerations, and international perspectives focusing on low and middle income countries (LMIC) are discussed. This information provides a timely update because maternal immunization is increasingly being considered as an intervention to prevent maternal and/or neonatal disease. Prioritization of vaccine targets for maternal immunization by researchers, public health officials and health care workers needs to begin now. PMID:26263199

  3. Maternal immune activation by LPS selectively alters specific gene expression profiles of interneuron migration and oxidative stress in the fetus without triggering a fetal immune response

    PubMed Central

    Oskvig, Devon B.; Elkahloun, Abdel G.; Johnson, Kory R.; Phillips, Terry M.; Herkenham, Miles

    2012-01-01

    Maternal immune activation (MIA) is a risk factor for the development of schizophrenia and autism. Infections during pregnancy activate the mother’s immune system and alter the fetal environment, with consequential effects on CNS function and behavior in the offspring, but the cellular and molecular links between infection-induced altered fetal development and risk for neuropsychiatric disorders are unknown. We investigated the immunological, molecular, and behavioral effects of MIA in the offspring of pregnant Sprague-Dawley rats given an intraperitoneal (0.25 mg/kg) injection of lipopolysaccharide (LPS) on gestational day 15. LPS significantly elevated pro-inflammatory cytokine levels in maternal serum, amniotic fluid, and fetal brain at 4 h, and levels decreased but remained elevated at 24 h. Offspring born to LPS-treated dams exhibited reduced social preference and exploration behaviors as juveniles and young adults. Whole genome microarray analysis of the fetal brain at 4 h post maternal LPS was performed to elucidate the possible molecular mechanisms by which MIA affects the fetal brain. We observed dysregulation of 3,285 genes in restricted functional categories, with increased mRNA expression of cellular stress and cell death genes and reduced expression of developmentally-regulated and brain-specific genes, specifically those that regulate neuronal migration of GABAergic interneurons, including the Distal-less (Dlx) family of transcription factors required for tangential migration from progenitor pools within the ganglionic eminences into the cerebral cortex. Our results provide a novel mechanism by which MIA induces the widespread down-regulation of critical neurodevelopmental genes, including those previously associated with autism. PMID:22310921

  4. Adolescent olanzapine sensitization is correlated with hippocampal stem cell proliferation in a maternal immune activation rat model of schizophrenia.

    PubMed

    Chou, Shinnyi; Jones, Sean; Li, Ming

    2015-08-27

    Previous work established that repeated olanzapine (OLZ) administration in normal adolescent rats induces a sensitization effect (i.e. increased behavioral responsiveness to drug re-exposure) in the conditioned avoidance response (CAR) model. However, it is unclear whether the same phenomenon can be detected in animal models of schizophrenia. The present study explored the generalizability of OLZ sensitization from healthy animals to a preclinical neuroinflammatory model of schizophrenia in the CAR. Maternal immune activation (MIA) was induced via polyinosinic:polycytidylic acid (PolyI:C) administration into pregnant dams. Behavioral assessments of offspring first identified decreased maternal separation-induced pup ultrasonic vocalizations and increased amphetamine-induced hyperlocomotion in animals prenatally exposed to PolyI:C. In addition, repeated adolescent OLZ administration confirmed the generalizability of the sensitization phenomenon. Using the CAR test, adolescent MIA animals displayed a similar increase in behavioral responsiveness after repeated OLZ exposure during both the repeated drug test days as well as a subsequent challenge test. Neurobiologically, few studies examining the relationship between hippocampal cell proliferation and survival and either antipsychotic exposure or MIA have incorporated concurrent behavioral changes. Thus, the current study also sought to reveal the correlation between OLZ behavioral sensitization in the CAR and hippocampal cell proliferation and survival. 5'-bromodeoxyuridine immunohistochemistry identified a positive correlation between the magnitude of OLZ sensitization (i.e. change in avoidance suppression induced by OLZ across days) and hippocampal cell proliferation. The implications of the relationship between behavioral and neurobiological results are discussed.

  5. Changes in Astroglial Markers in a Maternal Immune Activation Model of Schizophrenia in Wistar Rats are Dependent on Sex

    PubMed Central

    de Souza, Daniela F.; Wartchow, Krista M.; Lunardi, Paula S.; Brolese, Giovana; Tortorelli, Lucas S.; Batassini, Cristiane; Biasibetti, Regina; Gonçalves, Carlos-Alberto

    2015-01-01

    Data from epidemiological studies suggest that prenatal exposure to bacterial and viral infection is an important environmental risk factor for schizophrenia. The maternal immune activation (MIA) animal model is used to study how an insult directed at the maternal host can have adverse effects on the fetus, leading to behavioral and neurochemical changes later in life. We evaluated whether the administration of LPS to rat dams during late pregnancy affects astroglial markers (S100B and GFAP) of the offspring in later life. The frontal cortex and hippocampus were compared in male and female offspring on postnatal days (PND) 30 and 60. The S100B protein exhibited an age-dependent pattern of expression, being increased in the frontal cortex and hippocampus of the MIA group at PND 60, while at PND 30, male rats presented increased S100B levels only in the frontal cortex. Considering that S100B secretion is reduced by elevation of glutamate levels, we may hypothesize that this early increment in frontal cortex tissue of males is associated with elevated extracellular levels of glutamate and glutamatergic hypofunction, an alteration commonly associated with SCZ pathology. Moreover, we also found augmented GFAP in the frontal cortex of the LPS group at PND 30, but not in the hippocampus. Taken together data indicate that astroglial changes induced by MIA are dependent on sex and brain region and that these changes could reflect astroglial dysfunction. Such alterations may contribute to our understanding of the abnormal neuronal connectivity and developmental aspects of SCZ and other psychiatric disorders. PMID:26733814

  6. Maternal immunization: opportunities for scientific advancement.

    PubMed

    Beigi, Richard H; Fortner, Kimberly B; Munoz, Flor M; Roberts, Jeff; Gordon, Jennifer L; Han, Htay Htay; Glenn, Greg; Dormitzer, Philip R; Gu, Xing Xing; Read, Jennifer S; Edwards, Kathryn; Patel, Shital M; Swamy, Geeta K

    2014-12-15

    Maternal immunization is an effective strategy to prevent and/or minimize the severity of infectious diseases in pregnant women and their infants. Based on the success of vaccination programs to prevent maternal and neonatal tetanus, maternal immunization has been well received in the United States and globally as a promising strategy for the prevention of other vaccine-preventable diseases that threaten pregnant women and infants, such as influenza and pertussis. Given the promise for reducing the burden of infectious conditions of perinatal significance through the development of vaccines against relevant pathogens, the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) sponsored a series of meetings to foster progress toward clinical development of vaccines for use in pregnancy. A multidisciplinary group of stakeholders convened at the NIH in December 2013 to identify potential barriers and opportunities for scientific advancement in maternal immunization. PMID:25425719

  7. Role of maternally derived immunity in fish.

    PubMed

    Swain, P; Nayak, S K

    2009-08-01

    Maternal immunity is of paramount importance for protection of young ones at early stage of life since the immune factors of an immunocompetent female are transferred transplacentally or through colostrum, milk or yolk to an immunologically naive neonate. Both innate and adaptive type of immunity are transferred of from mother to offspring in fishes. These factors include immunoglobulin (Ig)/antibody, complement factors, lysozymes, protease inhibitors like alpha macroglobulin, different types of lectins and serine proteases like molecules. Among different types of Ig viz. IgM, IgD, IgT/IgZ and IgM-IgZ chimera types, IgM is present in most of the teleostean fishes. In teleosts, IgM either as a reduced/breakdown product or monomeric form is usually transferred to the offsprings. The maternally derived IgM usually persists for a limited duration, exhausts within the completion of yolk absorption process, and completely disappears thereafter during larval stages. Maternal transfer of immunity which provides defense to embryo and larvae depends upon the health as well as the immune status of brood fish. The overall health status of brood fish can affect breeding performances, quality seed production and protection of offsprings. However, factors such as age, maturation, reproductive behaviour and nutrition (micro and macro-nutrients) may affect the immunity in brood fishes. Besides these, seasonal changes such as photoperiods, temperature, adverse environmental conditions, and stress conditions like handling, crowding, and water pollution/contamination can also affect the immunity of brood fishes. The maintenance of the brood stock immunity at high level during vitellogenesis and oogenesis, is utmost important for reducing mortalities at larval/post larval stages through maximum/optimum transfer of maternal immunity. Brood stock immunization prior to breeding as well as selective breeding among the disease resistant families might be the ideal criteria for producing

  8. Cytokine-dependent bidirectional connection between impaired social behavior and susceptibility to seizures associated with maternal immune activation in mice

    PubMed Central

    Washington, James; Kumar, Udaya; Medel-Matus, Jesus-Servando; Shin, Don; Sankar, Raman; Mazarati, Andrey

    2015-01-01

    Maternal immune activation (MIA) results in the development of autism in the offspring via hyperactivation of IL-6 signaling. Furthermore, experimental studies showed that the MIA-associated activation of interleukin-1β (IL-1β) concurrently with IL-6 increases the rate and the severity of hippocampal kindling in mice, thus offering an explanation for autism-epilepsy comorbidity. We examined whether epileptic phenotype triggered by prenatal exposure to IL-6 and IL-1β combination is restricted to kindling or whether it is reproducible in another model of epilepsy, whereby spontaneous seizures develop following kainic acid (KA)- induced status epilepticus. We also examined whether in mice prenatally exposed to IL-6 and IL-6+IL-1β, the presence of spontaneous seizures would exacerbate autism-like features. Between days 12 and 16 of pregnancy, C57bl/6j mice received daily injections of IL-6, IL-1β or IL-6+IL-1β combination. At postnatal day 40, male offspring was examined for the presence of social behavioral deficit and status epilepticus was induced by intrahippocampal KA injection. After six weeks of monitoring for spontaneous seizures, sociability was tested again. Both IL-6 and IL-6+IL-1β offspring presented with social behavioral deficit. Prenatal exposure to IL-6 alleviated, while such exposure to IL-6+IL-1β exacerbated the severity of KA-induced epilepsy. Increased severity of epilepsy in the IL-6+IL-1β mice correlated with the improvement of autism-like behavior. We conclude that complex and not necessarily agonistic relationships exist between epileptic and autism-like phenotypes in an animal model of MIA coupled with KA-induced epilepsy, and that the nature of these relationships depends on components of MIA involved. PMID:26103532

  9. Use of measles supplemental immunization activities (SIAs) as a delivery platform for other maternal and child health interventions: opportunities and challenges.

    PubMed

    Johri, Mira; Sharma, Jitendar K; Jit, Mark; Verguet, Stéphane

    2013-02-18

    Measles supplementary immunization activities (SIAs) offer children in countries with weaker immunization delivery systems like India a second opportunity for measles vaccination. They could also provide a platform to deliver additional interventions, but the feasibility and acceptability of including add-ons is uncertain. We surveyed Indian programme officers involved in the current (2010-2012) measles SIAs concerning opportunities and challenges of using SIAs as a delivery platform for other maternal and child health interventions. Respondents felt that an expanded SIA strategy including add-ons could be of great value in improving access and efficiency. They viewed management challenges, logistics, and safety as the most important potential barriers. They proposed that additional interventions be selected using several criteria, of which importance of the health problem, safety, and contribution to health equity figured most prominently. For children, they recommended inclusion of basic interventions to address nutritional deficiencies, diarrhoea and parasites over vaccines. For mothers, micronutrient interventions were highest ranked.

  10. Implantation: mutual activity of sex steroid hormones and the immune system guarantee the maternal-embryo interaction.

    PubMed

    Gnainsky, Yulia; Dekel, Nava; Granot, Irit

    2014-09-01

    Implantation is strictly dependent on the mutual interaction between a receptive endometrium and the blastocyst. Hence, synchronization between blastocyst development and the acquisition of endometrial receptivity is a prerequisite for the success of this process. This review depicts the cellular and molecular events that coordinate these complex activities. Specifically, the involvement of the sex steroid hormones, estrogen and progesterone, as well as components of the immune system, such as cytokines and specific blood cells, is elaborated. PMID:24959815

  11. Timing of Maternal Immunization Affects Immunological and Behavioral Outcomes of Adult Offspring in Siberian Hamsters (Phodopus sungorus).

    PubMed

    French, Susannah S; Chester, Emily M; Demas, Gregory E

    2016-07-01

    Maternal influences are an important contributing factor to offspring survival, development, and behavior. Common environmental pathogens can induce maternal immune responses and affect subsequent development of offspring. There are likely sensitive periods during pregnancy when animals are particularly vulnerable to environmental disruption. Here we characterize the effects of maternal immunization across pregnancy and postpartum on offspring physiology and behavior in Siberian hamsters (Phodopus sungorus). Hamsters were injected with the antigen keyhole limpet hemocyanin (KLH) (1) prior to pairing with a male (premating), (2) at separation (postmating), (3) at midpregnancy, or (4) after birth (lactation). Maternal food intake, body mass, and immunity were monitored throughout gestation, and litters were measured weekly for growth until adulthood when social behavior, hormone concentrations, and immune responses were determined. We found that immunizations altered maternal immunity throughout pregnancy and lactation. The effects of maternal treatment differed between male and female offspring. Aggressive behavior was enhanced in offspring of both sexes born to mothers treated postmating and thus early in pregnancy relative to other stages. In contrast, maternal treatment and maternal stage differentially affected innate immunity in males and females. Offspring cortisol, however, was unaffected by maternal treatment. Collectively, these data demonstrate that maternal immunization affects offspring physiology and behavior in a time-dependent and sex-specific manner. More broadly, these findings contribute to our understanding of the effects of maternal immune activation, whether it be from environmental exposure or immunization, on immunological and behavioral responses of offspring. PMID:27320639

  12. Transfer of Maternal Antimicrobial Immunity to HIV-Exposed Uninfected Newborns.

    PubMed

    Abu-Raya, Bahaa; Smolen, Kinga K; Willems, Fabienne; Kollmann, Tobias R; Marchant, Arnaud

    2016-01-01

    The transfer of maternal immune factors to the newborn is critical for protection from infectious disease in early life. Maternally acquired passive immunity provides protection until the infant is beyond early life's increased susceptibility to severe infections or until active immunity is achieved following infant's primary immunization. However, as reviewed here, human immunodeficiency virus (HIV) infection alters the transfer of immune factors from HIV-infected mothers to the HIV-exposed newborns and young infants. This may relate to the immune activation in HIV-infected pregnant women, associated with the production of inflammatory cytokines at the maternofetal interface associated with inflammatory responses in the newborn. We also summarize mother-targeting interventions to improve the health of infants born to HIV-infected women, such as immunization during pregnancy and reduction of maternal inflammation. Maternal immunization offers the potential to compensate for the decreased transplacentally transferred maternal antibodies observed in HIV-exposed infants. Current data suggest reduced immunogenicity of vaccines in HIV-infected pregnant women, possibly reducing the protective impact of maternal immunization for HIV-exposed infants. Fortunately, levels of antibodies appear preserved in the breast milk of HIV-infected women, which supports the recommendation to breast-feed during antiretroviral treatment to protect HIV-exposed infants. PMID:27630640

  13. Transfer of Maternal Antimicrobial Immunity to HIV-Exposed Uninfected Newborns

    PubMed Central

    Abu-Raya, Bahaa; Smolen, Kinga K.; Willems, Fabienne; Kollmann, Tobias R.; Marchant, Arnaud

    2016-01-01

    The transfer of maternal immune factors to the newborn is critical for protection from infectious disease in early life. Maternally acquired passive immunity provides protection until the infant is beyond early life’s increased susceptibility to severe infections or until active immunity is achieved following infant’s primary immunization. However, as reviewed here, human immunodeficiency virus (HIV) infection alters the transfer of immune factors from HIV-infected mothers to the HIV-exposed newborns and young infants. This may relate to the immune activation in HIV-infected pregnant women, associated with the production of inflammatory cytokines at the maternofetal interface associated with inflammatory responses in the newborn. We also summarize mother-targeting interventions to improve the health of infants born to HIV-infected women, such as immunization during pregnancy and reduction of maternal inflammation. Maternal immunization offers the potential to compensate for the decreased transplacentally transferred maternal antibodies observed in HIV-exposed infants. Current data suggest reduced immunogenicity of vaccines in HIV-infected pregnant women, possibly reducing the protective impact of maternal immunization for HIV-exposed infants. Fortunately, levels of antibodies appear preserved in the breast milk of HIV-infected women, which supports the recommendation to breast-feed during antiretroviral treatment to protect HIV-exposed infants.

  14. Transfer of Maternal Antimicrobial Immunity to HIV-Exposed Uninfected Newborns

    PubMed Central

    Abu-Raya, Bahaa; Smolen, Kinga K.; Willems, Fabienne; Kollmann, Tobias R.; Marchant, Arnaud

    2016-01-01

    The transfer of maternal immune factors to the newborn is critical for protection from infectious disease in early life. Maternally acquired passive immunity provides protection until the infant is beyond early life’s increased susceptibility to severe infections or until active immunity is achieved following infant’s primary immunization. However, as reviewed here, human immunodeficiency virus (HIV) infection alters the transfer of immune factors from HIV-infected mothers to the HIV-exposed newborns and young infants. This may relate to the immune activation in HIV-infected pregnant women, associated with the production of inflammatory cytokines at the maternofetal interface associated with inflammatory responses in the newborn. We also summarize mother-targeting interventions to improve the health of infants born to HIV-infected women, such as immunization during pregnancy and reduction of maternal inflammation. Maternal immunization offers the potential to compensate for the decreased transplacentally transferred maternal antibodies observed in HIV-exposed infants. Current data suggest reduced immunogenicity of vaccines in HIV-infected pregnant women, possibly reducing the protective impact of maternal immunization for HIV-exposed infants. Fortunately, levels of antibodies appear preserved in the breast milk of HIV-infected women, which supports the recommendation to breast-feed during antiretroviral treatment to protect HIV-exposed infants. PMID:27630640

  15. Maternal immunization. Clinical experiences, challenges, and opportunities in vaccine acceptance.

    PubMed

    Moniz, Michelle H; Beigi, Richard H

    2014-01-01

    Maternal immunization holds tremendous promise to improve maternal and neonatal health for a number of infectious conditions. The unique susceptibilities of pregnant women to infectious conditions, as well as the ability of maternally-derived antibody to offer vital neonatal protection (via placental transfer), together have produced the recent increased attention on maternal immunization. The Advisory Committee on Immunization Practices (ACIP) currently recommends 2 immunizations for all pregnant women lacking contraindication, inactivated Influenza and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap). Given ongoing research the number of vaccines recommended during pregnancy is likely to increase. Thus, achieving high vaccination coverage of pregnant women for all recommended immunizations is a key public health enterprise. This review will focus on the present state of vaccine acceptance in pregnancy, with attention to currently identified barriers and determinants of vaccine acceptance. Additionally, opportunities for improvement will be considered. PMID:25483490

  16. Maternal and developmental immune challenges alter behavior and learning ability of offspring

    PubMed Central

    Grindstaff, Jennifer L.; Hunsaker, Veronica R.; Cox, Shelby N.

    2012-01-01

    Stimulation of the offspring immune response during development is known to influence growth and behavioral phenotype. However, the potential for maternal antibodies to block the behavioral effects of immune activation during the neonatal period has not been assessed. We challenged female zebra finches (Taeniopygia guttata) prior to egg laying and then challenged offspring during the nestling and juvenile periods with one of two antigens (keyhole limpet hemocyanin (KLH) or lipopolysaccharide (LPS)). We then tested the effects of maternal and neonatal immune challenges on offspring growth rates and neophobia and learning ability of offspring during adulthood. Neonatal immune challenge depressed growth rates. Neophobia of adult offspring was influenced by a combination of maternal treatment, offspring treatment, and offspring sex. Males challenged with LPS during the nestling and juvenile periods had reduced learning performance in a novel foraging task; however, female learning was not impacted. Offspring challenged with the same antigen as mothers exhibited similar growth suppression and behavioral changes as offspring challenged with a novel antigen. Thus, developmental immune challenges have long-term effects on the growth and behavioral phenotype of offspring. We found limited evidence that matching of maternal and offspring challenges reduces the effects of immune challenge in the altricial zebra finch. This may be a result of rapid catabolism of maternal antibodies in altricial birds. Our results emphasize the need to address sex differences in the long-term effects of developmental immune challenge and suggest neonatal immune activation may be one proximate mechanism underlying differences in adult behavior. PMID:22522078

  17. Relationship between maternal transfer of immunity and mother fecundity in an insect.

    PubMed

    Zanchi, C; Troussard, J-P; Moreau, J; Moret, Y

    2012-08-22

    Trans-generational immune priming (TGIP) corresponds to the plastic adjustment of offspring immunity as a result of maternal immune experience. TGIP is expected to improve mother's fitness by improving offspring individual performance in an environment where parasitism becomes more prevalent. However, it was recently demonstrated that maternal transfer of immunity to the offspring is costly for immune-challenged female insects. Thus, these females might not provide immune protection to all their offspring because of the inherent cost of other fitness-related traits. Females are therefore expected to adjust their investment to individual offspring immune protection in ways that maximize their fitness. In this study, we investigated how bacterially immune-challenged females of the mealworm beetle, Tenebrio molitor, provision their eggs with immune protection according to egg production. We found that immune-challenged females provide a variable number of their eggs with internal antibacterial activity along egg-laying bouts. Furthermore, within the first immune-protected egg-laying bout (2-4 days after the maternal immune challenge), the number of eggs protected was strongly dependent on the number of eggs produced. Immune-challenged females might therefore adjust their investment into TGIP and fecundity according of their individual perception of the risk of dying from the infection and the expected parasitic conditions for the offspring.

  18. Relationship between maternal transfer of immunity and mother fecundity in an insect.

    PubMed

    Zanchi, C; Troussard, J-P; Moreau, J; Moret, Y

    2012-08-22

    Trans-generational immune priming (TGIP) corresponds to the plastic adjustment of offspring immunity as a result of maternal immune experience. TGIP is expected to improve mother's fitness by improving offspring individual performance in an environment where parasitism becomes more prevalent. However, it was recently demonstrated that maternal transfer of immunity to the offspring is costly for immune-challenged female insects. Thus, these females might not provide immune protection to all their offspring because of the inherent cost of other fitness-related traits. Females are therefore expected to adjust their investment to individual offspring immune protection in ways that maximize their fitness. In this study, we investigated how bacterially immune-challenged females of the mealworm beetle, Tenebrio molitor, provision their eggs with immune protection according to egg production. We found that immune-challenged females provide a variable number of their eggs with internal antibacterial activity along egg-laying bouts. Furthermore, within the first immune-protected egg-laying bout (2-4 days after the maternal immune challenge), the number of eggs protected was strongly dependent on the number of eggs produced. Immune-challenged females might therefore adjust their investment into TGIP and fecundity according of their individual perception of the risk of dying from the infection and the expected parasitic conditions for the offspring. PMID:22535782

  19. Maternal immunization efforts of the National Institutes of Health.

    PubMed

    Rubin, Fran A; Koso-Thomas, Marion; Isaacs, Maggie Brewinski; Piper, Jeanna; Read, Jennifer; Nesin, Mirjana

    2015-11-25

    Over the last 35 years, efforts at the National Institutes of Health (NIH) to protect mothers and their infants against infectious diseases have involved a bench-to-bedside approach. Basic and translational research that provided a foundation for clinical trials of vaccines in pregnancy include natural history and vaccine antigen identification studies. Development of laboratory assays and reagents have been funded by NIAID; these are critical for the advancement of vaccine candidates through the preclinical and clinical steps along the maternal immunization research pathway to support vaccine efficacy. Animal models of maternal immunization have been developed to evaluate efficacy of vaccine candidates. Clinical studies required development of maternal immunization protocols to address specific pregnancy related issues, for enrollment and safety assessment of mothers and their infants. NIH has organized and participated in meetings, workshops and other collaborative efforts with partners have advanced maternal immunization efforts. Partners have included many institutes and offices at NIH as well as other Department of Health and Human Services agencies and offices (Food and Drug Administration, Centers for Disease Control and Prevention, National Vaccine Program Office), World Health Organization, academic investigators, Biotech and pharmaceutical companies, and nonprofit organizations such as the Bill and Melinda Gates Foundation. These research and development partnership are essential for advancing maternal immunization. Continued efforts are needed to promote maternal immunization to protect pregnant women and their infants against vaccine-preventable infectious disease, especially in resource-limited settings where the burden of infections is high. PMID:26458798

  20. Maternal immunization efforts of the National Institutes of Health.

    PubMed

    Rubin, Fran A; Koso-Thomas, Marion; Isaacs, Maggie Brewinski; Piper, Jeanna; Read, Jennifer; Nesin, Mirjana

    2015-11-25

    Over the last 35 years, efforts at the National Institutes of Health (NIH) to protect mothers and their infants against infectious diseases have involved a bench-to-bedside approach. Basic and translational research that provided a foundation for clinical trials of vaccines in pregnancy include natural history and vaccine antigen identification studies. Development of laboratory assays and reagents have been funded by NIAID; these are critical for the advancement of vaccine candidates through the preclinical and clinical steps along the maternal immunization research pathway to support vaccine efficacy. Animal models of maternal immunization have been developed to evaluate efficacy of vaccine candidates. Clinical studies required development of maternal immunization protocols to address specific pregnancy related issues, for enrollment and safety assessment of mothers and their infants. NIH has organized and participated in meetings, workshops and other collaborative efforts with partners have advanced maternal immunization efforts. Partners have included many institutes and offices at NIH as well as other Department of Health and Human Services agencies and offices (Food and Drug Administration, Centers for Disease Control and Prevention, National Vaccine Program Office), World Health Organization, academic investigators, Biotech and pharmaceutical companies, and nonprofit organizations such as the Bill and Melinda Gates Foundation. These research and development partnership are essential for advancing maternal immunization. Continued efforts are needed to promote maternal immunization to protect pregnant women and their infants against vaccine-preventable infectious disease, especially in resource-limited settings where the burden of infections is high.

  1. Strategies To Boost Maternal Immunization To Achieve Further Gains In Improved Maternal And Newborn Health.

    PubMed

    Steedman, Mark R; Kampmann, Beate; Schillings, Egbert; Al Kuwari, Hanan; Darzi, Ara

    2016-02-01

    Despite the indisputable successes of the United Nations Millennium Development Goals, which include goals on improving maternal health and reducing child mortality, millions of mothers and newborns still die tragically and unnecessarily each year. Many of these deaths result from vaccine-preventable diseases, since obstacles such as cost and accessibility have hampered efforts to deliver efficacious vaccines to those most in need. Additionally, many vaccines given to mothers and children under age five are not suitable for newborns, since their maturing immune systems do not respond optimally during the first few months of life. Maternal immunization-the process by which a pregnant woman's immune system is fortified against a particular disease and the protection is then transferred to her unborn child-has emerged as a strategy to prevent many unnecessary maternal and newborn deaths. We review vaccines that are already used for maternal immunization, analyze vaccines under development that could be used for maternal immunization strategies in the future, and recommend that policy makers use maternal immunization for improved maternal and newborn health. PMID:26858385

  2. Strategies To Boost Maternal Immunization To Achieve Further Gains In Improved Maternal And Newborn Health.

    PubMed

    Steedman, Mark R; Kampmann, Beate; Schillings, Egbert; Al Kuwari, Hanan; Darzi, Ara

    2016-02-01

    Despite the indisputable successes of the United Nations Millennium Development Goals, which include goals on improving maternal health and reducing child mortality, millions of mothers and newborns still die tragically and unnecessarily each year. Many of these deaths result from vaccine-preventable diseases, since obstacles such as cost and accessibility have hampered efforts to deliver efficacious vaccines to those most in need. Additionally, many vaccines given to mothers and children under age five are not suitable for newborns, since their maturing immune systems do not respond optimally during the first few months of life. Maternal immunization-the process by which a pregnant woman's immune system is fortified against a particular disease and the protection is then transferred to her unborn child-has emerged as a strategy to prevent many unnecessary maternal and newborn deaths. We review vaccines that are already used for maternal immunization, analyze vaccines under development that could be used for maternal immunization strategies in the future, and recommend that policy makers use maternal immunization for improved maternal and newborn health.

  3. Regulation of costimulatory signal in maternal-fetal immune tolerance.

    PubMed

    Jin, Li-Ping; Fan, Deng-Xuan; Li, Da-Jin

    2011-08-01

    A pregnancy is associated with modifications in the immune status of the mother, but the mechanisms are not well understood. Several observations have indicated that CD28/CTLA-4 and B7-1/B7-2 are involved in the maternal-fetal immune regulation. This review aims to recapitulate our current knowledge concerning the role of CD28/CTLA-4 and B7-1/B7-2 in maternal-fetal immune regulation. Several studies suggest that up-regulation of B7-2 and/or CD28 and/or down-regulation of CTLA-4 are correlated with the occurrence of pregnancy loss. Therefore, an accurate expression of costimulatory molecules at the maternal-fetal interface may ensure that the decidual cells do not elicit a 'danger' signal to the maternal immune system, perhaps instead contributing to the establishment of immune tolerance in vivo. It is showed that costimulation blockade with anti-B7 mAbs results in altered allogeneic T-cell response and overcomes increased maternal rejection to the fetus, which improves fetus growth in the abortion-prone system. These findings suggest that the anti-B7-treated T cells not only function as potent suppresser cells but also exert immunoregulatory effect on the maternal T cells. This procedure might be potentially useful to immunotherapy for human recurrent spontaneous abortion. PMID:21276120

  4. Alteration of imprinted Dlk1-Dio3 miRNA cluster expression in the entorhinal cortex induced by maternal immune activation and adolescent cannabinoid exposure

    PubMed Central

    Hollins, S L; Zavitsanou, K; Walker, F R; Cairns, M J

    2014-01-01

    A significant feature of the cortical neuropathology of schizophrenia is a disturbance in the biogenesis of short non-coding microRNA (miRNA) that regulate translation and stability of mRNA. While the biological origin of this phenomenon has not been defined, it is plausible that it relates to major environmental risk factors associated with the disorder such as exposure to maternal immune activation (MIA) and adolescent cannabis use. To explore this hypothesis, we administered the viral mimic poly I:C to pregnant rats and further exposed some of their maturing offsprings to daily injections of the synthetic cannabinoid HU210 for 14 days starting on postnatal day 35. Whole-genome miRNA expression analysis was then performed on the left and right hemispheres of the entorhinal cortex (EC), a region strongly associated with schizophrenia. Animals exposed to either treatment alone or in combination exhibited significant differences in the expression of miRNA in the left hemisphere, whereas the right hemisphere was less responsive. Hemisphere-associated differences in miRNA expression were greatest in the combined treatment and highly over-represented in a single imprinted locus on chromosome 6q32. This observation was significant as the syntenic 14q32 locus in humans encodes a large proportion of miRNAs differentially expressed in peripheral blood lymphocytes from patients with schizophrenia, suggesting that interaction of early and late environmental insults may affect miRNA expression, in a manner that is relevant to schizophrenia. PMID:25268256

  5. Linkages between maternal education and childhood immunization in India.

    PubMed

    Vikram, Kriti; Vanneman, Reeve; Desai, Sonalde

    2012-07-01

    While correlations between maternal education and child health have been observed in diverse parts of the world, the causal pathways explaining how maternal education improves child health remain far from clear. Using data from the nationally representative India Human Development Survey of 2004-5, this analysis examines four possible pathways that may mediate the influence of maternal education on childhood immunization: greater human, social, and cultural capitals and more autonomy within the household. Data from 5287 households in India show the familiar positive relationship between maternal education and childhood immunization even after extensive controls for socio-demographic characteristics and village- and neighborhood-fixed effects. Two pathways are important: human capital (health knowledge) is an especially important advantage for mothers with primary education, and cultural capital (communication skills) is important for mothers with some secondary education and beyond.

  6. Incorporating immunizations into routine obstetric care to facilitate Health Care Practitioners in implementing maternal immunization recommendations

    PubMed Central

    Webb, Heather; Street, Jackie; Marshall, Helen

    2014-01-01

    Immunization against pertussis, influenza, and rubella reduces morbidity and mortality in pregnant women and their offspring. Health care professionals (HCPs) caring for women perinatally are uniquely placed to reduce maternal vaccine preventable diseases (VPDs). Despite guidelines recommending immunization during the perinatal period, maternal vaccine uptake remains low. This qualitative study explored the role of obstetricians, general practitioners, and midwives in maternal vaccine uptake. Semi-structured interviews (n = 15) were conducted with perinatal HCPs at a tertiary maternity hospital in South Australia. HCPs were asked to reflect on their knowledge, beliefs, and practice relating to immunization advice and vaccine provision. Interviews were transcribed and coded using thematic analysis. Data collection and analysis was an iterative process, with collection ceasing with theoretical saturation. Participants unanimously supported maternal vaccination as an effective way of reducing risk of disease in this vulnerable population, however only rubella immunity detection and immunization is embedded in routine care. Among these professionals, delegation of responsibility for maternal immunization was unclear and knowledge about maternal immunization was variable. Influenza and pertussis vaccine prevention measures were not included in standard pregnancy record documentation, information provision to patients was “ad hoc” and vaccinations not offered on-site. The key finding was that the incorporation of maternal vaccinations into standard care through a structured process is an important facilitator for immunization uptake. Incorporating vaccine preventable disease management measures into routine obstetric care including incorporation into the Pregnancy Record would facilitate HCPs in implementing recommendations. Rubella prevention provides a useful “template” for other vaccines. PMID:24509790

  7. The impact of maternal obesity during pregnancy on offspring immunity.

    PubMed

    Wilson, Randall M; Messaoudi, Ilhem

    2015-12-15

    In the United States, approximately 64% of women of childbearing age are either overweight or obese. Maternal obesity during pregnancy is associated with a greater risk for adverse maternal-fetal outcomes. Adverse health outcomes for the offspring can persist into adulthood, increasing the incidence of several chronic conditions including cardiovascular disease, diabetes, and asthma. Since these diseases have a significant inflammatory component, these observations are indicative of perturbation of the normal development and maturation of the immune system of the offspring in utero. This hypothesis is strongly supported by data from several rodent studies. Although the mechanisms of these perturbations are not fully understood, it is thought that increased placental inflammation due to obesity may directly affect neonatal development through alterations in nutrient transport. In this review we examine the impact of maternal obesity on the neonatal immune system, and potential mechanisms for the changes observed.

  8. The maternal microbiota drives early postnatal innate immune development.

    PubMed

    Gomez de Agüero, Mercedes; Ganal-Vonarburg, Stephanie C; Fuhrer, Tobias; Rupp, Sandra; Uchimura, Yasuhiro; Li, Hai; Steinert, Anna; Heikenwalder, Mathias; Hapfelmeier, Siegfried; Sauer, Uwe; McCoy, Kathy D; Macpherson, Andrew J

    2016-03-18

    Postnatal colonization of the body with microbes is assumed to be the main stimulus to postnatal immune development. By transiently colonizing pregnant female mice, we show that the maternal microbiota shapes the immune system of the offspring. Gestational colonization increases intestinal group 3 innate lymphoid cells and F4/80(+)CD11c(+) mononuclear cells in the pups. Maternal colonization reprograms intestinal transcriptional profiles of the offspring, including increased expression of genes encoding epithelial antibacterial peptides and metabolism of microbial molecules. Some of these effects are dependent on maternal antibodies that potentially retain microbial molecules and transmit them to the offspring during pregnancy and in milk. Pups born to mothers transiently colonized in pregnancy are better able to avoid inflammatory responses to microbial molecules and penetration of intestinal microbes. PMID:26989247

  9. Maternal adaptive immunity influences the intestinal microflora of suckling mice.

    PubMed

    Diaz, Rosa L; Hoang, Lisa; Wang, Jiafang; Vela, Jose L; Jenkins, Shannon; Aranda, Richard; Martín, Martín G

    2004-09-01

    The microflorae in the intestine of breast-fed infants are distinct from those that typically populate the intestine of formula-fed infants. Although the acquisition of passive immunity through breast-feeding may play a critical role in influencing the pattern of bacterial colonization of the gut, the precise mechanisms underlying the differences in the commensal microflorae of breast and formula-fed children have not been established. We hypothesized that the assemblage of commensal microflorae in suckling and weaned mice may be influenced by the maternal adaptive immune system. To test this hypothesis, we analyzed the intestinal microflorae of mice reared in the presence (wild-type) or absence of an intact maternal immune system (T- and B-cell deficient). Several types of bacteria (Lactobacillus, Enterococcus, Clostridium perfringens, Bifidobacterium, and Bacteroides) were isolated and enumerated from both the small and large intestine of 10-, 18-, 25- and 40- to 60-d old mice using selective media. The densities of bacteria were significantly lower in the small intestine of weaned mice that were reared by wild-type (WT) compared with immunodeficient (ID) dams. However, the microflorae were generally more abundant in the large intestine of suckling pups reared by WT compared with ID dams. Our results indicate that intestinal microflorae change throughout the suckling phase of development and that the maternal adaptive immune system influences the pattern and abundance of bacteria within the gut in an age- and site-specific manner.

  10. Maternal Education and Immunization Status Among Children in Kenya.

    PubMed

    Onsomu, Elijah O; Abuya, Benta A; Okech, Irene N; Moore, DaKysha; Collins-McNeil, Janice

    2015-08-01

    Child morbidity and mortality due to infectious diseases continues to be a major threat and public health concern worldwide. Although global vaccination coverage reached 90 % for diphtheria, tetanus and pertussis (DTP3) across 129 countries, Kenya and other sub-Saharan countries continue to experience under-vaccination. The purpose of this study was to examine the association between maternal education and child immunization (12-23 months) in Kenya. This study used retrospective cross-sectional data from the 2008-2009 Kenya Demographic and Health Survey for women aged 15-49, who had children aged 12-23 months, and who answered questions about vaccination in the survey (n = 1,707). The majority of the children had received vaccinations, with 77 % for poliomyelitis, 74 % for measles, 94 % for tuberculosis, and 91 % for diphtheria, whooping cough (pertussis), and tetanus. After adjusting for other covariates, women with primary, secondary, and college/university education were between 2.21 (p < 0.01) and 9.10 (p < 0.001) times more likely to immunize their children than those who had less than a primary education. Maternal education is clearly crucial in ensuring good health outcomes among children, and integrating immunization knowledge with maternal and child health services is imperative. More research is needed to identify factors influencing immunization decisions among less-educated women in Kenya.

  11. Maternal education, child immunizations, and public policy: evidence from the US National Immunization Survey.

    PubMed

    Racine, Andrew D; Joyce, Theodore J

    2007-10-01

    This article measures the independent association of maternal education level and childhood immunization rates in the USA and compares the associations in states that provide free vaccines to all residents (Universal) and those that do not (non-Universal). To do this, the US-based National Immunization Survey data from 1995 to 2003 for children 19-35 months of age were analyzed. Unadjusted estimates of up-to-date status for the 4:3:1:3:3 series and the pneumococcal conjugate vaccine were estimated by the level of maternal education. Linear probability regressions produced adjusted estimates of maternal education effects controlling for covariates. Adjusting for race/ethnicity, income, and other covariates, children of mothers with less than high school education were found to be 7.8% (p<0.05) less likely than children of mothers with college education to be up-to-date for the 4:3:1:3:3 vaccine series. For the newer pneumococcal conjugate vaccine, these children were 4.5% (p<0.05) less likely to be up-to-date. Residence in a Universal state was found to significantly attenuate these effects. As such, higher maternal education, independent of income and race/ethnicity is associated with improved child immunization rates, but subsidizing immunization choices diminishes the disadvantage associated with lower maternal educational achievement. PMID:17643686

  12. Estimating Genetic and Maternal Effects Determining Variation in Immune Function of a Mixed-Mating Snail.

    PubMed

    Seppälä, Otto; Langeloh, Laura

    2016-01-01

    Evolution of host defenses such as immune function requires heritable genetic variation in them. However, also non-genetic maternal effects can contribute to phenotypic variation, thus being an alternative target for natural selection. We investigated the role of individuals' genetic background and maternal effects in determining immune defense traits (phenoloxidase and antibacterial activity of hemolymph), as well as in survival and growth, in the simultaneously hermaphroditic snail Lymnaea stagnalis. We utilized the mixed mating system of this species by producing full-sib families in which each parental snail had produced offspring as both a dam and as a sire, and tested whether genetic background (family) and non-genetic maternal effects (dam nested within family) explain trait variation. Immune defense traits and growth were affected solely by individuals' genetic background. Survival of snails did not show family-level variation. Additionally, some snails were produced through self-fertilization. They showed reduced growth and survival suggesting recessive load or overdominance. Immune defense traits did not respond to inbreeding. Our results suggest that the variation in snail immune function and growth was due to genetic differences. Since immune traits did not respond to inbreeding, this variation is most likely due to additive or epistatic genetic variance. PMID:27551822

  13. Estimating Genetic and Maternal Effects Determining Variation in Immune Function of a Mixed-Mating Snail

    PubMed Central

    Seppälä, Otto; Langeloh, Laura

    2016-01-01

    Evolution of host defenses such as immune function requires heritable genetic variation in them. However, also non-genetic maternal effects can contribute to phenotypic variation, thus being an alternative target for natural selection. We investigated the role of individuals’ genetic background and maternal effects in determining immune defense traits (phenoloxidase and antibacterial activity of hemolymph), as well as in survival and growth, in the simultaneously hermaphroditic snail Lymnaea stagnalis. We utilized the mixed mating system of this species by producing full-sib families in which each parental snail had produced offspring as both a dam and as a sire, and tested whether genetic background (family) and non-genetic maternal effects (dam nested within family) explain trait variation. Immune defense traits and growth were affected solely by individuals’ genetic background. Survival of snails did not show family-level variation. Additionally, some snails were produced through self-fertilization. They showed reduced growth and survival suggesting recessive load or overdominance. Immune defense traits did not respond to inbreeding. Our results suggest that the variation in snail immune function and growth was due to genetic differences. Since immune traits did not respond to inbreeding, this variation is most likely due to additive or epistatic genetic variance. PMID:27551822

  14. Maternal influences on fetal microbial colonization and immune development.

    PubMed

    Romano-Keeler, Joann; Weitkamp, Jörn-Hendrik

    2015-01-01

    While critical for normal development, the exact timing of establishment of the intestinal microbiome is unknown. For example, although preterm labor and birth have been associated with bacterial colonization of the amniotic cavity and fetal membranes for many years, the prevailing dogma of a sterile intrauterine environment during normal term pregnancies has been challenged more recently. While found to be a key contributor of evolution in the animal kingdom, maternal transmission of commensal bacteria may also constitute a critical process during healthy pregnancies in humans with yet unclear developmental importance. Metagenomic sequencing has elucidated a rich placental microbiome in normal term pregnancies likely providing important metabolic and immune contributions to the growing fetus. Conversely, an altered microbial composition during pregnancy may produce aberrant metabolites impairing fetal brain development and life-long neurological outcomes. Here we review the current understanding of microbial colonization at the feto-maternal interface and explain how normal gut colonization drives a balanced neonatal mucosal immune system, while dysbiosis contributes to aberrant immune function early in life and beyond. We discuss how maternal genetics, diet, medications, and probiotics inform the fetal microbiome in preparation for perinatal and postnatal bacterial colonization.

  15. Immune Suppression and Immune Activation in Depression

    PubMed Central

    Blume, Joshua; Douglas, Steven D.; Evans, Dwight L.

    2010-01-01

    Depression has been characterized as a disorder of both immune suppression and immune activation. Markers of impaired cellular immunity (decreased natural killer cell cytotoxicity) and inflammation (elevated IL-6, TNFα, CRP) have been associated with depression. These immunological markers have been associated with other medical illnesses, suggesting that immune dysregulation may be a central feature common to both depression and to its frequent medical comorbidities. Yet the significant associations of findings of both immune suppression and immune activation with depression raise questions concerning the relationship between these two classes of immunological observations. Depressed populations are heterogeneous groups, and there may be differences in the immune profiles of populations that are more narrowly defined in terms of symptom profile and/or demographic features. There have been few reports concurrently investigating markers of immune suppression and immune activation in the same depressed individuals. An emerging preclinical literature suggests that chronic inflammation may directly contribute to the pathophysiology of immune suppression in the context of illnesses such as cancer and rheumatoid arthritis. This literature provides us with specific immunoregulatory mechanisms mediating these relationships that could also explain differences in immune disturbances between subsets of depressed individuals We propose a research agenda emphasizing the assessment of these immunoregulatory mechanisms in large samples of depressed subjects as a means to define the relationships among immune findings (suppression and/or activation) within the same depressed individuals and to characterize subsets of depressed subjects based on shared immune profiles. Such a program of research, building on and integrating our knowledge of the psychoneuroimmunology of depression, could lead to innovation in the assessment and treatment of depression and its medical comorbidities

  16. Prenatal maternal stress exposure and immune function in the offspring.

    PubMed

    Veru, Franz; Laplante, David P; Luheshi, Giamal; King, Suzanne

    2014-03-01

    The intra-uterine environment provides the first regulatory connection for the developing fetus and shapes its physiological responses in preparation for postnatal life. Psychological stress acts as a programming determinant by setting functional parameters to abnormal levels, thus inducing postnatal maladaptation. The effects of prenatal maternal stress (PNMS) on the developing immune system have been documented mostly through animal studies, but inconsistent results and methodological differences have hampered the complete understanding of these findings. As the immune system follows a similar ontogenic pattern in all mammals, a translational framework based on the developmental windows of vulnerability proposed by immunotoxicology studies was created to integrate these findings. The objective of this review is to examine the available literature on PNMS and immune function in the offspring through the above framework and gain a better understanding of these results by elucidating the moderating influence of the stressor type, timing and duration, and the offspring species, sex and age at assessment. The evaluation of the literature through this framework showed that the effects of PNMS are parameter specific: the moderating effects of timing in gestation were relevant for lymphocyte population numbers, Natural Killer cell function and mitogen-induced proliferation. The presence of an important and directional sexual dimorphism was evident and the influence of the type or duration of PNMS paralleled that of stress in non-pregnant animals. In conclusion, PNMS is a relevant factor in the programming of immune function. Its consequences may be related to disorders with an important immune component such as allergies.

  17. Intranasal Immunization of Mice to Avoid Interference of Maternal Antibody against H5N1 Infection.

    PubMed

    Zhang, Fenghua; Peng, Bo; Chang, Haiyan; Zhang, Ran; Lu, Fangguo; Wang, Fuyan; Fang, Fang; Chen, Ze

    2016-01-01

    Maternally-derived antibodies (MDAs) can protect offspring against influenza virus infection but may also inhibit active immune responses. To overcome MDA- mediated inhibition, active immunization of offspring with an inactivated H5N1 whole-virion vaccine under the influence of MDAs was explored in mice. Female mice were vaccinated twice via the intraperitoneal (IP) or intranasal (IN) route with the vaccine prior to mating. One week after birth, the offspring were immunized twice via the IP or IN route with the same vaccine and then challenged with a lethal dose of a highly homologous virus strain. The results showed that, no matter which immunization route (IP or IN) was used for mothers, the presence of MDAs severely interfered with the active immune response of the offspring when the offspring were immunized via the IP route. Only via the IN immunization route did the offspring overcome the MDA interference. These results suggest that intranasal immunization could be a suitable inoculation route for offspring to overcome MDA interference in the defense against highly pathogenic H5N1 virus infection. This study may provide references for human and animal vaccination to overcome MDA-induced inhibition. PMID:27280297

  18. Intranasal Immunization of Mice to Avoid Interference of Maternal Antibody against H5N1 Infection

    PubMed Central

    Zhang, Fenghua; Peng, Bo; Chang, Haiyan; Zhang, Ran; Lu, Fangguo; Wang, Fuyan; Fang, Fang

    2016-01-01

    Maternally-derived antibodies (MDAs) can protect offspring against influenza virus infection but may also inhibit active immune responses. To overcome MDA- mediated inhibition, active immunization of offspring with an inactivated H5N1 whole-virion vaccine under the influence of MDAs was explored in mice. Female mice were vaccinated twice via the intraperitoneal (IP) or intranasal (IN) route with the vaccine prior to mating. One week after birth, the offspring were immunized twice via the IP or IN route with the same vaccine and then challenged with a lethal dose of a highly homologous virus strain. The results showed that, no matter which immunization route (IP or IN) was used for mothers, the presence of MDAs severely interfered with the active immune response of the offspring when the offspring were immunized via the IP route. Only via the IN immunization route did the offspring overcome the MDA interference. These results suggest that intranasal immunization could be a suitable inoculation route for offspring to overcome MDA interference in the defense against highly pathogenic H5N1 virus infection. This study may provide references for human and animal vaccination to overcome MDA-induced inhibition. PMID:27280297

  19. Human cytomegalovirus induces a distinct innate immune response in the maternal-fetal interface.

    PubMed

    Weisblum, Yiska; Panet, Amos; Zakay-Rones, Zichria; Vitenshtein, Alon; Haimov-Kochman, Ronit; Goldman-Wohl, Debra; Oiknine-Djian, Esther; Yamin, Rachel; Meir, Karen; Amsalem, Hagai; Imbar, Tal; Mandelboim, Ofer; Yagel, Simcha; Wolf, Dana G

    2015-11-01

    The initial interplay between human cytomegalovirus (HCMV) and innate tissue response in the human maternal-fetal interface, though crucial for determining the outcome of congenital HCMV infection, has remained unknown. We studied the innate response to HCMV within the milieu of the human decidua, the maternal aspect of the maternal-fetal interface, maintained ex vivo as an integral tissue. HCMV infection triggered a rapid and robust decidual-tissue innate immune response predominated by interferon (IFN)γ and IP-10 induction, dysregulating the decidual cytokine/chemokine environment in a distinctive fashion. The decidual-tissue response was already elicited during viral-tissue contact, and was not affected by neutralizing HCMV antibodies. Of note, IFNγ induction, reflecting immune-cell activation, was distinctive to the maternal decidua, and was not observed in concomitantly-infected placental (fetal) villi. Our studies in a clinically-relevant surrogate human model, provide a novel insight into the first-line decidual tissue response which could affect the outcome of congenital infection.

  20. Psychoneuroimmunology in pregnancy: immune pathways linking stress with maternal health, adverse birth outcomes, and fetal development.

    PubMed

    Christian, Lisa M

    2012-01-01

    It is well-established that psychological stress promotes immune dysregulation in nonpregnant humans and animals. Stress promotes inflammation, impairs antibody responses to vaccination, slows wound healing, and suppresses cell-mediated immune function. Importantly, the immune system changes substantially to support healthy pregnancy, with attenuation of inflammatory responses and impairment of cell-mediated immunity. This adaptation is postulated to protect the fetus from rejection by the maternal immune system. Thus, stress-induced immune dysregulation during pregnancy has unique implications for both maternal and fetal health, particularly preterm birth. However, very limited research has examined stress-immune relationships in pregnancy. The application of psychoneuroimmunology research models to the perinatal period holds great promise for elucidating biological pathways by which stress may affect adverse pregnancy outcomes, maternal health, and fetal development.

  1. Psychoneuroimmunology in Pregnancy: Immune Pathways Linking Stress with Maternal Health, Adverse Birth Outcomes, and Fetal Development

    PubMed Central

    Christian, Lisa M.

    2011-01-01

    It is well-established that psychological stress promotes immune dysregulation in nonpregnant humans and animals. Stress promotes inflammation, impairs antibody responses to vaccination, slows wound healing, and suppresses cell-mediated immune function. Importantly, the immune system changes substantially to support healthy pregnancy, with attenuation of inflammatory responses and impairment of cell-mediated immunity. This adaptation is postulated to protect the fetus from rejection by the maternal immune system. Thus, stress-induced immune dysregulation during pregnancy has unique implications for both maternal and fetal health, particularly preterm birth. However, very limited research has examined stress-immune relationships in pregnancy. The application of psychoneuroimmunology research models to the perinatal period holds great promise for elucidating biological pathways by which stress may affect adverse pregnancy outcomes, maternal health, and fetal development. PMID:21787802

  2. Maternal Milk T Cells Drive Development of Transgenerational Th1 Immunity in Offspring Thymus.

    PubMed

    Ghosh, Mrinal K; Nguyen, Virginia; Muller, H Konrad; Walker, Ameae M

    2016-09-15

    Using multiple murine foster-nursing protocols, thereby eliminating placental transfer and allowing a distinction between dam- and pup-derived cells, we show that foster nursing by an immunized dam results in development of CD8(+) T cells in nonimmunized foster pups that are specific for Ags against which the foster dam was immunized (Mycobacterium tuberculosis or Candida albicans). We have dubbed this process "maternal educational immunity" to distinguish it from passive cellular immunity. Of the variety of maternal immune cells present in milk, only T cells were detected in pup tissues. Maternal T cells, a substantial percentage of which were CD4(+)MHC class II(+), accumulated in the pup thymus and spleen during the nursing period. Further analysis of maternal cells in the pup thymus showed that a proportion was positive for maternal immunogen-specific MHC class II tetramers. To determine the outcome of Ag presentation in the thymus, the maternal or foster pup origin of immunogen-responding CD8(+) cells in foster pup spleens was assessed. Whereas ∼10% were maternally derived in the first few weeks after weaning, all immunogen-responding CD8(+) T cells were pup derived by 12 wk of age. Pup-derived immunogen-responsive CD8(+) cells persisted until at least 1 y of age. Passive cellular immunity is well accepted and has been demonstrated in the human population. In this study, we show an arguably more important role for transferred immune cells: the direction of offspring T cell development. Harnessing maternal educational immunity through prepregnancy immunization programs has potential for improvement of infant immunity. PMID:27496970

  3. Effect of age and maternal antibodies on the systemic and mucosal immune response after neonatal immunization in a porcine model

    PubMed Central

    Guzman-Bautista, Edgar R; Garcia-Ruiz, Carlos E; Gama-Espinosa, Alicia L; Ramirez-Estudillo, Carmen; Rojas-Gomez, Oscar I; Vega-Lopez, Marco A

    2014-01-01

    Newborn mammals are highly susceptible to respiratory infections. Although maternal antibodies (MatAb) offer them some protection, they may also interfere with their systemic immune response to vaccination. However, the impact of MatAb on the neonatal mucosal immune response remains incompletely described. This study was performed to determine the effect of ovalbumin (OVA)-specific MatAb on the anti-OVA antibody response in sera, nasal secretions and saliva from specific pathogen-free Vietnamese miniature piglets immunized at 7 or 14 days of age. Our results demonstrated that MatAb increased antigen-specific IgA and IgG responses in sera, and transiently enhanced an early secretory IgA response in nasal secretions of piglets immunized at 7 days of age. In contrast, we detected a lower mucosal (nasal secretion and saliva) anti-OVA IgG response in piglets with MatAb immunized at 14 days of age, compared with piglets with no MatAb, suggesting a modulatory effect of antigen-specific maternal factors on the isotype transfer to the mucosal immune exclusion system. In our porcine model, we demonstrated that passive maternal immunity positively modulated the systemic and nasal immune responses of animals immunized early in life. Our results, therefore, open the possibility of inducing systemic and respiratory mucosal immunity in the presence of MatAb through early vaccination. PMID:24754050

  4. Physical activity, immunity and infection.

    PubMed

    Romeo, J; Wärnberg, J; Pozo, T; Marcos, A

    2010-08-01

    During the last few decades, scientific evidence has confirmed a wide range of health benefits related to regular physical activity. How physical activity affects the immune function and infection risk is, however, still under debate. Commonly, intensive exercise suppresses the activity and levels of several immune cells, while other immune functions may be stimulated by moderate physical activity. With this knowledge, the understanding of the relationship between different levels of physical activity on the immune function has been raised as a potential tool to protect health not only in athletes but also in the general population; the mechanisms that translate a physically active lifestyle into good health continue to be investigated. Reviewing the literature, although several outcomes (i.e. the mechanisms by which different levels and duration of physical activity programmes affect numerous cell types and responses) remain unclear, given that the additional benefits encompass healthy habits including exercise, the use of physical activity programmes may result in improved health of elderly populations. Moderate physical activity or moderate-regulated training may enhance the immune function mainly in less fit subjects or sedentary population and the pre-event fitness status also seems to be an important individual factor regarding this relationship. Although adequate nutrition and regular physical activity habits may synergistically improve health, clinical trials in athletes using nutritional supplements to counteract the immune suppression have been inconclusive so far.Further research is necessary to find out to what extent physical activity training can exert an effect on the immune function.

  5. Maternal Milk T Cells Drive Development of Transgenerational Th1 Immunity in Offspring Thymus

    PubMed Central

    Ghosh, Mrinal K.; Nguyen, Virginia; Muller, H. Konrad

    2016-01-01

    Using multiple murine foster-nursing protocols, thereby eliminating placental transfer and allowing a distinction between dam- and pup-derived cells, we show that foster nursing by an immunized dam results in development of CD8+ T cells in nonimmunized foster pups that are specific for Ags against which the foster dam was immunized (Mycobacterium tuberculosis or Candida albicans). We have dubbed this process “maternal educational immunity” to distinguish it from passive cellular immunity. Of the variety of maternal immune cells present in milk, only T cells were detected in pup tissues. Maternal T cells, a substantial percentage of which were CD4+MHC class II+, accumulated in the pup thymus and spleen during the nursing period. Further analysis of maternal cells in the pup thymus showed that a proportion was positive for maternal immunogen-specific MHC class II tetramers. To determine the outcome of Ag presentation in the thymus, the maternal or foster pup origin of immunogen-responding CD8+ cells in foster pup spleens was assessed. Whereas ∼10% were maternally derived in the first few weeks after weaning, all immunogen-responding CD8+ T cells were pup derived by 12 wk of age. Pup-derived immunogen-responsive CD8+ cells persisted until at least 1 y of age. Passive cellular immunity is well accepted and has been demonstrated in the human population. In this study, we show an arguably more important role for transferred immune cells: the direction of offspring T cell development. Harnessing maternal educational immunity through prepregnancy immunization programs has potential for improvement of infant immunity. PMID:27496970

  6. Immune mechanisms at the maternal-fetal interface: perspectives and challenges

    PubMed Central

    PrabhuDas, Mercy; Bonney, Elizabeth; Caron, Kathleen; Dey, Sudhansu; Erlebacher, Adrian; Fazleabas, Asgerally; Fisher, Susan; Golos, Thaddeus; Matzuk, Martin; McCune, Joseph M; Mor, Gil; Schulz, Laura; Soares, Michael; Spencer, Thomas; Strominger, Jack; Way, Sing Sing; Yoshinaga, Koji

    2016-01-01

    Leaders gathered at the US National Institutes of Health in November 2014 to discuss recent advances and emerging research areas in aspects of maternal-fetal immunity that may affect fetal development and pregnancy success. PMID:25789673

  7. Maternal Immune-Mediated Conditions, Autism Spectrum Disorders, and Developmental Delay

    ERIC Educational Resources Information Center

    Lyall, Kristen; Ashwood, Paul; Van de Water, Judy; Hertz-Picciotto, Irva

    2014-01-01

    The maternal immune system may play a role in offspring neurodevelopment. We examined whether maternal autoimmune disease, asthma, and allergy were associated with child autism spectrum disorder (ASD) and developmental delay without autism (DD) using 560 ASD cases, 391 typically developing controls, and 168 DD cases from the CHildhood Autism Risk…

  8. Maternal fatty acid desaturase genotype correlates with infant immune responses at 6 months.

    PubMed

    Muc, Magdalena; Kreiner-Møller, Eskil; Larsen, Jeppe M; Birch, Sune; Brix, Susanne; Bisgaard, Hans; Lauritzen, Lotte

    2015-09-28

    Breast milk long-chain PUFA (LCPUFA) have been associated with changes in early life immune responses and may modulate T-cell function in infancy. We studied the effect of maternal fatty acid desaturase (FADS) genotype and breast milk LCPUFA levels on infants' blood T-cell profiles and ex vivo-produced cytokines after anti-CD3/CD28 stimulation of peripheral blood mononuclear cells in 6-month-old infants from the Copenhagen Prospective Study of Asthma in Childhood birth cohort. LCPUFA concentrations of breast milk were assessed at 4 weeks of age, and FADS SNP were determined in both mothers and infants (n 109). In general, breast milk arachidonic acid (AA) levels were inversely correlated with the production of IL-10 (r -0.25; P=0.004), IL-17 (r -0.24; P=0.005), IL-5 (r -0.21; P=0.014) and IL-13 (r -0.17; P=0.047), whereas EPA was positively correlated with the counts of blood regulatory T-cells and cytotoxic T-cells and decreased T-helper cell counts. The minor FADS alleles were associated with lower breast milk AA and EPA, and infants of mothers carrying the minor allele of FADS SNP rs174556 had higher production of IL-10 (r -0.23; P=0.018), IL-17 (r -0.25; P=0.009) and IL-5 (r -0.21; P=0.038) from ex vivo-activated immune cells. We observed no association between T-cell distribution and maternal or infant FADS gene variants. We conclude that increased maternal LCPUFA synthesis and breast milk AA are associated with decreased levels of IL-5, IL-13 (type-2 related), IL-17 (type-17 related) and IL-10 (regulatory immune responses), but not with interferon-γ and TNF-α, which could be due to an effect of the maternal FADS variants on the offspring immune response transferred via breast milk LCPUFA. PMID:26283408

  9. Protein Nutrition of Southern Plains Small Mammals: Immune Response to Variation in Maternal and Offspring Dietary Nitrogen

    EPA Science Inventory

    Maternal nutrition during pregnancy and postnatal offspring nutrition may influence offspring traits. We investigated the effects of maternal and postweaning offspring dietary nitrogen on immune function and hematology in two species of rodent: the hispid cotton rat (Sigmodon his...

  10. Maternal alloantibodies induce a postnatal immune response that limits engraftment following in utero hematopoietic cell transplantation in mice

    PubMed Central

    Merianos, Demetri J.; Tiblad, Eleonor; Santore, Matthew T.; Todorow, Carlyn A.; Laje, Pablo; Endo, Masayuki; Zoltick, Philip W.; Flake, Alan W.

    2009-01-01

    The lack of fetal immune responses to foreign antigens, i.e., fetal immunologic tolerance, is the most compelling rationale for prenatal stem cell and gene therapy. However, the frequency of engraftment following in utero hematopoietic cell transplantation (IUHCT) in the murine model is reduced in allogeneic, compared with congenic, recipients. This observation supports the existence of an immune barrier to fetal transplantation and challenges the classic assumptions of fetal tolerance. Here, we present evidence that supports the presence of an adaptive immune response in murine recipients of IUHCT that failed to maintain engraftment. However, when IUHCT recipients were fostered by surrogate mothers, they all maintained long-term chimerism. Furthermore, we have demonstrated that the cells responsible for rejection of the graft were recipient in origin. Our observations suggest a mechanism by which IUHCT-dependent sensitization of the maternal immune system and the subsequent transmission of maternal alloantibodies to pups through breast milk induces a postnatal adaptive immune response in the recipient, which, in turn, results in the ablation of engraftment after IUHCT. Finally, we showed that non-fostered pups that maintained their chimerism had higher levels of Tregs as well as a more suppressive Treg phenotype than their non-chimeric, non-fostered siblings. This study resolves the apparent contradiction of induction of an adaptive immune response in the pre-immune fetus and confirms the potential of actively acquired tolerance to facilitate prenatal therapeutic applications. PMID:19652363

  11. The Contribution of the Maternal Immune System to the Establishment of Pregnancy in Cattle

    PubMed Central

    Fair, Trudee

    2014-01-01

    Immune cells play an integral role in affecting successful reproductive function. Indeed, disturbed or aberrant immune function has been identified as primary mechanisms behind infertility. In contrast to the extensive body of literature that exists for human and mouse, studies detailing the immunological interaction between the embryo and the maternal endometrium are quite few in cattle. Nevertheless, by reviewing the existing studies and extrapolating from sheep, pig, mouse, and human data, we can draw a reasonably comprehensive picture. Key contributions of immune cell populations include granulocyte involvement in follicle differentiation and gamete transfer, monocyte invasion of the peri-ovulatory follicle and their subsequent role in corpus luteum formation and the pivotal roles of maternal macrophage and dendritic cells in key steps of the establishment of pregnancy, particularly, the maternal immune response to the embryo. These contributions are reviewed in detail below and key findings are discussed. PMID:25674085

  12. Maternal Antibodies: Clinical Significance, Mechanism of Interference with Immune Responses, and Possible Vaccination Strategies

    PubMed Central

    Niewiesk, Stefan

    2014-01-01

    Neonates have an immature immune system, which cannot adequately protect against infectious diseases. Early in life, immune protection is accomplished by maternal antibodies transferred from mother to offspring. However, decaying maternal antibodies inhibit vaccination as is exemplified by the inhibition of seroconversion after measles vaccination. This phenomenon has been described in both human and veterinary medicine and is independent of the type of vaccine being used. This review will discuss the use of animal models for vaccine research. I will review clinical solutions for inhibition of vaccination by maternal antibodies, and the testing and development of potentially effective vaccines. These are based on new mechanistic insight about the inhibitory mechanism of maternal antibodies. Maternal antibodies inhibit the generation of antibodies whereas the T cell response is usually unaffected. B cell inhibition is mediated through a cross-link between B cell receptor (BCR) with the Fcγ-receptor IIB by a vaccine–antibody complex. In animal experiments, this inhibition can be partially overcome by injection of a vaccine-specific monoclonal IgM antibody. IgM stimulates the B cell directly through cross-linking the BCR via complement protein C3d and antigen to the complement receptor 2 (CR2) signaling complex. In addition, it was shown that interferon alpha binds to the CD21 chain of CR2 as well as the interferon receptor and that this dual receptor usage drives B cell responses in the presence of maternal antibodies. In lieu of immunizing the infant, the concept of maternal immunization as a strategy to protect neonates has been proposed. This approach would still not solve the question of how to immunize in the presence of maternal antibodies but would defer the time of infection to an age where infection might not have such a detrimental outcome as in neonates. I will review successful examples and potential challenges of implementing this concept. PMID

  13. Molecular Mechanisms and Timing of Cortical Immune Activation in Schizophrenia

    PubMed Central

    Volk, David W.; Chitrapu, Anjani; Edelson, Jessica R.; Roman, Kaitlyn M.; Moroco, Annie E.; Lewis, David A.

    2016-01-01

    Objective Immune-related abnormalities are commonly reported in schizophrenia, including higher mRNA levels for the viral restriction factor interferon-induced transmembrane protein (IFITM) in the prefrontal cortex. The authors sought to clarify whether higher IFITM mRNA levels and other immune-related disturbances in the prefrontal cortex are the consequence of an ongoing molecular cascade contributing to immune activation or the reflection of a long-lasting maladaptive response to an in utero immune-related insult. Method Quantitative polymerase chain reaction was employed to measure mRNA levels for immune-related cytokines and transcriptional regulators, including those reported to regulate IFITM expression, in the prefrontal cortex from 62 schizophrenia and 62 healthy subjects and from adult mice exposed prenatally to maternal immune activation or in adulthood to the immune stimulant poly(I:C). Results Schizophrenia subjects had markedly higher mRNA levels for interleukin 6 (IL-6) (+379%) and interferon-β (+29%), which induce IFITM expression; lower mRNA levels for Schnurri-2 (−10%), a transcriptional inhibitor that lowers IFITM expression; and higher mRNA levels for nuclear factor-κB (+86%), a critical transcription factor that mediates cytokine regulation of immune-related gene expression. In adult mice that received daily poly(I:C) injections, but not in offspring with prenatal exposure to maternal immune activation, frontal cortex mRNA levels were also markedly elevated for IFITM (+304%), multiple cytokines including IL-6 (+493%), and nuclear factor-κB (+151%). Conclusions These data suggest that higher prefrontal cortex IFITM mRNA levels in schizophrenia may be attributable to adult, but not prenatal, activation of multiple immune markers and encourage further investigation into the potential role of these and other immune markers as therapeutic targets in schizophrenia. PMID:26133963

  14. The interaction between maternal stress and the ontogeny of the innate immune system during teleost embryogenesis: implications for aquaculture practice.

    PubMed

    Li, M; Leatherland, J F

    2012-11-01

    The barrier defences and acellular innate immune proteins play critical roles during the early-stage fish embryos prior to the development of functional organ systems. The innate immune proteins in the yolk of embryos are of maternal origin. Maternal stress affects the maternal-to-embryo transfer of these proteins and, therefore, environmental stressors may change the course of embryo development, including embryonic immunocompetency, via their deleterious effect on maternal physiology. This review focuses on the associations that exist between maternal stress, maternal endocrine disturbance and the responses of the acellular innate immune proteins of early-stage fish embryos. Early-stage teleostean embryos are dependent upon the adult female for the formation of the zona pellucida as an essential barrier defence, for their supply of nutrients, and for the innate immunity proteins and antibodies that are transferred from the maternal circulation to the oocytes; maternally derived hormones are also transferred, some of which (such as cortisol) are known to exert a suppressive action on some aspects of the immune defences. This review summarizes what is known about the effects of oocyte cortisol content on the immune system components in early embryos. The review also examines recent evidence that embryonic cells during early cleavage have the capacity to respond to increased maternal cortisol transfer; this emphasizes the importance of maternal and early immune competence on the later life of fishes, both in the wild and in intensive culture.

  15. Group B Streptococcus vaccination in pregnancy: moving toward a global maternal immunization program.

    PubMed

    Munoz, Flor M; Ferrieri, Patricia

    2013-08-28

    A group B streptococcus vaccine for pregnant women would add to the currently available vaccines given during pregnancy to protect mothers and their infants against serious and potentially lethal diseases, including tetanus, influenza, pertussis and meningococcal infection. Implementation of the administration of these high priority vaccines during routine prenatal care would result in a maternal immunization program with the potential to have a positive impact in public health globally, by reducing maternal and neonatal morbidity and mortality.

  16. The impact of maternally derived immunity on influenza A virus transmission in neonatal pig populations.

    PubMed

    Allerson, Matt; Deen, John; Detmer, Susan E; Gramer, Marie R; Joo, Han Soo; Romagosa, Anna; Torremorell, Montserrat

    2013-01-01

    The commonality of influenza A virus (IAV) exposure and vaccination on swine farms in the United States ensures that the majority of neonatal pigs will have some degree of maternal immunity to IAV. The influence of maternal immunity on IAV transmission in neonatal pig populations will impact virus prevalence and infection dynamics across pig populations. The main objective of this study was to assess the impact of maternally derived immunity on IAV transmission in an experimental setting. Neonatal pigs suckled colostrum and derived maternal (passive) immunity from sows in one of three treatment groups: (a) non-vaccinated control (CTRL) or vaccinated with (b) homologous (PASSV-HOM) or (c) heterologous (PASSV-HET) inactivated experimental IAV vaccines. Sentinel neonatal pigs derived from the groups above were challenged with IAV via direct contact with an experimentally infected pig (seeder pig) and monitored for IAV infection daily via nasal swab sampling. A susceptible-infectious-recovered (SIR) experimental model was used to obtain and estimate transmission parameters in each treatment group via a generalized linear model. All sentinel pigs in the CTRL (30/30) and PASSV-HET (30/30) groups were infected with IAV following contact with the seeder pigs and the reproduction ratio estimates (95% confidence interval) were 10.4 (6.6-15.8) and 7.1 (4.2-11.3), respectively. In contrast, 1/20 sentinel pigs in the PASSV-HOM group was infected following contact with the seeder pigs and the reproduction ratio estimate was significantly lower compared to the CTRL and PASSV-HET groups at 0.8 (0.1-3.7). Under the conditions of this study, IAV transmission was reduced in neonatal pigs with homologous maternal immunity compared to seronegative neonatal pigs and pigs with heterologous maternal immunity as defined in this study. This study provides estimates for IAV transmission in pigs with differing types of maternal immunity which may describe the influence of maternal immunity on

  17. Innate Immune Activation in Obesity

    PubMed Central

    Lumeng, Carey N.

    2014-01-01

    The innate immune system is a prewired set of cellular and humoral components that has developed to sense perturbations in normal physiology and trigger responses to restore the system back to baseline. It is now understood that many of these components can also sense the physiologic changes that occur with obesity and be activated. While the exact reasons for this chronic immune response to obesity are unclear, there is strong evidence to suggest that innate inflammatory systems link obesity and disease. Based on this, anti-inflammatory therapies for diseases like type 2 diabetes and metabolic syndrome may form the core of future treatment plans. This review will highlight the components involved in the innate immune response and discuss the evidence that they contribute to the pathogenesis of obesity-associated diseases. PMID:23068074

  18. Maternal antibody transfer can lead to suppression of humoral immunity in developing zebra finches (Taeniopygia guttata).

    PubMed

    Merrill, Loren; Grindstaff, Jennifer L

    2014-01-01

    Maternally transferred antibodies have been documented in a wide range of taxa and are thought to adaptively provide protection against parasites and pathogens while the offspring immune system is developing. In most birds, transfer occurs when females deposit immunoglobulin Y into the egg yolk, and it is proportional to the amount in the female's plasma. Maternal antibodies can provide short-term passive protection as well as specific and nonspecific immunological priming, but high levels of maternal antibody can result in suppression of the offspring's humoral immune response. We injected adult female zebra finches (Taeniopygia guttata) with one of two antigens (lipopolysaccharide [LPS] or keyhole limpet hemocyanin [KLH]) or a control and then injected offspring with LPS, KLH, or a control on days 5 and 28 posthatch to examine the impact of maternally transferred antibodies on the ontogeny of the offspring's humoral immune system. We found that offspring of females exposed to KLH had elevated levels of KLH-reactive antibody over the first 17-28 days posthatch but reduced KLH-specific antibody production between days 28 and 36. We also found that offspring exposed to either LPS or KLH exhibited reduced total antibody levels, compared to offspring that received a control injection. These results indicate that high levels of maternal antibodies or antigen exposure during development can have negative repercussions on short-term antibody production and may have long-term fitness repercussions for the offspring.

  19. Drug treatment of malaria infections can reduce levels of protection transferred to offspring via maternal immunity

    PubMed Central

    Staszewski, Vincent; Reece, Sarah E.; O'Donnell, Aidan J.; Cunningham, Emma J. A.

    2012-01-01

    Maternally transferred immunity can have a fundamental effect on the ability of offspring to deal with infection. However, levels of antibodies in adults can vary both quantitatively and qualitatively between individuals and during the course of infection. How infection dynamics and their modification by drug treatment might affect the protection transferred to offspring remains poorly understood. Using the rodent malaria parasite Plasmodium chabaudi, we demonstrate that curing dams part way through infection prior to pregnancy can alter their immune response, with major consequences for offspring health and survival. In untreated maternal infections, maternally transferred protection suppressed parasitaemia and reduced pup mortality by 75 per cent compared with pups from naïve dams. However, when dams were treated with anti-malarial drugs, pups received fewer maternal antibodies, parasitaemia was only marginally suppressed, and mortality risk was 25 per cent higher than for pups from dams with full infections. We observed the same qualitative patterns across three different host strains and two parasite genotypes. This study reveals the role that within-host infection dynamics play in the fitness consequences of maternally transferred immunity. Furthermore, it highlights a potential trade-off between the health of mothers and offspring suggesting that anti-parasite treatment may significantly affect the outcome of infection in newborns. PMID:22357264

  20. Maternal natural source vitamin E supplementation on suckling calf performance and immune response

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to determine the effects of maternally supplemented natural-source vitamin E (NSVE) on suckling calf performance and immune response. In a two-year study, one hundred twenty-five Angus-cross beef cows (n = 75/year one, 50/year two) initial BW = 607 kg; initial BCS = 5...

  1. Maternal Immune-Mediated Conditions, Autism Spectrum Disorders, and Developmental Delay

    PubMed Central

    Ashwood, Paul; Van de Water, Judy; Hertz-Picciotto, I.

    2014-01-01

    The maternal immune system may play a role in offspring neurodevelopment. We examined whether maternal autoimmune disease, asthma, and allergy were associated with child autism spectrum disorder (ASD) and developmental delay without autism (DD) using 560 ASD cases, 391 typically developing controls, and 168 DD cases from the CHildhood Autism Risk from Genetics and the Environment (CHARGE) study. Results from conditional logistic regression demonstrated few significant associations overall. Maternal autoimmune disease was significantly associated with a modest increase in odds of developmental disorders (combined ASD + DD; OR = 1.46, 95 % CI 1.01, 2.09) but not of ASD alone. Associations with certain allergens and onset periods were also suggested. These findings suggest maternal autoimmune disease may modestly influence childhood developmental disorders (ASD + DD). PMID:24337796

  2. Regulatory T cells, maternal-foetal immune tolerance and recurrent miscarriage: new therapeutic challenging opportunities.

    PubMed

    Alijotas-Reig, Jaume; Melnychuk, Taisiia; Gris, Josep Maria

    2015-03-15

    Because maternal alloreactive lymphocytes are not depleted during pregnancy, local and/or systemic mechanisms have to play a key role in altering the maternal immune response. Peripheral T regulatory cells (pTregs) at the maternal-foetal interface are necessary in situ to prevent early abortion, but only those pTregs that have been previously exposed to paternal alloantigens. It has been showed that pregnancy selectively stimulates the accumulation of maternal Foxp3(+)CD4(+)CD25(+) (Foxp3Tregs) cells with foetal specificity. Interestingly, after delivery, foetal-specific pTregs persist at elevated levels, maintain tolerance to pre-existing foetal antigen, and rapidly re-accumulate during subsequent pregnancy. pTreg up-regulation could be hypothesized as a possible future therapeutic strategy in humans.

  3. Immune function across generations: integrating mechanism and evolutionary process in maternal antibody transmission.

    PubMed Central

    Grindstaff, Jennifer L; Brodie, Edmund D; Ketterson, Ellen D

    2003-01-01

    The past 30 years of immunological research have revealed much about the proximate mechanisms of maternal antibody transmission and utilization, but have not adequately addressed how these issues are related to evolutionary and ecological theory. Much remains to be learned about individual differences within a species in maternal antibody transmission as well as differences among species in transmission or utilization of antibodies. Similarly, maternal-effects theory has generally neglected the mechanisms by which mothers influence offspring phenotype. Although the environmental cues that generate maternal effects and the consequent effects for offspring phenotype are often well characterized, the intermediary physiological and developmental steps through which the maternal effect is transmitted are generally unknown. Integration of the proximate mechanisms of maternal antibody transmission with evolutionary theory on maternal effects affords an important opportunity to unite mechanism and process by focusing on the links between genetics, environment and physiology, with the ultimate goal of explaining differences among individuals and species in the transfer of immune function from one generation to the next. PMID:14667346

  4. Three randomized trials of maternal influenza immunization in Mali, Nepal, and South Africa: Methods and expectations.

    PubMed

    Omer, Saad B; Richards, Jennifer L; Madhi, Shabir A; Tapia, Milagritos D; Steinhoff, Mark C; Aqil, Anushka R; Wairagkar, Niteen

    2015-07-31

    Influenza infection in pregnancy can have adverse impacts on maternal, fetal, and infant outcomes. Influenza vaccination in pregnancy is an appealing strategy to protect pregnant women and their infants. The Bill & Melinda Gates Foundation is supporting three large, randomized trials in Nepal, Mali, and South Africa evaluating the efficacy and safety of maternal immunization to prevent influenza disease in pregnant women and their infants <6 months of age. Results from these individual studies are expected in 2014 and 2015. While the results from the three maternal immunization trials are likely to strengthen the evidence base regarding the impact of influenza immunization in pregnancy, expectations for these results should be realistic. For example, evidence from previous influenza vaccine studies - conducted in general, non-pregnant populations - suggests substantial geographic and year-to-year variability in influenza incidence and vaccine efficacy/effectiveness. Since the evidence generated from the three maternal influenza immunization trials will be complementary, in this paper we present a side-by-side description of the three studies as well as the similarities and differences between these trials in terms of study location, design, outcome evaluation, and laboratory and epidemiological methods. We also describe the likely remaining knowledge gap after the results from these trials become available along with a description of the analyses that will be conducted when the results from these individual data are pooled. Moreover, we highlight that additional research on logistics of seasonal influenza vaccine supply, surveillance and strain matching, and optimal delivery strategies for pregnant women will be important for informing global policy related to maternal influenza immunization.

  5. Maternal body size influences offspring immune configuration in an oviparous snake

    PubMed Central

    Brown, Gregory P.

    2016-01-01

    Like most ectothermic vertebrates, keelback snakes (Tropidonophis mairii) do not exhibit parental care. Thus, offspring must possess an immune system capable of dealing with challenges such as pathogens, without assistance from an attendant parent. We know very little about immune system characteristics of neonatal reptiles, including the magnitude of heritability and other maternal influences. To identify sources of variation in circulating white blood cell (WBC) concentrations and differentials, we examined blood smears from 246 hatchling snakes and their field-caught mothers. WBC concentrations were lower in hatchlings than in adults, and hatchlings had more basophils and fewer azurophils than adults. A hatchling keelback's WBC differential was also influenced by its sex and body size. Although hatchling WBC measures exhibited negligible heritability, they were strongly influenced by maternal body size and parasite infection (but not by maternal body condition, relative clutch mass or time in captivity). Larger mothers produced offspring with more azurophils and fewer lymphocytes. The mechanisms and consequences of WBC variation are currently unknown, but if these maternal effects enhance offspring fitness, the impact of maternal body size on reproductive success may be greater than expected simply from allometric increases in the numbers and sizes of progeny. PMID:27069670

  6. Maternal body size influences offspring immune configuration in an oviparous snake.

    PubMed

    Brown, Gregory P; Shine, Richard

    2016-03-01

    Like most ectothermic vertebrates, keelback snakes (Tropidonophis mairii) do not exhibit parental care. Thus, offspring must possess an immune system capable of dealing with challenges such as pathogens, without assistance from an attendant parent. We know very little about immune system characteristics of neonatal reptiles, including the magnitude of heritability and other maternal influences. To identify sources of variation in circulating white blood cell (WBC) concentrations and differentials, we examined blood smears from 246 hatchling snakes and their field-caught mothers. WBC concentrations were lower in hatchlings than in adults, and hatchlings had more basophils and fewer azurophils than adults. A hatchling keelback's WBC differential was also influenced by its sex and body size. Although hatchling WBC measures exhibited negligible heritability, they were strongly influenced by maternal body size and parasite infection (but not by maternal body condition, relative clutch mass or time in captivity). Larger mothers produced offspring with more azurophils and fewer lymphocytes. The mechanisms and consequences of WBC variation are currently unknown, but if these maternal effects enhance offspring fitness, the impact of maternal body size on reproductive success may be greater than expected simply from allometric increases in the numbers and sizes of progeny. PMID:27069670

  7. Transfer of Maternal Immune Cells by Breastfeeding: Maternal Cytotoxic T Lymphocytes Present in Breast Milk Localize in the Peyer’s Patches of the Nursed Infant

    PubMed Central

    Tang, May; Zumba, Osvaldo; Mehta, Hetali; Toma, Annmarie; Sant’Angelo, Derek; Laouar, Yasmina

    2016-01-01

    Despite our knowledge of the protective role of antibodies passed to infants through breast milk, our understanding of immunity transfer via maternal leukocytes is still limited. To emulate the immunological interface between the mother and her infant while breast-feeding, we used murine pups fostered after birth onto MHC-matched and MHC-mismatched dams. Overall, data revealed that: 1) Survival of breast milk leukocytes in suckling infants is possible, but not significant after the foster-nursing ceases; 2) Most breast milk lymphocytes establish themselves in specific areas of the intestine termed Peyer’s patches (PPs); 3) While most leukocytes in the milk bolus were myeloid cells, the majority of breast milk leukocytes localized to PPs were T lymphocytes, and cytotoxic T cells (CTLs) in particular; 4) These CTLs exhibit high levels of the gut-homing molecules α4β7 and CCR9, but a reduced expression of the systemic homing marker CD62L; 5) Under the same activation conditions, transferred CD8 T cells through breast milk have a superior capacity to produce potent cytolytic and inflammatory mediators when compared to those generated by the breastfed infant. It is therefore possible that maternal CTLs found in breast milk are directed to the PPs to compensate for the immature adaptive immune system of the infant in order to protect it against constant oral infectious risks during the postnatal phase. PMID:27285085

  8. Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity

    NASA Astrophysics Data System (ADS)

    van de Pavert, Serge A.; Ferreira, Manuela; Domingues, Rita G.; Ribeiro, Hélder; Molenaar, Rosalie; Moreira-Santos, Lara; Almeida, Francisca F.; Ibiza, Sales; Barbosa, Inês; Goverse, Gera; Labão-Almeida, Carlos; Godinho-Silva, Cristina; Konijn, Tanja; Schooneman, Dennis; O'Toole, Tom; Mizee, Mark R.; Habani, Yasmin; Haak, Esther; Santori, Fabio R.; Littman, Dan R.; Schulte-Merker, Stefan; Dzierzak, Elaine; Simas, J. Pedro; Mebius, Reina E.; Veiga-Fernandes, Henrique

    2014-04-01

    The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor RORγt. Accordingly, enforced expression of Rorgt restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring.

  9. Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity

    PubMed Central

    van de Pavert, Serge A.; Ferreira, Manuela; Domingues, Rita G.; Ribeiro, Hélder; Molenaar, Rosalie; Moreira-Santos, Lara; Almeida, Francisca F.; Ibiza, Sales; Barbosa, Inês; Goverse, Gera; Labão-Almeida, Carlos; Godinho-Silva, Cristina; Konijn, Tanja; Schooneman, Dennis; O’Toole, Tom; Mizee, Mark R.; Habani, Yasmin; Haak, Esther; Santori, Fabio R.; Littman, Dan R.; Schulte-Merker, Stefan; Dzierzak, Elaine; Simas, J. Pedro; Mebius, Reina E.; Veiga-Fernandes, Henrique

    2016-01-01

    The impact of the nutritional status during foetal life in the overall health of adults has been recognised1. However dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs (SLOs) occurs during embryogenesis and is considered to be developmentally programmed2,3. SLO formation dependents on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells2,3,4,5. Here we show that foetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero pre-setting the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi differentiation was controlled by maternal retinoid intake and foetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor RORγt. Accordingly, enforced expression of Rorgt restored maturation of LTi cells with impaired RA signalling, while RA receptors directly regulated the Rorc locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring. PMID:24670648

  10. Neonatal Immunization with Respiratory Syncytial Virus Glycoprotein Fragment Induces Protective Immunity in the Presence of Maternal Antibodies in Mice

    PubMed Central

    Noh, Youran; Shim, Byoung-Shik; Cheon, In Su; Rho, Semi; Kim, Hee Joo; Choi, Youngjoo; Kang, Chang-Yuil; Chang, Jun

    2013-01-01

    Abstract Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants and the elderly worldwide. The significant morbidity and mortality associated with this infection underscores the urgent need for development of RSV vaccine. In this study, we first show that intranasal administration of RSV glycoprotein core fragment (Gcf) to neonatal mice can induce systemic humoral immune responses and protective immunity against RSV without causing lung eosinophilia, although antibody response was shifted to a Th2 response. Next, we examined whether the presence of maternal anti-RSV antibodies would affect the responsiveness and protection efficacy of Gcf in newborn mice, since infants can possess RSV-specific maternal antibodies due to frequent RSV re-infections to adults. Intranasal administration of Gcf induced antibody response and increased IFNγ secretion and protected mice against RSV challenge without severe lung eosinophilia, even in the presence of high levels of RSV-specific maternal antibodies. Thus, our findings suggest that Gcf may be an effective and safe RSV vaccine during the neonatal period. PMID:23869549

  11. Differential expression and costs between maternally and paternally derived immune priming for offspring in an insect.

    PubMed

    Zanchi, Caroline; Troussard, Jean-Philippe; Martinaud, Guillaume; Moreau, Jérôme; Moret, Yannick

    2011-11-01

    1. When parasitized, both vertebrates and invertebrates can enhance the immune defence of their offspring, although this transfer of immunity is achieved by different mechanisms. In some insects, immune-challenged males can also initiate trans-generational immune priming (TGIP), but its expressions appear qualitatively different from the one induced by females similarly challenged. 2. The existence of male TGIP challenges the traditional view of the parental investment theory, which predicts that females should invest more into their progeny than males. However, sexual dimorphism in life-history strategies and the potential costs associated with TGIP may nevertheless lead to dissymmetric investment between males and females into the immune protection of the offspring. 3. Using the yellow mealworm beetle, Tenebrio molitor, we show that after parental exposure to a bacterial-like infection, maternal and paternal TGIP are associated with the enhancement of different immune effectors and different fitness costs in the offspring. While all the offspring produced by challenged mothers had enhanced immune defence, only those from early reproductive episodes were immune primed by challenged fathers. 4. Despite the fact that males and females may share a common interest in providing their offspring with an immune protection from the current pathogenic threat, they seem to have evolved different strategies concerning this investment. PMID:21644979

  12. Perceived Maternal Role Competence among the Mothers Attending Immunization Clinics of Dharan, Nepal

    PubMed Central

    Shrooti, Shah; Mangala, Shrestha; Nirmala, Pokharel; Devkumari, Shrestha; Dharanidhar, Baral

    2016-01-01

    Background: Being a mother is considered by many women as their most important role in life. Women’s perceptions of their abilities to manage the demands of parenting and the parenting skills they posses are reflected by perceived maternal role competence. The present study was carried out to assess the perceived maternal role competence and its associated factors among mothers. Methods: A descriptive cross-sectional research study was carried out on 290 mothers of infant in four immunization clinics of Dharan, Nepal. Data were collected using a standardized predesigned, pretested questionnaire (Parent sense of competence scale, Rosenberg’s self esteem scale, Maternity social support scale). The data were analyzed using descriptive and inferential statistics and multiple regression analysis at 0.05 level of significance. Results: The mean score of the perceived maternal role competence obtained by mothers was 64.34±7.90 and those of knowledge/skill and valuing/comfort subscale were 31±6.01 and 33±3.75, respectively. There was a significant association between perceived maternal role competence and factors as the age of the mother (P<0.001), educational status (P=0.015), occupation (P=0.001) and readiness for pregnancy (P=0.022). The study findings revealed a positive correlation between perceived maternal role competence and age at marriage (r=0.132, P=0.024), per capita income (r=0.118, P=0.045), self esteem (r=0.379, P<0.001), social support (r=0.272, P<0.001), and number of support persons (r=0.119, P=0.043). The results of the step wise multiple regression analysis revealed that the major predictor of perceived maternal role competence was self esteem. Conclusion: The factors associated with perceived maternal role competence were age, education, occupation, per capita income, self esteem, social support, and the number of support persons. PMID:27218107

  13. Prenatal maternal immune disruption and sex-dependent risk for psychoses

    PubMed Central

    Goldstein, J. M; Cherkerzian, S.; Seidman, L. J.; Donatelli, J.-A. L.; Remington, A. G.; Tsuang, M. T.; Hornig, M.; Buka, S. L.

    2015-01-01

    Background Previous studies suggest that abnormalities in maternal immune activity during pregnancy alter the offspring’s brain development and are associated with increased risk for schizophrenia (SCZ) dependent on sex. Method Using a nested case–control design and prospectively collected prenatal maternal sera from which interleukin (IL)-1β, IL-8, IL-6, tumor necrosis factor (TNF)-α and IL-10 were assayed, we investigated sex-dependent associations between these cytokines and 88 psychotic cases [SCZ=44; affective psychoses (AP)=44] and 100 healthy controls from a pregnancy cohort followed for >40 years. Analyses included sex-stratified non-parametric tests adjusted for multiple comparisons to screen cytokines associated with SCZ risk, followed by deviant subgroup analyses using generalized estimating equation (GEE) models. Results There were higher prenatal IL-6 levels among male SCZ than male controls, and lower TNF-α levels among female SCZ than female controls. The results were supported by deviant subgroup analyses with significantly more SCZ males with high IL-6 levels (>highest quartile) compared with controls [odd ratio (OR)75=3.33, 95% confidence interval (CI) 1.13–9.82], and greater prevalence of low TNF-α levels (

  14. PGRP-LB is a maternally transmitted immune milk protein that influences symbiosis and parasitism in tsetse’s offspring

    PubMed Central

    Wang, Jingwen; Aksoy, Serap

    2012-01-01

    Beneficial microbe functions range from host dietary supplementation to development and maintenance of host immune system. In mammals, newborn progeny are quickly colonized with a symbiotic fauna that is provisioned in mother’s milk and that closely resembles that of the parent. Tsetse fly (Diptera: Glossinidae) also depends on the obligate symbiont Wigglesworthia for nutritional supplementation, optimal fecundity, and immune system development. Tsetse progeny develop one at a time in an intrauterine environment and receive nourishment and symbionts in mother’s milk. We show that the host Peptidoglycan Recognition Protein (PGRP-LB) is expressed only in adults and is a major component of the milk that nourishes the developing progeny. The amidase activity associated with PGRP-LB may scavenge the symbiotic peptidoglycan and prevent the induction of tsetse's Immune Deficiency pathway that otherwise can damage the symbionts. Reduction of PGRP-LB experimentally diminishes female fecundity and damages Wigglesworthia in the milk through induction of antimicrobial peptides, including Attacin. Larvae that receive less maternal PGRP-LB give rise to adults with fewer Wigglesworthia and hyperimmune responses. Such adults also suffer dysregulated immunity, as indicated by the presence of higher trypanosome densities in parasitized adults. We show that recPGRP-LB has antimicrobial and antitrypanosomal activities that may regulate symbiosis and impact immunity. Thus, PGRP-LB plays a pivotal role in tsetse’s fitness by protecting symbiosis against host-inflicted damage during development and by controlling parasite infections in adults that can otherwise reduce host fecundity. PMID:22689989

  15. Maternal transfer of antibodies in vertebrates: trans-generational effects on offspring immunity

    PubMed Central

    Hasselquist, Dennis; Nilsson, Jan-Åke

    2008-01-01

    Maternal effects by which females provide their offspring with non-genetic factors such as hormones, nutrients and antibodies can have an important impact on offspring fitness. In vertebrates, maternal antibodies (matAb) are transferred from the mother, via the placenta, egg yolk or milk during lactation to offspring until they are 2 weeks (birds), 4–10 weeks (rodents) and 9 months (humans) old, respectively. matAb transfer can have direct effects on offspring growth rate in birds and rodents, probably by passively protecting the newborn from common pathogens before their endogenous immune system has matured. Indirect long-term effects of matAb transfer on the offspring's own immunity can be synergistic, if matAb act as antigen templates of the accumulated immunological experience of the mother and educate the newborn's immune system. However, it may also be suppressive if matAb reduce antigen presentation to the newborn resulting in antigen-specific blocking of offspring endogenous immunity. Our aim is to review the mechanisms and direct effects of matAb transfer in vertebrates with an emphasis on birds, outline a framework for research on the long-term effects of matAb on the endogenous immune system of the mature offspring and encourage ecological and evolutionary studies of matAb transfer in non-domesticated animals. PMID:18926976

  16. Maternal Immunization Earlier in Pregnancy Maximizes Antibody Transfer and Expected Infant Seropositivity Against Pertussis

    PubMed Central

    Eberhardt, Christiane S.; Blanchard-Rohner, Geraldine; Lemaître, Barbara; Boukrid, Meriem; Combescure, Christophe; Othenin-Girard, Véronique; Chilin, Antonina; Petre, Jean; de Tejada, Begoña Martinez; Siegrist, Claire-Anne

    2016-01-01

    Background. Maternal immunization against pertussis is currently recommended after the 26th gestational week (GW). Data on the optimal timing of maternal immunization are inconsistent. Methods. We conducted a prospective observational noninferiority study comparing the influence of second-trimester (GW 13–25) vs third-trimester (≥GW 26) tetanus-diphtheria-acellular pertussis (Tdap) immunization in pregnant women who delivered at term. Geometric mean concentrations (GMCs) of cord blood antibodies to recombinant pertussis toxin (PT) and filamentous hemagglutinin (FHA) were assessed by enzyme-linked immunosorbent assay. The primary endpoint were GMCs and expected infant seropositivity rates, defined by birth anti-PT >30 enzyme-linked immunosorbent assay units (EU)/mL to confer seropositivity until 3 months of age. Results. We included 335 women (mean age, 31.0 ± 5.1 years; mean gestational age, 39.3 ± 1.3 GW) previously immunized with Tdap in the second (n = 122) or third (n = 213) trimester. Anti-PT and anti-FHA GMCs were higher following second- vs third-trimester immunization (PT: 57.1 EU/mL [95% confidence interval {CI}, 47.8–68.2] vs 31.1 EU/mL [95% CI, 25.7–37.7], P < .001; FHA: 284.4 EU/mL [95% CI, 241.3–335.2] vs 140.2 EU/mL [95% CI, 115.3–170.3], P < .001). The adjusted GMC ratios after second- vs third-trimester immunization differed significantly (PT: 1.9 [95% CI, 1.4–2.5]; FHA: 2.2 [95% CI, 1.7–3.0], P < .001). Expected infant seropositivity rates reached 80% vs 55% following second- vs third-trimester immunization (adjusted odds ratio, 3.7 [95% CI, 2.1–6.5], P < .001). Conclusions. Early second-trimester maternal Tdap immunization significantly increased neonatal antibodies. Recommending immunization from the second trimester onward would widen the immunization opportunity window and could improve seroprotection. PMID:26797213

  17. HIV-associated chronic immune activation

    PubMed Central

    Paiardini, Mirko; Müller-Trutwin, Michaela

    2013-01-01

    Summary Systemic chronic immune activation is considered today as the driving force of CD4+ T-cell depletion and acquired immunodeficiency syndrome (AIDS). A residual chronic immune activation persists even in HIV-infected patients in which viral replication is successfully inhibited by antiretroviral therapy, with the extent of this residual immune activation being associated with CD4+ T-cell loss. Unfortunately, the causal link between chronic immune activation and CD4+ T-cell loss has not been formally established. This article provides first a brief historical overview on how the perception of the causative role of immune activation has changed over the years and lists the different kinds of immune activation that have been observed to be characteristic for human immunodeficiency virus (HIV) infection. The mechanisms proposed to explain the chronic immune activation are multiple and are enumerated here, as well as the mechanisms proposed on how chronic immune activation could lead to AIDS. In addition, we summarize the lessons learned from natural hosts that know how to ‘show AIDS the door’, and discuss how these studies informed the design of novel immune modulatory interventions that are currently being tested. Finally, we review the current approaches aimed at targeting chronic immune activation and evoke future perspectives. PMID:23772616

  18. Decidual vascular endothelial cells promote maternal-fetal immune tolerance by inducing regulatory T cells through canonical Notch1 signaling.

    PubMed

    Yao, Yanyi; Song, Jieping; Wang, Weipeng; Liu, Nian

    2016-05-01

    Adaptation of the maternal immune response to accommodate the semiallogeneic fetus is necessary for pregnancy success. However, the mechanisms by which the fetus avoids rejection despite expression of paternal alloantigens remain incompletely understood. Regulatory T cells (Treg cells) are pivotal for maintaining immune homeostasis, preventing autoimmune disease and fetus rejection. In this study, we found that maternal decidual vascular endothelial cells (DVECs) sustained Foxp3 expression in resting Treg cells in vitro. Moreover, under in vitro Treg cell induction condition with agonistic antibodies and transforming growth factor (TGF)-β, DVECs promoted Treg cell differentiation from non-Treg conventional T cells. Consistent with the promotion of Treg cell maintenance and differentiation, Treg cell-associated gene expression such as TGF-β, Epstein-Barr-induced gene-3, CD39 and glucocorticoid-induced tumor necrosis factor receptor was also increased in the presence of DVECs. Further study revealed that DVECs expressed Notch ligands such as Jagged-1, Delta-like protein 1 (DLL-1) and DLL-4, while Treg cells expressed Notch1 on their surface. The effects of DVECs on Treg cells was inhibited by siRNA-induced knockdown of expression of Jagged-1 and DLL-1 in DVECs. Downregulation of Notch1 in Treg cells using lentiviral shRNA transduction decreased Foxp3 expression in Treg cells. Adoptive transfer of Notch1-deficient Treg cells increased abortion rate in a murine semiallogeneic pregnancy model. Taken together, our study suggests that maternal DVECs are able to maintain decidual Treg cell identity and promote Treg cell differentiation through activation of Notch1 signal pathway in Treg cells and subsequently inhibit the immune response against semiallogeneic fetuses and preventing spontaneous abortion. PMID:26714886

  19. Dual Positive Regulation of Embryo Implantation by Endocrine and Immune Systems--Step-by-Step Maternal Recognition of the Developing Embryo.

    PubMed

    Fujiwara, Hiroshi; Araki, Yoshihiko; Imakawa, Kazuhiko; Saito, Shigeru; Daikoku, Takiko; Shigeta, Minoru; Kanzaki, Hideharu; Mori, Takahide

    2016-03-01

    In humans, HCG secreted from the implanting embryo stimulates progesterone production of the corpus luteum to maintain embryo implantation. Along with this endocrine system, current evidence suggests that the maternal immune system positively contributes to the embryo implantation. In mice, immune cells that have been sensitized with seminal fluid and then the developing embryo induce endometrial differentiation and promote embryo implantation. After hatching, HCG activates regulatory T and B cells through LH/HCG receptors and then stimulates uterine NK cells and monocytes through sugar chain receptors, to promote and maintain pregnancy. In accordance with the above, the intrauterine administration of HCG-treated PBMC was demonstrated to improve implantation rates in women with repeated implantation failures. These findings suggest that the maternal immune system undergoes functional changes by recognizing the developing embryos in a stepwise manner even from a pre-fertilization stage and facilitates embryo implantation in cooperation with the endocrine system. PMID:26755274

  20. The influence of maternal prenatal and early childhood nutrition and maternal prenatal stress on offspring immune system development and neurodevelopmental disorders

    PubMed Central

    Marques, Andrea Horvath; O'Connor, Thomas G.; Roth, Christine; Susser, Ezra; Bjørke-Monsen, Anne-Lise

    2013-01-01

    The developing immune system and central nervous system in the fetus and child are extremely sensitive to both exogenous and endogenous signals. Early immune system programming, leading to changes that can persist over the life course, has been suggested, and other evidence suggests that immune dysregulation in the early developing brain may play a role in neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. The timing of immune dysregulation with respect to gestational age and neurologic development of the fetus may shape the elicited response. This creates a possible sensitive window of programming or vulnerability. This review will explore the effects of maternal prenatal and infant nutritional status (from conception until early childhood) as well as maternal prenatal stress and anxiety on early programming of immune function, and how this might influence neurodevelopment. We will describe fetal immune system development and maternal-fetal immune interactions to provide a better context for understanding the influence of nutrition and stress on the immune system. Finally, we will discuss the implications for prevention of neurodevelopmental disorders, with a focus on nutrition. Although certain micronutrient supplements have shown to both reduce the risk of neurodevelopmental disorders and enhance fetal immune development, we do not know whether their impact on immune development contributes to the preventive effect on neurodevelopmental disorders. Future studies are needed to elucidate this relationship, which may contribute to a better understanding of preventative mechanisms. Integrating studies of neurodevelopmental disorders and prenatal exposures with the simultaneous evaluation of neural and immune systems will shed light on mechanisms that underlie individual vulnerability or resilience to neurodevelopmental disorders and ultimately contribute to the development of primary preventions and early interventions. PMID:23914151

  1. Maternal uptake of pertussis cocooning strategy and other pregnancy related recommended immunizations.

    PubMed

    Wong, C Y; Thomas, N J; Clarke, M; Boros, C; Tuckerman, J; Marshall, H S

    2015-01-01

    Maternal immunization is an important strategy to prevent severe morbidity and mortality in mothers and their offspring. This study aimed to identify whether new parents were following immunization recommendations prior to pregnancy, during pregnancy, and postnatally. A cross-sectional survey was conducted by a questionnaire administered antenatally to pregnant women attending a maternity hospital with a follow-up telephone interview at 8-10 weeks post-delivery. Factors associated with uptake of pertussis vaccination within the previous 5 y or postnatally and influenza vaccination during pregnancy were explored using log binomial regression models. A total of 297 pregnant women completed the questionnaire. For influenza vaccine, 20.3% were immunized during pregnancy and 3.0% postnatally. For pertussis vaccine, 13.1% were vaccinated within 5 y prior to pregnancy and 31 women received the vaccine postnatally, 16 (51.6%) received the vaccine >4 weeks after delivery. Receiving a recommendation from a healthcare provider (HCP) was an independent predictor for receipt of both pertussis (RR 2.07, p < 0.001) and influenza vaccine (RR 2.26, p = 0.001). Non-English speaking mothers were significantly less likely to have received pertussis vaccination prior to pregnancy or postnatally (RR 0.24, p = 0.011). Multiparous pregnant women were less likely to have received an influenza vaccine during their current pregnancy (p = 0.015). Uptake of pregnancy related immunization is low and likely due to poor knowledge of availability, language barriers and lack of recommendations from HCPs. Strategies to improve maternal vaccine uptake should include education about recommended vaccines for both HCPs and parents and written information in a variety of languages.

  2. Sex-specific effects of maternal immunization on yolk antibody transfer and offspring performance in zebra finches

    PubMed Central

    Martyka, Rafał; Rutkowska, Joanna; Cichoń, Mariusz

    2011-01-01

    Trans-generational antibody transfer constitutes an important mechanism by which mothers may enhance offspring resistance to pathogens. Thus, differential antibody deposition may potentially allow a female to differentiate offspring performance. Here, we examined whether maternal immunization with sheep red blood cells (SRBC) prior to egg laying affects sex-specific yolk antibody transfer and sex-specific offspring performance in zebra finches (Taeniopygia guttata). We showed that immunized mothers deposit anti-SRBC antibodies into the eggs depending on embryo sex and laying order, and that maternal exposure to SRBC positively affects the body size of female, but not male offspring. This is the first study reporting sex-specific consequences of maternal immunization on offspring performance, and suggests that antibody transfer may constitute an adaptive mechanism of maternal favouritism. PMID:20667842

  3. Neural invasion of two virulent suid herpesvirus 1 strains in neonatal pigs with or without maternal immunity.

    PubMed

    Kritas, S K; Pensaert, M B; Nauwynck, H J; Kyriakis, S C

    1999-09-15

    The neural invasion of two virulent Suid Herpesvirus 1 (SHV1) strains was examined in neonatal pigs with or without maternal immunity. One-week-old pigs with comparable levels of maternal immunity (SN-titer = 12-48) were intranasally inoculated with 10(7.0) TCID50 of either of the Ka or E21 strains. The invasion of the strains was examined in the nasal mucosa and in three neuronal levels of the trigeminal nervous pathway as well as in three levels of the olfactory nervous pathway by virus titration and immunohistochemistry (IHC). In control pigs without specific antibodies, both strains invaded up to the end level of each neural pathway. In pigs with maternal immunity, the Ka strain invaded only up to the 2nd level of each pathway with titers being significantly lower (p<0.05) than in the negative controls. However, the E21 strain invaded up to the end levels in both neural pathways of immune pigs with virus titers being similar to those observed in non-immune pigs (p>0.05). IHC revealed that maternal antibodies can protect against a fibroblast-mediated spread of the Ka strain in the lamina propria of the nasal mucosa, as well as against a local spread of the Ka and E21 strains from neurons to their satellite cells in the trigeminal ganglion. In conclusion, the nature of virus strain determines the invasion of SHV1 within the nervous system of maternally-immune neonatal pigs.

  4. Zygotic genome activation during the maternal-to-zygotic transition

    PubMed Central

    Lee, Miler T.; Bonneau, Ashley R.; Giraldez, Antonio J.

    2015-01-01

    Embryogenesis depends on a highly coordinated cascade of genetically encoded events. In animals, maternal factors contributed by the egg cytoplasm initially control development, while the zygotic nuclear genome is quiescent. Subsequently, the genome is activated, embryonic gene products are mobilized and maternal factors are cleared. This transfer of developmental control is called the maternal-to-zygotic transition (MZT). In this review, we discuss recent advances toward understanding the scope, timing and mechanisms that underlie zygotic genome activation at the MZT in animals. We describe high-throughput techniques to measure the embryonic transcriptome and explore how regulation of the cell cycle, chromatin and transcription factors together elicits specific patterns of embryonic gene expression. Finally, we discuss the interplay between zygotic transcription and maternal clearance, and show how these two activities combine to reprogram two terminally differentiated gametes into a totipotent embryo. PMID:25150012

  5. Immune activation generates corticosterone-mediated terminal reproductive investment in a wild bird

    PubMed Central

    Bowers, E. Keith; Bowden, Rachel M.; Sakaluk, Scott K.; Thompson, Charles F.

    2015-01-01

    Despite classical expectations of a trade-off between immune activity and reproduction, an emergent view suggests that individuals experiencing activation of their immune system actually increase reproductive effort and allocation to offspring as a form of terminal investment in response to reduced survival probability. However, the components and mechanisms of increased parental investment following immunostimulation are currently unknown. We hypothesize that increased glucocorticoid production following immunostimulation modulates the increase in reproductive effort that constitutes terminal investment. We activated the immune system of breeding female house wrens (Troglodytes aedon) with an immunogen and cross-fostered the eggs they subsequently produced to separate pre- and post-natal components of maternal investment. Cross-fostering revealed an increase in both pre- and post-natal allocation from immunostimulated females, which was confirmed by quantification of egg constituents and maternal provisioning behavior. The increase in maternal provisioning was mediated, at least in part, by increased corticosterone in these females. Offspring immune responsiveness was also enhanced through transgenerational immune priming via the egg. Thus, our results indicate that maternal immunostimulation induces transgenerational effects on offspring through both pre- and post-natal parental effects, and support an important role for corticosterone in mediating parental investment. PMID:25996862

  6. Sexual orientation, fraternal birth order, and the maternal immune hypothesis: a review.

    PubMed

    Bogaert, Anthony F; Skorska, Malvina

    2011-04-01

    In 1996, psychologists Ray Blanchard and Anthony Bogaert found evidence that gay men have a greater number of older brothers than do heterosexual men. This "fraternal birth order" (FBO) effect has been replicated numerous times, including in non-Western samples. More recently, strong evidence has been found that the FBO effect is of prenatal origin. Although there is no direct support for the exact prenatal mechanism, the most plausible explanation may be immunological in origin, i.e., a mother develops an immune reaction against a substance important in male fetal development during pregnancy, and that this immune effect becomes increasingly likely with each male gestation. This immune effect is hypothesized to cause an alteration in (some) later born males' prenatal brain development. The target of the immune response may be molecules (i.e., Y-linked proteins) on the surface of male fetal brain cells, including in sites of the anterior hypothalamus, which has been linked to sexual orientation in other research. Antibodies might bind to these molecules and thus alter their role in typical sexual differentiation, leading some later born males to be attracted to men as opposed to women. Here we review evidence in favor of this hypothesis, including recent research showing that mothers of boys develop an immune response to one Y-linked protein (i.e., H-Y antigen; SMCY) important in male fetal development, and that this immune effect becomes increasingly likely with each additional boy to which a mother gives birth. We also discuss other Y-linked proteins that may be relevant if this hypothesis is correct. Finally, we discuss issues in testing the maternal immune hypothesis of FBO. PMID:21315103

  7. Translocation of bacteria from the gut to the eggs triggers maternal transgenerational immune priming in Tribolium castaneum

    PubMed Central

    Knorr, Eileen; Schmidtberg, Henrike; Arslan, Derya; Bingsohn, Linda; Vilcinskas, Andreas

    2015-01-01

    Invertebrates can be primed to enhance their protection against pathogens they have encountered before. This enhanced immunity can be passed maternally or paternally to the offspring and is known as transgenerational immune priming. We challenged larvae of the red flour beetle Tribolium castaneum by feeding them on diets supplemented with Escherichia coli, Micrococcus luteus or Pseudomonas entomophila, thus mimicking natural exposure to pathogens. The oral uptake of bacteria induced immunity-related genes in the offspring, but did not affect the methylation status of the egg DNA. However, we observed the translocation of bacteria or bacterial fragments from the gut to the developing eggs via the female reproductive system. Such translocating microbial elicitors are postulated to trigger bacterial strain-specific immune responses in the offspring and provide an alternative mechanistic explanation for maternal transgenerational immune priming in coleopteran insects. PMID:26701756

  8. Heritable variation in maternally derived yolk androgens, thyroid hormones and immune factors.

    PubMed

    Ruuskanen, S; Gienapp, P; Groothuis, T G G; Schaper, S V; Darras, V M; Pereira, C; de Vries, B; Visser, M E

    2016-09-01

    Maternal reproductive investment can critically influence offspring phenotype, and thus these maternal effects are expected to be under strong natural selection. Knowledge on the extent of heritable variation in the physiological mechanisms underlying maternal effects is however limited. In birds, resource allocation to eggs is a key mechanism for mothers to affect their offspring and different components of the egg may or may not be independently adjusted. We studied the heritability of egg components and their genetic and phenotypic covariation in great tits (Parus major), using captive-bred full siblings of wild origin. Egg mass, testosterone (T) and androstenedione (A4) hormone concentrations showed moderate heritability, in agreement with earlier findings. Interestingly, yolk triiodothyronine hormone (T3), but not its precursor, thyroxine hormone (T4), concentration was heritable. An immune factor, albumen lysozyme, showed moderate heritability, but yolk immunoglobulins (IgY) did not. The genetic correlation estimates were moderate but statistically nonsignificant; a trend for a positive genetic correlation was found between A4 and egg mass, T and lysozyme and IgY and lysozyme, respectively. Interestingly, phenotypic correlations were found only between A4 and T, and T4 and T3, respectively. Given that these egg components are associated with fitness-related traits in the offspring (and mother), and that we show that some components are heritable, it opens the possibility that natural selection may shape the rate and direction of phenotypic change via egg composition. PMID:27381323

  9. Association of postpartum maternal tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine administration and timeliness of infant immunization.

    PubMed

    Kaur, Ishminder; George, Krissa J; Pena-Ricardo, Carolina; Kelly, Barbara A; Watson, Barbara

    2013-11-01

    A retrospective cohort study was conducted on infants of mothers delivering at an inner-city hospital in October 2009 where postpartum maternal tetanus toxoid, reduced diptheria toxoid and acellular pertussis (Tdap) vaccination had been initiated in May 2008. We compared mothers and infants in a Tdap intervention group discharged July 2008 (n=250) with a pre-Tdap control group discharged July 2007 (n=238). Postpartum maternal Tdap impacted positively timeliness of early infant immunization.

  10. Prenatal passive transfer of maternal immunity in Asian elephants (Elephas maximus).

    PubMed

    Nofs, Sally A; Atmar, Robert L; Keitel, Wendy A; Hanlon, Cathleen; Stanton, Jeffrey J; Tan, Jie; Flanagan, Joseph P; Howard, Lauren; Ling, Paul D

    2013-06-15

    Asian (Elephas maximus) and African (Loxodonta africana) elephants exhibit characteristics of endotheliochorial placentation, which is common in carnivore species and is associated with modest maternal to fetal transplacental antibody transfer. However, it remains unknown whether the bulk of passive immune transfer in elephants is achieved prenatally or postnatally through ingestion of colostrum, as has been documented for horses, a species whose medical knowledgebase is often extrapolated for elephants. To address this issue, we took advantage of the fact that many zoo elephants are immunized with tetanus toxoid and/or rabies vaccines as part of their routine health care, allowing a comparison of serum antibody levels against these antigens between dams and neonates. Serum samples were collected from 3 newborn Asian elephant calves at birth (before ingestion of colostrum); 2-4 days after birth; and 2-3 months of age. The findings indicate that the newborns had anti-tetanus toxoid and anti-rabies titers that were equivalent to or higher than the titers of their dams from birth to approximately 3 months of age, suggesting that the majority of maternal-to-fetal transfer is transplacental and higher than expected based on the architecture of the Asian elephant placenta.

  11. Antibody response and maternal immunity upon boosting PRRSV-immune sows with experimental farm-specific and commercial PRRSV vaccines.

    PubMed

    Geldhof, Marc F; Van Breedam, Wander; De Jong, Ellen; Lopez Rodriguez, Alfonso; Karniychuk, Uladzimir U; Vanhee, Merijn; Van Doorsselaere, Jan; Maes, Dominiek; Nauwynck, Hans J

    2013-12-27

    attenuated EU-type vaccine in immune sows at 60 days of gestation. The impact of this vaccination on maternal immunity and on the PRRSV infection pattern in piglets during their first weeks of life was evaluated. Upon vaccination with the farm-specific inactivated vaccine, a significant increase in farm-specific virus-neutralizing antibodies was detected in all sows. Virus-neutralizing antibodies were also transferred to the piglets via colostrum and were detectable in the serum of these animals until 5 weeks after parturition. In contrast, not all sows vaccinated with the commercial attenuated vaccine showed an increase in farm-specific virus-neutralizing antibodies and the piglets of this group generally had lower virus-neutralizing antibody titers. Interestingly, the number of viremic animals (i.e. animals that have infectious virus in their bloodstream) was significantly lower among piglets of both vaccinated groups than among piglets of mock-vaccinated sows and this at least until 9 weeks after parturition. The results of this study indicate that inactivated farm-specific PRRSV vaccines and commercial attenuated vaccines can be useful tools to boost PRRSV-specific (humoral) immunity in sows and reduce viremia in weaned piglets.

  12. Maternal prefrontal cortex activation by newborn infant odors.

    PubMed

    Nishitani, Shota; Kuwamoto, Saori; Takahira, Asuka; Miyamura, Tsunetake; Shinohara, Kazuyuki

    2014-03-01

    Mothers are attracted by infant cues of a variety of different modalities. To clarify the possible neural mechanisms underlying maternal attraction to infant odor cues, we used near-infrared spectroscopy to examine prefrontal cortex (PFC) activity during odor detection tasks in which 19 mothers and 19 nulliparous females (nonmothers) were presented with infant or adult male odors. They were instructed to make a judgment about whether they smelled an odor during each task. We estimated the PFC activity by measuring the relative oxyhemoglobin (oxyHb) concentrations. The results showed that while detecting the infant odors, bilateral PFC activities were increased in mothers but not in nonmothers. In contrast, adult male odors activated the PFC similarly in mothers and nonmothers. These findings suggest that maternal activation of the PFC in response to infant odors explains a part of the neural mechanisms for maternal attraction to infant odors.

  13. Maternally acquired IgG immunity in neonates born to renal transplanted women.

    PubMed

    Viana, Patrícia Oliveira; Ono, Erika; Dinelli, Maria Isabel Saraiva; Costa-Carvalho, Beatriz Tavares; Santos, Amélia Miyashiro Nunes Dos; Sass, Nelson; Moraes-Pinto, Maria Isabel de

    2015-06-17

    Neonates born to renal transplanted women are exposed in utero to immunosuppressors and to antenatal conditions that may predispose the neonate to a high risk of prematurity and intrauterine growth retardation. These factors might interfere with the transfer of maternal IgG immunity. Total IgG levels and specific antibodies to measles, varicella, tetanus, Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (serotypes 4,6B,9V,14,18C,19F and 23F) were evaluated on maternal and cord blood samples of 23 sets of renal transplanted women and their newborns and 32 sets of healthy women-newborns at term. Total IgG levels were measured by nephelometry and specific antibodies, by ELISA. Renal transplanted mothers had lower median tetanus antibodies (0.67IU/mL) than controls (1.53IU/mL; p=0.017). Neonates from renal transplanted mothers had lower median tetanus antibodies (0.95IU/mL) than controls (1.97IU/mL, p=0.008). Antibodies to measles, varicella, Hib and the 7 serotypes of S. pneumoniae were similar between groups. Maternal antibodies were associated with an increase in neonatal antibodies for all antigens; gestational age was associated with an increase in Hib neonatal antibodies. Preeclampsia was associated with a decrease in neonatal total IgG and serotype 4 S. pneumoniae antibodies; chronic hypertension was associated with a decrease in neonatal serotype 6B S. pneumoniae antibodies. As neonates from transplanted women may be born with lower tetanus antibodies than controls, efforts should be made to keep maternal vaccines up-to-date. Clinical antenatal care with control of preeclampsia, chronic hypertension and prevention of premature delivery might also contribute to neonatal antibody levels to specific antigens at birth. PMID:25987539

  14. Maternal determinants of complete child immunization among children aged 12-23 months in a southern district of Nigeria.

    PubMed

    Fatiregun, Akinola Ayoola; Okoro, Anselm O

    2012-01-17

    This study was conducted to identify determinants of complete immunization status among children aged 12-23 months in a southern district of Nigeria. The World Health Organization cluster survey was used to evaluate immunization coverage of infants. Mothers of 525 children selected by the two-stage sampling method and interviewed using an adapted questionnaire responded. Completion of the immunization schedule was verified by an immunization card or by reported history indicating that the child had received full doses of four of the antigens included in the Nigeria routine immunization schedule. Multivariate logistic regression was used to identify factors associated with completion of immunization. Only 32.4% of children had completed the immunization schedule. Determinants of complete immunization status included a maternal age less than 30 years (AOR=2.26, 95% CI:1.27-4.03), availability of an immunization card at first contact (AOR=7.72, 95% CI:4.43-13.44), fewer than three children (AOR=2.22, 95% CI:11.1-4.42), completion of post secondary education (AOR=2.34, 95% CI:1.12-4.47) and maternal unemployment (AOR=1.71, 95% CI:1.01-2.89). Identifying mothers whose children are at risk of not completing the immunization schedule and educating them is an important strategy to improve antigen coverage and prevent early childhood deaths from diseases like tuberculosis, poliomyelitis, tetanus, diphtheria, pertussis and measles. PMID:22137878

  15. Asthma-Related Immune Responses in Youth With Asthma: Associations With Maternal Responsiveness and Expressions of Positive and Negative Affect in Daily Life

    PubMed Central

    Tobin, Erin T.; Kane, Heidi S.; Saleh, Daniel J.; Wildman, Derek E.; Breen, Elizabeth Crabb; Secord, Elizabeth; Slatcher, Richard B.

    2015-01-01

    Objective Stressful family environments early in life have negative effects on physical health. However, less is known about the health effects of positive aspects of families. We examined the associations between maternal responsiveness and immune markers among youth with asthma and identified youth expressions of positive affect as a potential mechanism of these associations. Methods Forty-three youths with asthma (26 males; aged 10-17) wore the Electronically Activated Recorder (EAR) for four days to assess maternal responsiveness and youth expressions of affect from audio-recordings of daily life. Trained coders rated EAR sound files for expressions of maternal responsiveness and affect displayed by the youth. Peripheral blood mononuclear cells were isolated, cultured, and assayed to determine stimulated levels of interleukin(IL)-5, IL-13, and interferon(IFN)- γ. Results Greater maternal responsiveness was associated with decreased stimulated production of IL-5 (r = −.38, p = .012) and IL-13 (r = −.33, p = .031). Greater total positive affect in youth was linked with decreased stimulated production of IL-5 (r = −.46, p = .002) and IL-13 (r = −.37, p = .014). Total negative affect among youth was unrelated to immune responses. There was a significant indirect effect of maternal responsiveness via positive affect in youth on lower levels of IL-5 (95% CI = −3.41, −.03) and IL-13 (95% CI = −2.34, −.01) when adjusting for caregiver-youth conflict and negative affect among youth. Conclusions These results indicate the importance of positive family interactions for youth and provide preliminary evidence for a mechanism through which parenting can influence immune responses in youths with asthma. PMID:26407226

  16. Maternal celiac disease autoantibodies bind directly to syncytiotrophoblast and inhibit placental tissue transglutaminase activity

    PubMed Central

    Anjum, Naheed; Baker, Philip N; Robinson, Nicola J; Aplin, John D

    2009-01-01

    Background Celiac disease (CD) occurs in as many as 1 in 80 pregnant women and is associated with poor pregnancy outcome, but it is not known if this is an effect on maternal nutrient absorption or, alternatively, if the placenta is an autoimmune target. The major autoantigen, tissue transglutaminase (tTG), has previously been shown to be present in the maternal-facing syncytiotrophoblast plasma membrane of the placenta. Methods ELISA was used to demonstrate the presence of antibodies to tissue transglutaminase in a panel of CD sera. Immunohistochemistry was used to evaluate the binding of IgA autoantibodies from CD serum to term placenta. In addition, novel direct binding and activity assays were developed to mimic the in vivo exposure of the villous placenta to maternal autoantibody. Results and Discussion CD IgA autoantibodies located to the syncytial surface of the placenta significantly more than IgA antibodies in control sera (P < 0.0001). The distribution of antigen was similar to that observed using a monoclonal antibody to tissue transglutaminase. Staining was reduced by pre-absorption of CD serum with recombinant human tissue transglutaminase. In direct binding assays, autoimmune immunoglobulin A (IgA) from the maternal compartment became associated with antigen at the syncytial surface of the placenta, as a result of which transglutaminase activity at this site was inhibited. Conclusion These data indicate that direct immune effects in untreated CD women may compromise placental function. PMID:19228395

  17. Effect of maternal exposure to ozone on reproductive outcome and immune, inflammatory, and allergic responses in the offspring

    EPA Science Inventory

    There is growing concern that exposure to air pollutants during pregnancy affects health outcomes in the offspring due to alterations in the development of immune and other homeostatic processes. To assess the risks of maternal inhalation exposure to ozone (O3), timed pregnant BA...

  18. Immune response in mice to ingested soya protein: antibody production, oral tolerance and maternal transfer.

    PubMed

    Christensen, Hanne R; Brix, Susanne; Frøkiaer, Hanne

    2004-05-01

    While allergic reactions to soya are increasingly investigated, the normal immune response to ingested soya is scarcely described. In the present study, we wanted to characterise the soya-specific immune response in healthy mice ingesting soya protein. Mice fed a soya-containing diet (F0) and mice of the first (F1) and second (F2) offspring generation bred on a soya protein-free diet were used either directly or were transferred between the soya-containing and soya protein-free diet during pregnancy or neonatal life. The mice were compared as to levels of naturally occurring specific antibodies analysed by ELISA, and to the presence of oral tolerance detected as a suppressed antibody and cell-proliferation response upon immunisation with soya protein. F0 mice generated soya-specific antibodies, while oral tolerance to the same soya proteins was also clearly induced. When F0 dams were transferred to soya protein-free feed before mating, the F1 and F2 offspring generations showed no significantly different response, indicating that soya-specific immune components were not maternally transmitted. However, the ingestion of dietary soya protein by F1 mice during late pregnancy and lactation caused a lasting antibody response in the offspring, but in this case in the absence of oral tolerance. This indicates that, under certain conditions, factors involved in spontaneous antibody production can be transmitted from mother to offspring. Understanding the immune response to soya protein ingested under healthy conditions is important in the assessment of adverse effects of soya protein and in the use of animal allergy models. The present results add to this understanding. PMID:15137924

  19. Advancing the detection of maternal haematopoietic microchimeric cells in fetal immune organs in mice by flow cytometry

    PubMed Central

    Solano, Maria Emilia; Thiele, Kristin; Stelzer, Ina Annelies; Mittrücker, Hans-Willi; Arck, Petra Clara

    2014-01-01

    Maternal microchimerism, which occurs naturally during gestation in hemochorial placental mammals upon transplacental migration of maternal cells into the fetus, is suggested to significantly influence the fetal immune system. In our previous publication, we explored the sensitivity of quantitative polymerase chain reaction and flow cytometry to detect cellular microchimerism. With that purpose, we created mixed cells suspensions in vitro containing reciprocal frequencies of wild type cells and cells positive for enhanced green fluorescent protein or CD45.1+, respectively. Here, we now introduce the H-2 complex, which defines the major histocompatibility complex in mice and is homologous to HLA in human, as an additional target to detect maternal microchimerism among fetal haploidentical cells. We envision that this advanced approach to detect maternal microchimeric cells by flow cytometry facilitates the pursuit of phenotypic, gene expression and functional analysis of microchimeric cells in future studies. PMID:25483743

  20. Protection of Mice against Shiga Toxin 2 (Stx2)-Associated Damage by Maternal Immunization with a Brucella Lumazine Synthase-Stx2 B Subunit Chimera

    PubMed Central

    Mejias, María Pilar; Cabrera, Gabriel; Fernández-Brando, Romina Jimena; Baschkier, Ariela; Ghersi, Giselle; Abrey-Recalde, Maria Jimena; Miliwebsky, Elizabeth; Meiss, Roberto; Goldbaum, Fernando; Zylberman, Vanesa; Rivas, Marta

    2014-01-01

    Hemolytic-uremic syndrome (HUS) is defined as the triad of anemia, thrombocytopenia, and acute kidney injury. Enterohemorrhagic Shiga toxin (Stx)-producing Escherichia coli (EHEC), which causes a prodromal hemorrhagic enteritis, remains the most common etiology of the typical or epidemic form of HUS. Because no licensed vaccine or effective therapy is presently available for human use, we recently developed a novel immunogen based on the B subunit of Shiga toxin 2 (Stx2B) and the enzyme lumazine synthase from Brucella spp. (BLS) (BLS-Stx2B). The aim of this study was to analyze maternal immunization with BLS-Stx2B as a possible approach for transferring anti-Stx2 protection to the offspring. BALB/c female mice were immunized with BLS-Stx2B before mating. Both dams and pups presented comparable titers of anti-Stx2B antibodies in sera and fecal extracts. Moreover, pups were totally protected against a lethal dose of systemic Stx2 injection up to 2 to 3 months postpartum. In addition, pups were resistant to an oral challenge with an Stx2-producing EHEC strain at weaning and did not develop any symptomatology associated with Stx2 toxicity. Fostering experiments demonstrated that anti-Stx2B neutralizing IgG antibodies were transmitted through breast-feeding. Pups that survived the EHEC infection due to maternally transferred immunity prolonged an active and specific immune response that protected them against a subsequent challenge with intravenous Stx2. Our study shows that maternal immunization with BLS-Stx2B was very effective at promoting the transfer of specific antibodies, and suggests that preexposure of adult females to this immunogen could protect their offspring during the early phase of life. PMID:24421050

  1. Maternal activation of gap genes in the hover fly Episyrphus.

    PubMed

    Lemke, Steffen; Busch, Stephanie E; Antonopoulos, Dionysios A; Meyer, Folker; Domanus, Marc H; Schmidt-Ott, Urs

    2010-05-01

    The metameric organization of the insect body plan is initiated with the activation of gap genes, a set of transcription-factor-encoding genes that are zygotically expressed in broad and partially overlapping domains along the anteroposterior (AP) axis of the early embryo. The spatial pattern of gap gene expression domains along the AP axis is generally conserved, but the maternal genes that regulate their expression are not. Building on the comprehensive knowledge of maternal gap gene activation in Drosophila, we used loss- and gain-of-function experiments in the hover fly Episyrphus balteatus (Syrphidae) to address the question of how the maternal regulation of gap genes evolved. We find that, in Episyrphus, a highly diverged bicoid ortholog is solely responsible for the AP polarity of the embryo. Episyrphus bicoid represses anterior zygotic expression of caudal and activates the anterior and central gap genes orthodenticle, hunchback and Krüppel. In bicoid-deficient Episyrphus embryos, nanos is insufficient to generate morphological asymmetry along the AP axis. Furthermore, we find that torso transiently regulates anterior repression of caudal and is required for the activation of orthodenticle, whereas all posterior gap gene domains of knirps, giant, hunchback, tailless and huckebein depend on caudal. We conclude that all maternal coordinate genes have altered their specific functions during the radiation of higher flies (Cyclorrhapha).

  2. Association of Maternal Immunity with Rotavirus Vaccine Immunogenicity in Zambian Infants

    PubMed Central

    Chilengi, Roma; Simuyandi, Michelo; Beach, Lauren; Mwila, Katayi; Becker-Dreps, Sylvia; Emperador, Devy M.; Velasquez, Daniel E.; Bosomprah, Samuel; Jiang, Baoming

    2016-01-01

    Introduction Live attenuated oral vaccines against rotavirus (RV) have been shown to be less efficacious in children from developing countries. Reasons for this disparity are not fully understood. We assessed the role of maternal factors including breast milk RV-specific IgA, transplacentally acquired infant serum RV-specific IgG and maternal HIV status in seroconversion among Zambian infants routinely immunized with Rotarix™ (RV1). Methods 420 mother-child pairs were recruited at infant age 6–12 weeks in Lusaka. Clinical information and samples were collected at baseline and at one month following the second dose of RV1. Determination of breast milk RV-specific IgA and serum RV-specific IgA and IgG was done using standardized ELISA. Seroconversion was defined as a ≥ 4 fold rise in serum IgA titre from baseline to one-month post RV1 dose 2, while seropositivity of IgA was defined as serum titre ≥ 40 and antibody variables were modelled on log-base 2. Logistic regression was used to identify predictors of the odds of seroconversion. Results Baseline infant seropositivity was 25.5% (91/357). The seroconversion frequency was 60.2% (130/216). Infants who were IgA seropositive at baseline were less likely to seroconvert compared to their seronegative counterparts (P = 0.04). There was no evidence of an association between maternal HIV status and seroconversion (P = 0.25). Higher titres of breast milk rotavirus-specific IgA were associated with a lower frequency of seroconverson (Nonparametric test for trend Z = -2.84; P<0.01): a two-fold increase in breast milk RV-specific IgA titres was associated with a 22% lower odds of seroconversion (OR = 0.80; 95% CI = 0.68–0.94; P = 0.01). There was seasonal variation in baseline breast milk rotavirus-specific IgA titres, with significantly higher GMTs during the cold dry months (P = 0.01). Conclusion Low immunogenicity of RV1 vaccine could be explained in part by exposure to high antibody titres in breast milk and

  3. Measurement of myeloid cell immune suppressive activity.

    PubMed

    Dolcetti, Luigi; Peranzoni, Elisa; Bronte, Vincenzo

    2010-11-01

    This unit presents simple methods to assess the immunosuppressive properties of immunoregulatory cells of myeloid origin, such as myeloid-derived suppressor cells (MDSCs), both in vitro and in vivo. These methods are general and could be adapted to test the impact of different suppressive populations on T cell activation, proliferation, and cytotoxic activity; moreover they could be useful to assess the influence exerted on immune suppressive pathways by genetic modifications, chemical inhibitors, and drugs.

  4. Bacterial RNAs activate innate immunity in Arabidopsis.

    PubMed

    Lee, Boyoung; Park, Yong-Soon; Lee, Soohyun; Song, Geun Cheol; Ryu, Choong-Min

    2016-01-01

    The common molecular patterns of microbes play a critical role in the regulation of plant innate immunity. However, little is known about the role of nucleic acids in this process in plants. We pre-infiltrated Arabidopsis leaves with total RNAs from Pseudomonas syringae pv. tomato DC3000 (Pto DC3000) and subsequently inoculated these plants with the same bacterial cells. Total Pto DC3000 RNAs pre-infiltrated into Arabidopsis leaves elicited plant immune responses against Pto DC3000. However, sheared RNAs and RNase A application failed to induce immunity, suggesting that intact bacterial RNAs function in plant innate immunity. This notion was supported by the positive regulation of superoxide anion levels, callose deposition, two mitogen-activated protein kinases and defense-related genes observed in bacterial RNA-pre-treated leaves. Intriguingly, the Pto DC3000 population was not compromised in known pattern recognition receptor mutants for chitin, flagellin and elongation factor-Tu (EF-Tu). Plant defense-related mutant analyses further revealed that bacterial RNA-elicited innate immunity was normally required for salicylic and jasmonic acid signaling. Notably, among total RNAs, the abundant bacterial RNA species 16S and 23S ribosomal RNAs were the major determinants of this response. Our findings provide evidence that bacterial RNA serves as a microbe-associated molecular pattern in plants. PMID:26499893

  5. Activation of maternal centrosomes in unfertilized sea urchin eggs

    NASA Technical Reports Server (NTRS)

    Schatten, H.; Walter, M.; Biessmann, H.; Schatten, G.

    1992-01-01

    Centrosomes are undetectable in unfertilized sea urchin eggs, and normally the sperm introduces the cell's microtubule-organizing center (MTOC) at fertilization. However, artificial activation or parthenogenesis triggers microtubule assembly in the unfertilized egg, and this study explores the reappearance and behavior of the maternal centrosome. During activation with A23187 or ammonia, microtubules appear first at the cortex; centrosomal antigen is detected diffusely throughout the entire cytoplasm. Later, the centrosome becomes more distinct and organizes a radial microtubule shell, and eventually a compact centrosome at the egg center organizes a monaster. In these activated eggs, centrosomes undergo cycles of compaction and decompaction in synchrony with the chromatin, which also undergoes cycles of condensation and decondensation. Parthenogenetic activation with heavy water (50% D2O) or the microtubule-stabilizing drug taxol (10 microM) induces numerous centrosomal foci in the unfertilized sea urchin egg. Within 15 min after incubation in D2O, numerous fine centrosomal foci are detected, and they organize a connected network of numerous asters which fill the entire egg. Taxol induces over 100 centrosomal foci by 15 min after treatment, which organize a corresponding number of asters. The centrosomal material in either D2O- or taxol-treated eggs aggregates with time to form fewer but denser foci, resulting in fewer and larger asters. Fertilization of eggs pretreated with either D2O or taxol shows that the paternal centrosome is dominant over the maternal centrosome. The centrosomal material gradually becomes associated with the enlarged sperm aster. These experiments demonstrate that maternal centrosomal material is present in the unfertilized egg, likely as dispersed undetectable material, which can be activated without paternal contributions. At fertilization, paternal centrosomes become dominant over the maternal centrosomal material.

  6. The HLA-G cycle provides for both NK tolerance and immunity at the maternal-fetal interface.

    PubMed

    Tilburgs, Tamara; Evans, J Henry; Crespo, Ângela C; Strominger, Jack L

    2015-10-27

    The interaction of noncytotoxic decidual natural killer cells (dNK) and extravillous trophoblasts (EVT) at the maternal-fetal interface was studied. Confocal microscopy revealed that many dNK interact with a single large EVT. Filamentous projections from EVT enriched in HLA-G were shown to contact dNK, and may represent the initial stage of synapse formation. As isolated, 2.5% of dNK contained surface HLA-G. However, surface HLA-G-negative dNK contained internalized HLA-G. Activation of dNK resulted in the disappearance of internalized HLA-G in parallel with restoration of cytotoxicity. Surface HLA-G was reacquired by incubation with EVT. This HLA-G cycle of trogocytosis, endocytosis, degradation, and finally reacquisition provides a transient and localized acquisition of new functional properties by dNK upon interaction with EVT. Interruption of the cycle by activation of dNK by cytokines and/or viral products serves to ensure the NK control of virus infection at the interface, and is illustrated here by the response of dNK to human cytomegalo virus (HCMV)-infected decidual stromal cells. Thus, the HLA-G cycle in dNK can provide both for NK tolerance and antiviral immunity. PMID:26460007

  7. Developing supplemental activities for primary health care maternity services.

    PubMed

    Panitz, E

    1990-12-01

    Supplemental health care activities are described in the context of the augmented product. The potential benefits of supplemental services to recipients and provider are discussed. The author describes a study that was the basis for (re)developing a supplemental maternity service. The implementation of the results in terms of changes in the marketing mix of this supplemental program is discussed. The effects of the marketing mix changes on program participation are presented.

  8. Innate Immune System at the Maternal-Fetal Interface: Mechanisms of Disease and Targets of Therapy in Pregnancy Syndromes.

    PubMed

    Triggianese, Paola; Perricone, Carlo; Chimenti, Maria Sole; De Carolis, Caterina; Perricone, Roberto

    2016-10-01

    The maternal-fetal interface is an immunologically unique site that allows the tolerance to the allogenic fetus and maintains host defense against possible pathogens. Balanced immune responses are required for the maintenance of successful pregnancy. It has been demonstrated that innate immune disturbances may be responsible for some adverse pregnancy outcomes such as preeclampsia (PE); hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome; intrauterine growth restriction (IUGR); and recurrent spontaneous abortion (RSA). Observational studies suggest that immunomodulatory treatments in pregnancy-specific complications may improve both the hematological/biochemical features in the mother and the perinatal outcomes. The following review will discuss how recent and relevant findings in the field of the innate immunity have advanced our understanding of the role of inflammation and innate immune system in the pathogenesis of pregnancy failure and will discuss the therapeutic outcomes of the existing studies and clinical trials in light of these new insights. PMID:27108670

  9. Human Decidual Stromal Cells as a Component of the Implantation Niche and a Modulator of Maternal Immunity.

    PubMed

    Vinketova, Kameliya; Mourdjeva, Milena; Oreshkova, Tsvetelina

    2016-01-01

    The human decidua is a specialized tissue characterized by embryo-receptive properties. It is formed during the secretory phase of menstrual cycle from uterine mucosa termed endometrium. The decidua is composed of glands, immune cells, blood and lymph vessels, and decidual stromal cells (DSCs). In the process of decidualization, which is controlled by oestrogen and progesterone, DSCs acquire specific functions related to recognition, selection, and acceptance of the allogeneic embryo, as well as to development of maternal immune tolerance. In this review we discuss the relationship between the decidualization of DSCs and pathological obstetrical and gynaecological conditions. Moreover, the critical influence of DSCs on local immune cells populations as well as their relationship to the onset and maintenance of immune tolerance is described. PMID:27239344

  10. Human Decidual Stromal Cells as a Component of the Implantation Niche and a Modulator of Maternal Immunity

    PubMed Central

    Vinketova, Kameliya; Mourdjeva, Milena

    2016-01-01

    The human decidua is a specialized tissue characterized by embryo-receptive properties. It is formed during the secretory phase of menstrual cycle from uterine mucosa termed endometrium. The decidua is composed of glands, immune cells, blood and lymph vessels, and decidual stromal cells (DSCs). In the process of decidualization, which is controlled by oestrogen and progesterone, DSCs acquire specific functions related to recognition, selection, and acceptance of the allogeneic embryo, as well as to development of maternal immune tolerance. In this review we discuss the relationship between the decidualization of DSCs and pathological obstetrical and gynaecological conditions. Moreover, the critical influence of DSCs on local immune cells populations as well as their relationship to the onset and maintenance of immune tolerance is described. PMID:27239344

  11. Effects of inadequate maternal dietary protein:carbohydrate ratios during pregnancy on offspring immunity in pigs

    PubMed Central

    2012-01-01

    Background Inadequate nutrition in utero may retard foetal growth and alter physiological development of offspring. This study investigated the effects of low and high protein diets fed to primiparous German Landrace sows throughout pregnancy on the immune function of their offspring at different ages. Sows were fed diets with adequate (AP, 12.1%; n = 13), low (LP, 6.5%; n = 15), or high (HP, 30%; n = 14) protein content, made isoenergetic by varying carbohydrate levels. Cortisol, total protein and immunoglobulin (IgG, IgM, IgA) concentrations were measured in the blood of sows over the course of pregnancy. Cortisol, total protein, immunoglobulins, lymphocyte proliferation, immune cell counts, and cytokines were assessed in the blood of offspring at baseline and under challenging conditions (weaning; lipopolysaccharide (LPS) administration). Results In sows, the LP diet increased cortisol (P < 0.05) and decreased protein levels (P < 0.01) at the end of pregnancy. Immunoglobulin concentrations were decreased in LP (IgA) and HP piglets (IgG, IgM and IgA) on the first day of life (P < 0.05), whereas the number of lymphocytes and mitogen-induced lymphocyte proliferation of the piglets were unaffected by the maternal diet. Mortality during the suckling period was higher in LP piglets compared with AP and HP offspring (P < 0.01). Furthermore, LP piglets showed an elevated cortisol response to weaning, and in HP piglets, the CD4+ cell percentage and the CD4+/CD8+ ratio increased after weaning (P < 0.05). The lipopolysaccharide-induced rise of IL-6 was higher in LP (P = 0.09) and HP (P < 0.01) compared with AP piglets, and LP piglets displayed higher IL-10 levels than AP piglets (P < 0.05). Conclusions Our results indicate that both low and high protein:carbohydrate ratios in the diet of pregnant sows can induce short-term as well as long-lasting effects on immune competence in piglets that may have serious consequences for host

  12. Therapeutic Targets for Neurodevelopmental Disorders Emerging from Animal Models with Perinatal Immune Activation

    PubMed Central

    Ibi, Daisuke; Yamada, Kiyofumi

    2015-01-01

    Increasing epidemiological evidence indicates that perinatal infection with various viral pathogens enhances the risk for several psychiatric disorders. The pathophysiological significance of astrocyte interactions with neurons and/or gut microbiomes has been reported in neurodevelopmental disorders triggered by pre- and postnatal immune insults. Recent studies with the maternal immune activation or neonatal polyriboinosinic polyribocytidylic acid models of neurodevelopmental disorders have identified various candidate molecules that could be responsible for brain dysfunction. Here, we review the functions of several candidate molecules in neurodevelopment and brain function and discuss their potential as therapeutic targets for psychiatric disorders. PMID:26633355

  13. Estimation of immunization providers' activities cost, medication cost, and immunization dose errors cost in Iraq.

    PubMed

    Al-lela, Omer Qutaiba B; Bahari, Mohd Baidi; Al-abbassi, Mustafa G; Salih, Muhannad R M; Basher, Amena Y

    2012-06-01

    The immunization status of children is improved by interventions that increase community demand for compulsory and non-compulsory vaccines, one of the most important interventions related to immunization providers. The aim of this study is to evaluate the activities of immunization providers in terms of activities time and cost, to calculate the immunization doses cost, and to determine the immunization dose errors cost. Time-motion and cost analysis study design was used. Five public health clinics in Mosul-Iraq participated in the study. Fifty (50) vaccine doses were required to estimate activities time and cost. Micro-costing method was used; time and cost data were collected for each immunization-related activity performed by the clinic staff. A stopwatch was used to measure the duration of activity interactions between the parents and clinic staff. The immunization service cost was calculated by multiplying the average salary/min by activity time per minute. 528 immunization cards of Iraqi children were scanned to determine the number and the cost of immunization doses errors (extraimmunization doses and invalid doses). The average time for child registration was 6.7 min per each immunization dose, and the physician spent more than 10 min per dose. Nurses needed more than 5 min to complete child vaccination. The total cost of immunization activities was 1.67 US$ per each immunization dose. Measles vaccine (fifth dose) has a lower price (0.42 US$) than all other immunization doses. The cost of a total of 288 invalid doses was 744.55 US$ and the cost of a total of 195 extra immunization doses was 503.85 US$. The time spent on physicians' activities was longer than that spent on registrars' and nurses' activities. Physician total cost was higher than registrar cost and nurse cost. The total immunization cost will increase by about 13.3% owing to dose errors.

  14. Using a maternal immune stimulation model of schizophrenia to study behavioral and neurobiological alterations over the developmental course.

    PubMed

    Hadar, Ravit; Soto-Montenegro, M Luisa; Götz, Thomas; Wieske, Franziska; Sohr, Reinhard; Desco, Manuel; Hamani, Clement; Weiner, Ina; Pascau, Javier; Winter, Christine

    2015-08-01

    A growing body of evidence sheds light on the neurodevelopmental nature of schizophrenia with symptoms typically emerging during late adolescence or young adulthood. We compared the pre-symptomatic adolescence period with the full symptomatic period of adulthood at the behavioral and neurobiological level in the poly I:C maternal immune stimulation (MIS) rat model of schizophrenia. We found that in MIS-rats impaired sensorimotor gating, as reflected in disrupted prepusle inhibition (PPI), emerged post-pubertally, with behavioral deficits being only recorded in adulthood but not during adolescence. Using post mortem HPLC we found that MIS-rats show distinct dopamine and serotonin changes in the medial prefrontal cortex (mPFC), nucleus accumbens (Nacc), caudate putamen, globus pallidus, and hippocampus. Further, FDG-PET has shown that these animals had lower glucose uptake in the ventral hippocampus and PFC and a higher metabolism in the amygdala and Nacc when compared to controls. Changes in neurotransmission and metabolic activity varied across brain structures with respect to first appearance and further development. In the mPFC and Hipp, MIS-rats showed abnormal neurochemical and metabolic activity prior to and with the development of behavioral deficits in both adolescent and adult states, reflecting an early impairment of these regions. In contrast, biochemical alteration in the Nacc and globus pallidus developed as a matter of age. Our findings suggest that MIS-induced neurochemical and metabolic changes are neurodevelopmental in nature and either progressive or non-progressive and that the behavioral deficits manifest as these abnormalities increase.

  15. Effect of maternal activity during gestation on maternal behavior, fetal growth, umbilical blood flow, and farrowing characteristics in pigs.

    PubMed

    Harris, E K; Berg, E P; Berg, E L; Vonnahme, K A

    2013-02-01

    Yorkshire gilts either remained in their individual stall from d 40 to term (CON; n = 7) or were subjected to exercise for 30 min 3 times per week from mid to late gestation (EX; n = 7) to determine the impact of increased maternal activity during gestation on maternal behavior, fetal growth, umbilical blood flow, and parturition. In parity 1, maternal body composition (10th rib back fat and LM area), maternal behavior, and farrowing characteristics were recorded. In parities 1 and 2, fetal growth, fetal heart rate, pulsatility index and resistance index, and umbilical blood flow were monitored beginning at d 39 of gestation continuing to d 81 of gestation. Exercise continued until d 104. Gilts allowed to exercise sat less (P < 0.01), stood more (P < 0.01), tended (P = 0.06) to lie down less, and had fewer postural changes (P < 0.01) compared with CON gilts. Umbilical blood flow increased (P < 0.01) in EX compared with CON gilts. Moreover, gilts had greater (P < 0.01) umbilical blood flow in their first parity compared with their second. Indices of vascular resistance were not affected (P ≥ 0.15) by maternal treatment; however, EX gilts reached peak pulsatility index earlier than CON gilts (56.2 vs. 64.3 ± 3.6 d). Fetal weights, piglet birth weights, placental weight, interval between piglet births, and blood lactate of newborn piglets were unaffected (P ≥ 0.15) by maternal treatment. Although maternal exercise during gestation in the pig increased umbilical blood flow and appeared to reduce maternal restlessness, impacts on offspring development in postnatal life are not known. PMID:23148241

  16. Effect of maternal activity during gestation on maternal behavior, fetal growth, umbilical blood flow, and farrowing characteristics in pigs.

    PubMed

    Harris, E K; Berg, E P; Berg, E L; Vonnahme, K A

    2013-02-01

    Yorkshire gilts either remained in their individual stall from d 40 to term (CON; n = 7) or were subjected to exercise for 30 min 3 times per week from mid to late gestation (EX; n = 7) to determine the impact of increased maternal activity during gestation on maternal behavior, fetal growth, umbilical blood flow, and parturition. In parity 1, maternal body composition (10th rib back fat and LM area), maternal behavior, and farrowing characteristics were recorded. In parities 1 and 2, fetal growth, fetal heart rate, pulsatility index and resistance index, and umbilical blood flow were monitored beginning at d 39 of gestation continuing to d 81 of gestation. Exercise continued until d 104. Gilts allowed to exercise sat less (P < 0.01), stood more (P < 0.01), tended (P = 0.06) to lie down less, and had fewer postural changes (P < 0.01) compared with CON gilts. Umbilical blood flow increased (P < 0.01) in EX compared with CON gilts. Moreover, gilts had greater (P < 0.01) umbilical blood flow in their first parity compared with their second. Indices of vascular resistance were not affected (P ≥ 0.15) by maternal treatment; however, EX gilts reached peak pulsatility index earlier than CON gilts (56.2 vs. 64.3 ± 3.6 d). Fetal weights, piglet birth weights, placental weight, interval between piglet births, and blood lactate of newborn piglets were unaffected (P ≥ 0.15) by maternal treatment. Although maternal exercise during gestation in the pig increased umbilical blood flow and appeared to reduce maternal restlessness, impacts on offspring development in postnatal life are not known.

  17. Maternal age effects on myometrial expression of contractile proteins, uterine gene expression, and contractile activity during labor in the rat

    PubMed Central

    Elmes, Matthew; Szyszka, Alexandra; Pauliat, Caroline; Clifford, Bethan; Daniel, Zoe; Cheng, Zhangrui; Wathes, Claire; McMullen, Sarah

    2015-01-01

    Advanced maternal age of first time pregnant mothers is associated with prolonged and dysfunctional labor and significant risk of emergency cesarean section. We investigated the influence of maternal age on myometrial contractility, expression of contractile associated proteins (CAPs), and global gene expression in the parturient uterus. Female Wistar rats either 8 (YOUNG n = 10) or 24 (OLDER n = 10) weeks old were fed laboratory chow, mated, and killed during parturition. Myometrial strips were dissected to determine contractile activity, cholesterol (CHOL) and triglycerides (TAG) content, protein expression of connexin-43 (GJA1), prostaglandin-endoperoxide synthase 2 (PTGS2), and caveolin 1 (CAV-1). Maternal plasma concentrations of prostaglandins PGE2, PGF2α, and progesterone were determined by RIA. Global gene expression in uterine samples was compared using Affymetrix Genechip Gene 2.0 ST arrays and Ingenuity Pathway analysis (IPA). Spontaneous contractility in myometrium exhibited by YOUNG rats was threefold greater than OLDER animals (P < 0.027) but maternal age had no significant effect on myometrial CAP expression, lipid profiles, or pregnancy-related hormones. OLDER myometrium increased contractile activity in response to PGF2α, phenylephrine, and carbachol, a response absent in YOUNG rats (all P < 0.002). Microarray analysis identified that maternal age affected expression of genes related to immune and inflammatory responses, lipid transport and metabolism, steroid metabolism, tissue remodeling, and smooth muscle contraction. In conclusion YOUNG laboring rat myometrium seems primed to contract maximally, whereas activity is blunted in OLDER animals and requires stimulation to meet contractile potential. Further work investigating maternal age effects on myometrial function is required with focus on lipid metabolism and inflammatory pathways. PMID:25876907

  18. The impact of maternal measles-rubella immunization on the 12-month-old infant's immune response to measles-mumps-rubella vaccine immunogenicity.

    PubMed

    Saffar, M-J; Ajami, A; Khalilian, A-R; Saffar, H

    2009-07-01

    This study was conducted to assess the roles of maternal measles-rubella (MR) vaccination before pregnancy on the persistence of passive immunity against MR in their infant before measles-mumps-rubella (MMR) immunization and the effects on the immunogenicity of MMR vaccine. Before and 4-8 weeks after MMR immunization of all healthy 12-month-old infants, sera samples were prepared. According to their mother's history of MR vaccination, infants were divided into two groups. Anti-MR antibodies were measured by the quantitative enzyme-linked immunosorbent assay (ELISA) method. The difference in seroconversion rates and the mean concentration of antibodies (MCA) between the two groups of infants were analyzed by descriptive statistical methods. In total, 7 and 12 sera, all from infants born from MR-vaccinated mothers, were positive against measles and rubella, respectively. The seroconversion rates were 90.5 and 53% in seronegative infants against measles and rubella, respectively, without statistically significant differences between the two groups of infants. However, the MCA differences were significant; measles P = 0.000, rubella P = 0.019. The MR vaccination of mothers may cause the prolongation of passive immunity in their infants, and may influence the immunogenicity of MMR vaccination. This finding should be considered for the optimal scheduling of the first dose of MMR vaccine. Also, the results showed that the immunogenicity of the rubella component of the MMR vaccine was lower than that reported.

  19. Biophysical and immunological studies on bovine immune globulins with evidence for selective transport within the mammary gland from maternal plasma to colostrum

    PubMed Central

    Pierce, A. E.; Feinstein, A.

    1965-01-01

    Three immune globulins in maternal serum and colostrum and newly born calf serum, have been characterized and compared. An examination was made to determine first, which of the maternal serum immune globulins accumulate in the circulation of the calf and secondly, the selectivity of the mammary gland for these proteins compared with the intestinal mucosa of the newly born calf. By difference in their electrophoretic mobilities three antigenically related immune globulins were isolated from bovine serum. The immune lactoglobulins in bovine colostrum were qualitatively similar to those in serum. However, marked differences were observed between the relative concentrations in serum and colostrum of the three immune globulins. An electrophoretically fast immune globulin (C1), present in colostrum at high concentration, was shown to be antigenically similar to an immune globulin (S1) present in the maternal serum at low concentration. These findings indicate that the mammary gland showed a highly selective preference for, and hence ability to concentrate in, colostrum, the electrophoretically fastest serum immune globulin. The slowest serum immune globulin and the component with intermediate electrophoretic mobility (S3 and S2 respectively) were both present at high concentration in bovine maternal serum, but were transmitted at different rates into the colostrum, so that the slowest serum immune globulin (S3) was present in the colostrum as a comparatively minor component (C3). In contrast to the mammary gland, the intestine of the newly born calf (permeable to undegraded protein during the first 24 hours of life) showed no selectivity. Immune globulins showing the three electrophoretic mobilities were absorbed equally readily. Thus, while the bovine mammary gland showed a highly selective preference for certain electrophoretically different serum proteins, no comparable selectivity was shown by the intestinal mucosa of the newly born calf. The results emphasize the

  20. Maternal work and children's diet, activity, and obesity.

    PubMed

    Datar, Ashlesha; Nicosia, Nancy; Shier, Victoria

    2014-04-01

    Mothers' work hours are likely to affect their time allocation towards activities related to children's diet, activity and well-being. For example, mothers who work more may be more reliant on processed foods, foods prepared away from home and school meal programs for their children's meals. A greater number of work hours may also lead to more unsupervised time for children that may, in turn, allow for an increase in unhealthy behaviors among their children such as snacking and sedentary activities such as TV watching. Using data on a national cohort of children, we examine the relationship between mothers' average weekly work hours during their children's school years on children's dietary and activity behaviors, BMI and obesity in 5th and 8th grade. Our results are consistent with findings from the literature that maternal work hours are positively associated with children's BMI and obesity especially among children with higher socioeconomic status. Unlike previous papers, our detailed data on children's behaviors allow us to speak directly to affected behaviors that may contribute to the increased BMI. We show that children whose mothers work more consume more unhealthy foods (e.g. soda, fast food) and less healthy foods (e.g. fruits, vegetables, milk) and watch more television. Although they report being slightly more physically active, likely due to organized physical activities, the BMI and obesity results suggest that the deterioration in diet and increase in sedentary behaviors dominate.

  1. Predicting future trends in the burden of pertussis in the 21st century: implications for infant pertussis and the success of maternal immunization.

    PubMed

    van den Biggelaar, Anita H J; Poolman, Jan T

    2016-01-01

    Support is growing for maternal immunization using acellular pertussis (aP) vaccines to prevent severe pertussis disease and deaths among very young, unvaccinated infants. Vaccine effectiveness of maternal immunization is 91% in preventing laboratory-confirmed pertussis in infants aged <3 months. To date, most mothers were primed in childhood with whole-cell pertussis vaccines. Soon, the generation of aP-primed individuals will become the new mothers-to-be. The shorter duration of protection afforded by aP vaccines, which is more pronounced with repeated aP boosters, may lead to increased pertussis circulation among aP-primed parents. Maternal Tdap immunization in aP-primed mothers-to-be may become less effective. Additional measures to protect young infants may eventually be needed, along with new vaccines that induce higher quality and more durable responses. PMID:26559122

  2. Knowledge, attitudes, beliefs, and behaviors of pregnant women approached to participate in a Tdap maternal immunization randomized, controlled trial.

    PubMed

    MacDougall, Donna M; Halperin, Beth A; Langley, Joanne M; McNeil, Shelly A; MacKinnon-Cameron, Donna; Li, Li; Halperin, Scott A

    2016-04-01

    Immunization with pertussis vaccine during pregnancy is recommended in a number of countries to prevent newborn deaths from whooping cough. In some jurisdictions, vaccine uptake during pregnancy is low. We undertook a survey of the knowledge, attitudes, beliefs, and behaviors of pregnant women who had been approached to participate in a randomized, controlled trial of tetanus-diphtheria-acellular pertussis (Tdap) vaccine during pregnancy. A total of 346 women completed the survey. Knowledge about pertussis and pertussis vaccine was generally low; the mean number of correct answers was 10.65 out of 19 questions. Attitudes toward maternal immunization were generally favorable; 51.7%-94.7% of women had positive responses to 10 attitudinal statements. Substantial uncertainty was shown in responses to a number of the attitudinal statements related to vaccination during pregnancy; 22.3%-45.7% neither agreed nor disagreed with the statements. Importantly, 89% of women reported that they would get immunized with pertussis vaccine during pregnancy if their physician recommended it. We conclude that a national recommendation to be immunized with pertussis vaccine during pregnancy supported by their physicians' recommendation would be well received by Canadian women. PMID:27176822

  3. Knowledge, attitudes, beliefs, and behaviors of pregnant women approached to participate in a Tdap maternal immunization randomized, controlled trial

    PubMed Central

    MacDougall, Donna M.; Halperin, Beth A.; Langley, Joanne M.; McNeil, Shelly A.; MacKinnon-Cameron, Donna; Li, Li; Halperin, Scott A.

    2016-01-01

    ABSTRACT Immunization with pertussis vaccine during pregnancy is recommended in a number of countries to prevent newborn deaths from whooping cough. In some jurisdictions, vaccine uptake during pregnancy is low. We undertook a survey of the knowledge, attitudes, beliefs, and behaviors of pregnant women who had been approached to participate in a randomized, controlled trial of tetanus-diphtheria-acellular pertussis (Tdap) vaccine during pregnancy. A total of 346 women completed the survey. Knowledge about pertussis and pertussis vaccine was generally low; the mean number of correct answers was 10.65 out of 19 questions. Attitudes toward maternal immunization were generally favorable; 51.7%–94.7% of women had positive responses to 10 attitudinal statements. Substantial uncertainty was shown in responses to a number of the attitudinal statements related to vaccination during pregnancy; 22.3%–45.7% neither agreed nor disagreed with the statements. Importantly, 89% of women reported that they would get immunized with pertussis vaccine during pregnancy if their physician recommended it. We conclude that a national recommendation to be immunized with pertussis vaccine during pregnancy supported by their physicians' recommendation would be well received by Canadian women. PMID:27176822

  4. Maternal exposure to fish oil primes offspring to harbor intestinal pathobionts associated with altered immune cell balance.

    PubMed

    Gibson, D L; Gill, S K; Brown, K; Tasnim, N; Ghosh, S; Innis, S; Jacobson, K

    2015-01-01

    Our previous studies revealed that offspring from rat dams fed fish oil (at 8% and 18% energy), developed impaired intestinal barriers sensitizing the colon to exacerbated injury later in life. To discern the mechanism, we hypothesized that in utero exposure to fish oil, rich in n-3 polyunsaturated fatty acid (PUFA), caused abnormal intestinal reparative responses to mucosal injury through differences in intestinal microbiota and the presence of naïve immune cells. To identify such mechanisms, gut microbes and naïve immune cells were compared between rat pups born to dams fed either n-6 PUFA, n-3 PUFA or breeder chow. Maternal exposure to either of the PUFA rich diets altered the development of the intestinal microbiota with an overall reduction in microbial density. Using qPCR, we found that each type of PUFA differentially altered the major gut phyla; fish oil increased Bacteroidetes and safflower oil increased Firmicutes. Both PUFA diets reduced microbes known to dominate the infant gut like Enterobacteriaceae and Bifidobacteria spp. when compared to the chow group. Uniquely, maternal fish oil diets resulted in offspring showing blooms of opportunistic pathogens like Bilophila wadsworthia, Enterococcus faecium and Bacteroides fragilis in their gut microbiota. As well, fish oil groups showed a reduction in colonic CD8+ T cells, CD4+ Foxp3+ T cells and arginase+ M2 macrophages. In conclusion, fish oil supplementation in pharmacological excess, at 18% by energy as shown in this study, provides an example where excess dosing in utero can prime offspring to harbor intestinal pathobionts and alter immune cell homeostasis. PMID:25559197

  5. The impact of maternal infection with Mycobacterium tuberculosis on the infant response to bacille Calmette-Guérin immunization.

    PubMed

    Mawa, Patrice A; Nkurunungi, Gyaviira; Egesa, Moses; Webb, Emily L; Smith, Steven G; Kizindo, Robert; Akello, Mirriam; Lule, Swaib A; Muwanga, Moses; Dockrell, Hazel M; Cose, Stephen; Elliott, Alison M

    2015-06-19

    Bacille Calmette-Guérin (BCG) immunization provides variable protection against tuberculosis. Prenatal antigen exposure may have lifelong effects on responses to related antigens and pathogens. We therefore hypothesized that maternal latent Mycobacterium tuberculosis infection (LTBI) influences infant responses to BCG immunization at birth. We measured antibody (n = 53) and cellular (n = 31) responses to M. tuberculosis purified protein derivative (PPD) in infants of mothers with and without LTBI, in cord blood and at one and six weeks after BCG. The concentrations of PPD-specific antibodies declined between birth (median [interquartile range (IQR)]) 5600 ng ml(-1) [3300-11 050] in cord blood) and six weeks (0.00 ng ml(-1) [0-288]). Frequencies of PPD-specific IFN-γ-expressing CD4(+)T cells increased at one week and declined between one and six weeks (p = 0.031). Frequencies of IL-2- and TNF-α-expressing PPD-specific CD4(+)T cells increased between one and six weeks (p = 0.019, p = 0.009, respectively). At one week, the frequency of PPD-specific CD4(+)T cells expressing any of the three cytokines, combined, was lower among infants of mothers with LTBI, in crude analyses (p = 0.002) and after adjusting for confounders (mean difference, 95% CI -0.041% (-0.082, -0.001)). In conclusion, maternal LTBI was associated with lower infant anti-mycobacterial T-cell responses immediately following BCG immunization. These findings are being explored further in a larger study.

  6. The impact of maternal infection with Mycobacterium tuberculosis on the infant response to bacille Calmette–Guérin immunization

    PubMed Central

    Mawa, Patrice A.; Nkurunungi, Gyaviira; Egesa, Moses; Webb, Emily L.; Smith, Steven G.; Kizindo, Robert; Akello, Mirriam; Lule, Swaib A.; Muwanga, Moses; Dockrell, Hazel M.; Cose, Stephen; Elliott, Alison M.

    2015-01-01

    Bacille Calmette–Guérin (BCG) immunization provides variable protection against tuberculosis. Prenatal antigen exposure may have lifelong effects on responses to related antigens and pathogens. We therefore hypothesized that maternal latent Mycobacterium tuberculosis infection (LTBI) influences infant responses to BCG immunization at birth. We measured antibody (n = 53) and cellular (n = 31) responses to M. tuberculosis purified protein derivative (PPD) in infants of mothers with and without LTBI, in cord blood and at one and six weeks after BCG. The concentrations of PPD-specific antibodies declined between birth (median [interquartile range (IQR)]) 5600 ng ml−1 [3300–11 050] in cord blood) and six weeks (0.00 ng ml−1 [0–288]). Frequencies of PPD-specific IFN-γ-expressing CD4+T cells increased at one week and declined between one and six weeks (p = 0.031). Frequencies of IL-2- and TNF-α-expressing PPD-specific CD4+T cells increased between one and six weeks (p = 0.019, p = 0.009, respectively). At one week, the frequency of PPD-specific CD4+T cells expressing any of the three cytokines, combined, was lower among infants of mothers with LTBI, in crude analyses (p = 0.002) and after adjusting for confounders (mean difference, 95% CI −0.041% (−0.082, −0.001)). In conclusion, maternal LTBI was associated with lower infant anti-mycobacterial T-cell responses immediately following BCG immunization. These findings are being explored further in a larger study. PMID:25964450

  7. Prenatal immune activation causes hippocampal synaptic deficits in the absence of overt microglia anomalies.

    PubMed

    Giovanoli, Sandra; Weber-Stadlbauer, Ulrike; Schedlowski, Manfred; Meyer, Urs; Engler, Harald

    2016-07-01

    Prenatal exposure to infectious or inflammatory insults can increase the risk of developing neuropsychiatric disorder in later life, including schizophrenia, bipolar disorder, and autism. These brain disorders are also characterized by pre- and postsynaptic deficits. Using a well-established mouse model of maternal exposure to the viral mimetic polyriboinosinic-polyribocytidilic acid [poly(I:C)], we examined whether prenatal immune activation might cause synaptic deficits in the hippocampal formation of pubescent and adult offspring. Based on the widely appreciated role of microglia in synaptic pruning, we further explored possible associations between synaptic deficits and microglia anomalies in offspring of poly(I:C)-exposed and control mothers. We found that prenatal immune activation induced an adult onset of presynaptic hippocampal deficits (as evaluated by synaptophysin and bassoon density). The early-life insult further caused postsynaptic hippocampal deficits in pubescence (as evaluated by PSD95 and SynGAP density), some of which persisted into adulthood. In contrast, prenatal immune activation did not change microglia (or astrocyte) density, nor did it alter their activation phenotypes. The prenatal manipulation did also not cause signs of persistent systemic inflammation. Despite the absence of overt glial anomalies or systemic inflammation, adult offspring exposed to prenatal immune activation displayed increased hippocampal IL-1β levels. Taken together, our findings demonstrate that age-dependent synaptic deficits and abnormal pro-inflammatory cytokine expression can occur during postnatal brain maturation in the absence of microglial anomalies or systemic inflammation.

  8. Maternal transmission of immunity to Eimeria maxima: enzyme-linked immunosorbent assay analysis of protective antibodies induced by infection.

    PubMed Central

    Smith, N C; Wallach, M; Miller, C M; Morgenstern, R; Braun, R; Eckert, J

    1994-01-01

    , the levels of immunoglobulin G (IgG) antibodies to all developmental stages in yolks or hatchling sera were very strongly correlated with maternally derived immunity to E. maxima. In contrast, parasite-specific IgM or IgA was not detectable, either in egg yolk or egg white. These results demonstrate the ability of IgG antibodies to protect against E. maxima in poultry, thus raising the possibility of using protective maternally derived IgG antibodies to identify potentially protective parasite antigens and indicating the feasibility of using maternal immunization as a means for parasite control. PMID:8132342

  9. Prenatal acetaminophen affects maternal immune and endocrine adaptation to pregnancy, induces placental damage, and impairs fetal development in mice.

    PubMed

    Thiele, Kristin; Solano, M Emilia; Huber, Samuel; Flavell, Richard A; Kessler, Timo; Barikbin, Roja; Jung, Roman; Karimi, Khalil; Tiegs, Gisa; Arck, Petra C

    2015-10-01

    Acetaminophen (APAP; ie, Paracetamol or Tylenol) is generally self-medicated to treat fever or pain and recommended to pregnant women by their physicians. Recent epidemiological studies reveal an association between prenatal APAP use and an increased risk for asthma. Our aim was to identify the effects of APAP in pregnancy using a mouse model. Allogeneically mated C57Bl/6J females were injected i.p. with 50 or 250 mg/kg APAP or phosphate-buffered saline on gestation day 12.5; nonpregnant females served as controls. Tissue samples were obtained 1 or 4 days after injection. APAP-induced liver toxicity was mirrored by significantly increased plasma alanine aminotransferase levels. In uterus-draining lymph nodes of pregnant dams, the frequencies of mature dendritic cells and regulatory T cells significantly increased on 250 mg/kg APAP. Plasma progesterone levels significantly decreased in dams injected with APAP, accompanied by a morphologically altered placenta. Although overall litter sizes and number of fetal loss remained unaltered, a reduced fetal weight and a lower frequency of hematopoietic stem cells in the fetal liver were observed on APAP treatment. Our data provide strong evidence that prenatal APAP interferes with maternal immune and endocrine adaptation to pregnancy, affects placental function, and impairs fetal maturation and immune development. The latter may have long-lasting consequences on children's immunity and account for the increased risk for asthma observed in humans. PMID:26254283

  10. Prenatal acetaminophen affects maternal immune and endocrine adaptation to pregnancy, induces placental damage, and impairs fetal development in mice.

    PubMed

    Thiele, Kristin; Solano, M Emilia; Huber, Samuel; Flavell, Richard A; Kessler, Timo; Barikbin, Roja; Jung, Roman; Karimi, Khalil; Tiegs, Gisa; Arck, Petra C

    2015-10-01

    Acetaminophen (APAP; ie, Paracetamol or Tylenol) is generally self-medicated to treat fever or pain and recommended to pregnant women by their physicians. Recent epidemiological studies reveal an association between prenatal APAP use and an increased risk for asthma. Our aim was to identify the effects of APAP in pregnancy using a mouse model. Allogeneically mated C57Bl/6J females were injected i.p. with 50 or 250 mg/kg APAP or phosphate-buffered saline on gestation day 12.5; nonpregnant females served as controls. Tissue samples were obtained 1 or 4 days after injection. APAP-induced liver toxicity was mirrored by significantly increased plasma alanine aminotransferase levels. In uterus-draining lymph nodes of pregnant dams, the frequencies of mature dendritic cells and regulatory T cells significantly increased on 250 mg/kg APAP. Plasma progesterone levels significantly decreased in dams injected with APAP, accompanied by a morphologically altered placenta. Although overall litter sizes and number of fetal loss remained unaltered, a reduced fetal weight and a lower frequency of hematopoietic stem cells in the fetal liver were observed on APAP treatment. Our data provide strong evidence that prenatal APAP interferes with maternal immune and endocrine adaptation to pregnancy, affects placental function, and impairs fetal maturation and immune development. The latter may have long-lasting consequences on children's immunity and account for the increased risk for asthma observed in humans.

  11. Exposure to Maternal Distress in Childhood and Cortisol Activity in Young Adulthood

    ERIC Educational Resources Information Center

    Mahrer, Nicole E.; Luecken, Linda J.; Wolchik, Sharlene A.; Tein, Jenn-Yun; Sandler, Irwin N.

    2014-01-01

    Dysregulated cortisol is a risk factor for poor health outcomes. Children of distressed mothers exhibit dysregulated cortisol, yet it is unclear whether maternal distress predicts cortisol activity in later developmental stages. This longitudinal study examined the prospective relation between maternal distress during late childhood (9-12 years)…

  12. Commensal bacteria calibrate the activation threshold of innate antiviral immunity.

    PubMed

    Abt, Michael C; Osborne, Lisa C; Monticelli, Laurel A; Doering, Travis A; Alenghat, Theresa; Sonnenberg, Gregory F; Paley, Michael A; Antenus, Marcelo; Williams, Katie L; Erikson, Jan; Wherry, E John; Artis, David

    2012-07-27

    Signals from commensal bacteria can influence immune cell development and susceptibility to infectious or inflammatory diseases. However, the mechanisms by which commensal bacteria regulate protective immunity after exposure to systemic pathogens remain poorly understood. Here, we demonstrate that antibiotic-treated (ABX) mice exhibit impaired innate and adaptive antiviral immune responses and substantially delayed viral clearance after exposure to systemic LCMV or mucosal influenza virus. Furthermore, ABX mice exhibited severe bronchiole epithelial degeneration and increased host mortality after influenza virus infection. Genome-wide transcriptional profiling of macrophages isolated from ABX mice revealed decreased expression of genes associated with antiviral immunity. Moreover, macrophages from ABX mice exhibited defective responses to type I and type II IFNs and impaired capacity to limit viral replication. Collectively, these data indicate that commensal-derived signals provide tonic immune stimulation that establishes the activation threshold of the innate immune system required for optimal antiviral immunity.

  13. The Effect of Maternal Teaching Talk on Children's Emergent Literacy as a Function of Type of Activity and Maternal Education Level

    ERIC Educational Resources Information Center

    Korat, Ofra

    2009-01-01

    This study examined the extent to which maternal education affects mothers' teaching talk level as a function of activity (book reading vs. looking at a family photo album), and the contribution of maternal teaching talk level during these activities to 88 five- to six-year old children's emergent literacy. Videotaped mother-child interactions…

  14. Regulatory dendritic cells: there is more than just immune activation

    PubMed Central

    Schmidt, Susanne V.; Nino-Castro, Andrea C.; Schultze, Joachim L.

    2012-01-01

    The immune system exists in a delicate equilibrium between inflammatory responses and tolerance. This unique feature allows the immune system to recognize and respond to potential threats in a controlled but normally limited fashion thereby preventing a destructive overreaction against healthy tissues. While the adaptive immune system was the major research focus concerning activation vs. tolerance in the immune system more recent findings suggest that cells of the innate immune system are important players in the decision between effective immunity and induction of tolerance or immune inhibition. Among immune cells of the innate immune system dendritic cells (DCs) have a special function linking innate immune functions with the induction of adaptive immunity. DCs are the primary professional antigen presenting cells (APCs) initiating adaptive immune responses. They belong to the hematopoietic system and arise from CD34+ stem cells in the bone marrow. Particularly in the murine system two major subgroups of DCs, namely myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) can be distinguished. DCs are important mediators of innate and adaptive immunity mostly due to their remarkable capacity to present processed antigens via major histocompatibility complexes (MHC) to T cells and B cells in secondary lymphoid organs. A large body of literature has been accumulated during the last two decades describing which role DCs play during activation of T cell responses but also during the establishment and maintenance of central tolerance (Steinman et al., 2003). While the concept of peripheral tolerance has been clearly established during the last years, the role of different sets of DCs and their particular molecular mechanisms of immune deviation has not yet fully been appreciated. In this review we summarize accumulating evidence about the role of regulatory DCs in situations where the balance between tolerance and immunogenicity has been altered leading to pathologic

  15. Viral competition and maternal immunity influence the clinical disease caused by very virulent infectious bursal disease virus.

    PubMed

    Jackwood, Daral J

    2011-09-01

    The very virulent form of infectious bursal disease virus (vvIBDV) causes an immunosuppressive disease that is further characterized by the rapid onset of morbidity and high mortality in susceptible chickens. In 2009, vvIBDV was first reported in California, U. S. A., and since that time only a few cases of acute infectious bursal disease attributed to vvIBDV have been recognized in California. In other countries where vvIBDV has become established, it rapidly spreads to most poultry-producing regions. Two factors that may be involved in limiting the spread or reducing the severity of the clinical disease caused by vvIBDV in the U. S. A. are maternal immunity and competition with endemic variant strains of the virus. In this study, the ability of vvIBDV to infect and cause disease in maternally immune layer chickens was examined at weekly intervals over a 5-wk period during which their neutralizing maternal antibodies waned. Birds inoculated with vvIBDV at 2, 3, and 4 wk of age seemed healthy throughout the duration of the experiment, but macroscopic and microscopic lesions were observed in their bursa tissues. A real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay also confirmed the presence of vvIBDV RNA in their bursa tissues, indicating this virus was infecting the birds even at 2 wk of age when neutralizing maternal antibodies to infectious bursal disease virus were still relatively high (> 2000 geometric mean antibody titer). No mortality was observed in any birds when inoculated at 2, 3, or 4 wk of age; however, inoculation at 5 and 6 wk of age resulted in 10% and 20% mortality, respectively. Three experiments on the competition between vvIBDV and the two variant viruses T1 and FF6 were conducted. In all three experiments, specific-pathogen-free (SPF) birds that were inoculated with only the vvIBDV became acutely moribund, and except for Experiment 1 (62% mortality) all succumbed to the infection within 4 days of being exposed. When the

  16. IMMUNE ACTIVATION AND PAEDIATRIC HIV-1 DISEASE OUTCOME

    PubMed Central

    Roider, J; Muenchhoff, M; Goulder, PJR

    2016-01-01

    Purpose of review The paediatric HIV epidemic is changing. Over the past decade, new infections have substantially reduced whilst access to antiretroviral therapy (ART) has increased. Overall this success means that numbers of children living with HIV are climbing. In addition, the problems in adults of chronic inflammation resulting from persistent immune activation even following ART-mediated suppression of viral replication are magnified in children infected from birth. Recent findings Features of immune ontogeny favor low immune activation in early life, whilst specific aspects of paediatric HIV infection tend to increase it. A subset of ART-naïve non-progressing children exists in whom normal CD4 counts are maintained in the setting of persistent high viremia and yet in the context of low immune activation. This sooty mangabey-like phenotype contrasts with non-progressing adult infection characterized by the expression of protective HLA class I molecules and low viral load. The particular factors contributing to raised or lowered immune activation in paediatric infection, and that ultimately influence disease outcome, are discussed. Summary Novel strategies to circumvent the unwanted long-term consequences of HIV infection may be possible in children in whom natural immune ontogeny in early life militates against immune activation. Defining the mechanisms underlying low immune activation in natural HIV infection would have applications beyond paediatric HIV. PMID:26679413

  17. Maternal and fetal immune response patterns in heifers experimentally infected with Neospora caninum in the second trimester of pregnancy- A descriptive study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fetal and maternal immune responses 3, 6 and 9 weeks post infection (wpi) were investigated in cows experimentally infected with Neospora caninum on day 110 of gestation. Descriptive analysis showed that the fetuses had lower percentages of spleen T cell subpopulations (CD3+, CD4+ and CD8+) at 6 wpi...

  18. Maternal and foetal immune responses of cattle following an experimental challenge with Neospora caninum at day 70 of gestation

    PubMed Central

    2012-01-01

    The immune responses of pregnant cattle and their foetuses were examined following inoculation on day 70 of gestation either intravenously (iv) (group 1) or subcutaneously (sc) (group 2) with live NC1 strain tachyzoites or with Vero cells (control) (group 3). Peripheral blood mononuclear cell (PBMC) responses to Neospora antigen and foetal viability were assessed throughout the experiment. Two animals from each group were sacrificed at 14, 28, 42 and 56 days post inoculation (pi). At post mortem, maternal lymph nodes, spleen and PBMC and when possible foetal spleen, thymus and PBMC samples were collected for analysis. Inoculation with NC1 (iv and sc) lead to foetal deaths in all group 1 dams (6/6) and in 3/6 group 2 dams from day 28pi; statistically significant (p ≤ 0.05) increases in cell-mediated immune (CMI) responses including antigen-specific cell proliferation and IFN-γ production as well as increased levels of IL-4, IL-10 and IL-12 were observed in challenged dams compared to the group 3 animals. Lymph node samples from the group 2 animals carrying live foetuses showed greater levels of cellular proliferation as well as significantly (p ≤ 0.05) higher levels of IFN-γ compared to the dams in group 2 carrying dead foetuses. Foetal spleen, thymus and PBMC samples demonstrated cellular proliferation as well as IFN-γ, IL-4, IL-10 and IL-12 production following mitogenic stimulation with Con A from day 14pi (day 84 gestation) onwards. This study shows that the generation of robust peripheral and local maternal CMI responses (lymphoproliferation, IFN-γ) may inhibit the vertical transmission of the parasite. PMID:22536795

  19. Immunization therapy for Alzheimer disease: a comprehensive review of active immunization strategies.

    PubMed

    Tabira, Takeshi

    2010-02-01

    Based on the amyloid cascade hypothesis, various strategies targeting amyloid beta protein (Abeta) have been invented for prevention and treatment of Alzheimer disease (AD). Active and passive immunizations with Abeta and Abeta antibodies successfully reduced AD pathology and improved cognitive functions in an AD mouse model. However, active immunization with AN-1792, a mixture of Abeta1-42 peptide and adjuvant QS21 induced autoimmune encephalitis in humans. Surprisingly, although AN-1792 cleared senile plaque amyloid, it showed no benefit in humans. It is speculated that AN-1792 failed in deleting more toxic forms of Abeta such as oligomers and intracellular Abeta, suggesting that newly developing vaccines should delete these toxic molecules. Since T cell epitopes exist mainly in the C-terminal portion of Abeta, vaccines using shorter N-terminal peptides are under development. In addition, since T helper 1 (Th1) immune responses activate encephalitogenic T cells and induce continuous inflammation in the central nervous system, vaccines inducing Th2 immune responses seem to be more promising. These are N-terminal short Abeta peptides with Th2 adjuvant or Th2-stimulating molecules, DNA vaccines, recombinant viral vector vaccines, recombinant vegetables and others. Improvement of vaccines will be also achieved by the administration method, because Th2 immune responses are mainly induced by mucosal or trans-cutaneous immunizations. Here I review recent progress in active immunization strategies for AD.

  20. Maternal Active and Passive Smoking and Hypertensive Disorders of Pregnancy

    PubMed Central

    Engel, Stephanie M.; Scher, Erica; Wallenstein, Sylvan; Savitz, David A.; Alsaker, Elin R.; Trogstad, Lill; Magnus, Per

    2014-01-01

    Background The inverse association between prenatal smoking and preeclampsia is puzzling, given the increased risks of prematurity and low birthweight associated with both smoking and preeclampsia. We analyzed the Norwegian Mother and Child Birth Cohort (MoBa) to determine whether the associations varied by timing of prenatal smoking. Methods We conducted an analysis of 74,439 singleton pregnancies with completed second- and third- trimester questionnaires. Active and passive smoke exposure by trimester were determined by maternal self-report, and covered the period of preconception through approximately 30 weeks’ gestation. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results Rates of active smoking declined dramatically during pregnancy: for trimester 1, 23%; trimester 2, 9%; and trimester 3, 8%. Active smoking in the third trimester was associated with reduced odds of preeclampsia and gestational hypertension, with the strongest association among continuous smokers (for preeclampsia, OR = 0.57 [95% CI = 0.46–0.70]). Women who quit smoking before the third trimester had approximately the same risk of preeclampsia and gestational hypertension as nonsmokers. There was some evidence of dose-response, with the heaviest smokers (more than eight cigarettes per day) having the lowest risks of preeclampsia (0.48 [0.32–0.73]) and gestational hypertension (0.51 [0.28–0.95]). There was little evidence of an association with passive smoking exposure. Conclusion The association between smoking and preeclampsia varies substantially according to the timing and intensity of exposure. A better understanding of the biologic pathways that underlie these associations may provide important clues to the etiology of preeclampsia and the development of effective clinical interventions. PMID:23429405

  1. Do Maternal Knowledge and Attitudes towards Childhood Immunizations in Rural Uganda Correlate with Complete Childhood Vaccination?

    PubMed

    Vonasek, Bryan J; Bajunirwe, Francis; Jacobson, Laura E; Twesigye, Leonidas; Dahm, James; Grant, Monica J; Sethi, Ajay K; Conway, James H

    2016-01-01

    Improving childhood vaccination coverage and timeliness is a key health policy objective in many developing countries such as Uganda. Of the many factors known to influence uptake of childhood immunizations in under resourced settings, parents' understanding and perception of childhood immunizations has largely been overlooked. The aims of this study were to survey mothers' knowledge and attitudes towards childhood immunizations and then determine if these variables correlate with the timely vaccination coverage of their children. From September to December 2013, we conducted a cross-sectional survey of 1,000 parous women in rural Sheema district in southwest Uganda. The survey collected socio-demographic data and knowledge and attitudes towards childhood immunizations. For the women with at least one child between the age of one month and five years who also had a vaccination card available for the child (N = 302), the vaccination status of this child was assessed. 88% of these children received age-appropriate, on-time immunizations. 93.5% of the women were able to state that childhood immunizations protect children from diseases. The women not able to point this out were significantly more likely to have an under-vaccinated child (PR 1.354: 95% CI 1.018-1.802). When asked why vaccination rates may be low in their community, the two most common responses were "fearful of side effects" and "ignorance/disinterest/laziness" (44% each). The factors influencing caregivers' demand for childhood immunizations vary widely between, and also within, developing countries. Research that elucidates local knowledge and attitudes, like this study, allows for decisions and policy pertaining to vaccination programs to be more effective at improving child vaccination rates. PMID:26918890

  2. Do Maternal Knowledge and Attitudes towards Childhood Immunizations in Rural Uganda Correlate with Complete Childhood Vaccination?

    PubMed

    Vonasek, Bryan J; Bajunirwe, Francis; Jacobson, Laura E; Twesigye, Leonidas; Dahm, James; Grant, Monica J; Sethi, Ajay K; Conway, James H

    2016-01-01

    Improving childhood vaccination coverage and timeliness is a key health policy objective in many developing countries such as Uganda. Of the many factors known to influence uptake of childhood immunizations in under resourced settings, parents' understanding and perception of childhood immunizations has largely been overlooked. The aims of this study were to survey mothers' knowledge and attitudes towards childhood immunizations and then determine if these variables correlate with the timely vaccination coverage of their children. From September to December 2013, we conducted a cross-sectional survey of 1,000 parous women in rural Sheema district in southwest Uganda. The survey collected socio-demographic data and knowledge and attitudes towards childhood immunizations. For the women with at least one child between the age of one month and five years who also had a vaccination card available for the child (N = 302), the vaccination status of this child was assessed. 88% of these children received age-appropriate, on-time immunizations. 93.5% of the women were able to state that childhood immunizations protect children from diseases. The women not able to point this out were significantly more likely to have an under-vaccinated child (PR 1.354: 95% CI 1.018-1.802). When asked why vaccination rates may be low in their community, the two most common responses were "fearful of side effects" and "ignorance/disinterest/laziness" (44% each). The factors influencing caregivers' demand for childhood immunizations vary widely between, and also within, developing countries. Research that elucidates local knowledge and attitudes, like this study, allows for decisions and policy pertaining to vaccination programs to be more effective at improving child vaccination rates.

  3. Do Maternal Knowledge and Attitudes towards Childhood Immunizations in Rural Uganda Correlate with Complete Childhood Vaccination?

    PubMed Central

    Vonasek, Bryan J.; Bajunirwe, Francis; Jacobson, Laura E.; Twesigye, Leonidas; Dahm, James; Grant, Monica J.; Sethi, Ajay K.; Conway, James H.

    2016-01-01

    Improving childhood vaccination coverage and timeliness is a key health policy objective in many developing countries such as Uganda. Of the many factors known to influence uptake of childhood immunizations in under resourced settings, parents’ understanding and perception of childhood immunizations has largely been overlooked. The aims of this study were to survey mothers’ knowledge and attitudes towards childhood immunizations and then determine if these variables correlate with the timely vaccination coverage of their children. From September to December 2013, we conducted a cross-sectional survey of 1,000 parous women in rural Sheema district in southwest Uganda. The survey collected socio-demographic data and knowledge and attitudes towards childhood immunizations. For the women with at least one child between the age of one month and five years who also had a vaccination card available for the child (N = 302), the vaccination status of this child was assessed. 88% of these children received age-appropriate, on-time immunizations. 93.5% of the women were able to state that childhood immunizations protect children from diseases. The women not able to point this out were significantly more likely to have an under-vaccinated child (PR 1.354: 95% CI 1.018–1.802). When asked why vaccination rates may be low in their community, the two most common responses were “fearful of side effects” and “ignorance/disinterest/laziness” (44% each). The factors influencing caregivers’ demand for childhood immunizations vary widely between, and also within, developing countries. Research that elucidates local knowledge and attitudes, like this study, allows for decisions and policy pertaining to vaccination programs to be more effective at improving child vaccination rates. PMID:26918890

  4. Maternal autoantibodies in autism.

    PubMed

    Braunschweig, Daniel; Van de Water, Judy

    2012-06-01

    As epidemiologic studies continue to note a striking increase in rates of autism spectrum disorder (ASD) diagnosis around the world, the lack of identified causative agents in most cases remains a major hindrance to the development of treatment and prevention strategies. Published observations of immune system abnormalities in ASD have increased recently, with several groups identifying fetal protein reactive IgG antibodies in plasma from mothers of children with autism. Furthermore, other gestational immune parameters, including maternal infection and dysregulated cytokine signaling, have been found to be associated with ASD in some cases. While detailed pathogenic mechanisms remain to be determined, the hypothesis that some cases of ASD may be influenced, or even caused, by maternal fetal brain-reactive antibodies or other in utero immune-related exposures is an active area of investigation. This article reviews the current literature in this area and proposes several directions for future research.

  5. Adolescent voluntary exercise attenuated hippocampal innate immunity responses and depressive-like behaviors following maternal separation stress in male rats.

    PubMed

    Sadeghi, Mahsa; Peeri, Maghsoud; Hosseini, Mir-Jamal

    2016-09-01

    Early life stressful events have detrimental effects on the brain and behavior, which are associated with the development of depression. Immune-inflammatory responses have been reported to contribute in the pathophysiology of depression. Many studies have reported on the beneficial effects of exercise against stress. However, underlying mechanisms through which exercise exerts its effects were poorly studied. Therefore, it applied maternal separation (MS), as a valid animal model of early-life adversity, in rats from postnatal day (PND) 2 to 14 for 180min per day. At PND 28, male Wistar albino rats were subjected to 5 experimental groups; 1) controls 2) MS rats 3) MS rats treated with fluoxetine 5mg/kg to PND 60, 4) MS rats that were subjected to voluntary running wheel (RW) exercise and 5) MS rats that were subjected to mandatory treadmill (TM) exercise until adulthood. At PND 60, depressive-like behaviors were assessed by using forced swimming test (FST), splash test, and sucrose preference test (SPT). Our results revealed that depressive-like behaviors following MS stress were associated with an increase in expression of toll-like receptor 4 (Tlr-4) and its main signaling protein, Myd88, in the hippocampal formation. Also, we found that voluntary (and not mandatory) physical exercise during adolescence is protected against depressant effects of early-life stress at least partly through mitigating the innate immune responses in the hippocampus. PMID:27184238

  6. Maternal autonomy and attitudes towards gender norms: associations with childhood immunization in Nigeria.

    PubMed

    Singh, Kavita; Haney, Erica; Olorunsaiye, Comfort

    2013-07-01

    Globally 2.5 million children under-five die from vaccine preventable diseases, and in Nigeria only 23 % of children ages 12-23 months are fully immunized. The international community is promoting gender equality as a means to improve the health and well-being of women and their children. This paper looks at whether measures of gender equality, autonomy and individual attitudes towards gender norms, are associated with a child being fully immunized in Nigeria. Data from currently married women with a child 12-23 months from the 2008 Nigeria demographic and health survey were used to study the influence of autonomy and gender attitudes on whether or not a child is fully immunized. Multivariate logistic regression was used and several key socioeconomic variables were controlled for including wealth and education, which are considered key inputs into gender equality. Findings indicated that household decision-making and attitudes towards wife beating were significantly associated with a child being fully immunized after controlling for socioeconomic variables. Ethnicity, wealth and education were also significant factors. Programmatic and policy implications indicate the potential for the promotion of gender equality as a means to improve child health. Gender equality can be seen as a means to enable women to access life-saving services for their children.

  7. Development of maternal and foetal immune responses in cattle following experimental challenge with Neospora caninum at day 210 of gestation

    PubMed Central

    2013-01-01

    This study examined the immunological responses of pregnant cattle and their foetuses following an experimental challenge with live Neospora caninum tachyzoites at day 210 of gestation. Animals were bled prior to and weekly throughout the experiment and sacrificed at 14, 28, 42 and 56 days post inoculation (dpi). At post mortem examination, samples of lymph nodes and spleen were collected from both dam and foetus for immunological analysis. Subcutaneous (sc) inoculation over the left prefemoral (LPF) lymph node of pregnant cattle at day 210 of gestation, led to the vertical transmission of parasites by 14 dpi, however no foetal deaths were observed in the infected animals. Foetuses from infected dams mounted Neospora-specific humoral and cell-mediated immune (CMI) responses by 14 dpi. These responses involved anti-Neospora IgG, antigen-specific lymphocyte proliferation, and the production of the cytokines IFN–γ, interleukin (IL)-4 and IL-10. There was also evidence of innate immunity during the response against Neospora from infected dams, with statistically significant (p < 0.05) increases in mean expression of toll like receptors (TLR)-2 on 56 dpi in maternal spleen, LPF, right prefemoral (RPF), left uterine (LUL) and right uterine (RUL) lymph nodes and TLR-9 in retropharyngeal (RLN), LPF and RPF lymph nodes from 28 dpi. Statistically significant (p < 0.05) increases in mean TLR-9 were detected in spleen samples from foetuses of infected dams, compared to the foetuses from control animals. Our results show that vertical transmission of the parasite occurred in all infected dams, with their foetuses showing effective Neospora-specific cell mediated, humoral and innate immune responses. PMID:24090114

  8. Experimental study of the maternal effects on tumor immunity of infant mice with C1300 mouse neuroblastoma.

    PubMed

    Sakamoto, I; Kawakatsu, H; Kidowaki, T; Matumura, T; Sugimoto, T; Sawada, T

    1988-04-01

    The spontaneous regression of neuroblastoma (NB), one of the most common malignant tumors in childhood, is found to occur in 1% to 2% of patients with NB, especially in young infants. An unexpectedly favorable response to therapy is also noticed in infants suggesting the potential presence of an immune mechanism. Monoclonal C1300-S and C1300A-4 cell lines were established from polyclonal C1300 cells in our laboratory. Adult female A/J mice that had rejected 1 x 10(3) NB cells (C1300S-3) or 1 x 10(5)-10(6) NB cells (C1300A-4) were used as immunized mothers. The immunized mothers with C1300A-4 or C1300S-3 were found to have specific antibodies to C1300S-3 cells by 51Cr release assay of complement dependent cytotoxicity. Newborn mice, 24 hours after birth from immunized or nonimmunized mothers, were inoculated with 1 x 10(3) C1300S-3 NB cells. The same antibody that was assayed in the immunized mothers was detected in this offspring by the antibody-dependent cell cytotoxicity (ADCC). The tumor incidence in the offspring of the immunized mothers was found to be less than that of the offspring of the nonimmunized mothers. This study suggests that the lower tumor incidence in the offspring of immunized mothers compared with offspring of nonimmunized mothers may be attributed to their ADCC activity. Furthermore, the antibody that has the ADCC activity was proven to be immunoglobulin G by a serum absorption test using IgG absorbant. This study offers insight into the relationship between transported mother-infant immunoglobulins and on its potential control of NB.

  9. The influence of culture on maternal soothing behaviours and infant pain expression in the immunization context

    PubMed Central

    Vinall, Jillian; Pillai Riddell, Rebecca; Greenberg, Saul

    2011-01-01

    OBJECTIVE: To investigate how maternal culture (ie, individualist versus collectivist) influences soothing techniques and infant distress. METHODS: Archival data were analyzed using a subsample of 80 mother-infant dyads selected from a larger database of infant pain expression. RESULTS: Mothers belonging to the individualist group used more affection behaviours when attempting to regulate their infants’ distress. No differences were observed in mothers’ touching, holding, rocking, vocalizing, caregiving or distracting their infants. Mothers’ culture did not appear to be related to the level of distress expressed by their infants. CONCLUSIONS: These results suggest that the similarities in soothing and infant pain expression between individualist and collectivist cultures are more prominent than their differences. PMID:22059192

  10. Breastfeeding, Brain Activation to Own Infant Cry, and Maternal Sensitivity

    ERIC Educational Resources Information Center

    Kim, Pilyoung; Feldman, Ruth; Mayes, Linda C.; Eicher, Virginia; Thompson, Nancy; Leckman, James F.; Swain, James E.

    2011-01-01

    Background: Research points to the importance of breastfeeding for promoting close mother-infant contact and social-emotional development. Recent functional magnetic resonance imaging (fMRI) studies have identified brain regions related to maternal behaviors. However, little research has addressed the neurobiological mechanisms underlying the…

  11. Active immunization by a dengue virus-induced cytokine.

    PubMed Central

    Chaturvedi, U C; Mukerjee, R; Dhawan, R

    1994-01-01

    Dengue type 2 virus (DV)-induced cytotoxic factor (CF) is capable of reproducing various pathological lesions in mice that are seen in human dengue. The present study was undertaken to investigate the protective effect of active immunization of mice with CF. Mice were immunized with 5 microgram of CF and prevention of CF-induced increase in capillary permeability and damage to the blood-brain barrier were studied at weekly intervals, up to 48 weeks, by challenging with 3 microgram of CF. Maximum protection against increase in capillary permeability and damage to the blood-brain barrier was observed in week 4 after immunization. A breakthrough in the protection occurred with higher doses of CF in a dose-dependent manner. Challenge with a lethal intracerebral (i.c.) dose of DV showed significantly prolonged mean survival time and delayed onset of symptoms of sickness in the immunized mice compared with the normal mice, but the titre of the virus in the brain was similar in the two groups. On i.p. challenge with the virus the protection against damage to the blood-brain barrier was 86 +/- 7% at week 4 and 17 +/- 4% at week 26 after immunization. Sera obtained from the immunized mice showed the presence of CF-specific antibodies by ELISA, Western blot, and by neutralization of the cytotoxic activity of CF in vitro. The present study describes successful prevention of a cytokine-induced pathology by specific active immunization. PMID:8187327

  12. [Bone marrow stromal damage mediated by immune response activity].

    PubMed

    Vojinović, J; Kamenov, B; Najman, S; Branković, Lj; Dimitrijević, H

    1994-01-01

    The aim of this work was to estimate influence of activated immune response on hematopoiesis in vitro, using the experimental model of BCG immunized BALB/c mice and in patients with chronic immunoactivation: long-lasting infections, autoimmunity or malignancy. We correlated changes in long term bone marrow cultures (Dexter) and NBT reduction with appearance of anemia in patients and experimental model of immunization by BCG. Increased spontaneous NBT reduction pointed out role of macrophage activation in bone marrow stroma damage. Long-term bone marrow cultures showed reduced number of hematopoietic cells, with predomination of fibroblasts and loss of fat cells. This results correlated with anemia and leucocytosis with stimulated myelopoiesis in peripheral blood. Activation of immune response, or acting of any agent that directly changes extracellular matrix and cellularity of bone marrow, may result in microenviroment bone marrow damage that modify hematopoiesis.

  13. Human HLA-G+ extravillous trophoblasts: Immune-activating cells that interact with decidual leukocytes.

    PubMed

    Tilburgs, Tamara; Crespo, Ângela C; van der Zwan, Anita; Rybalov, Basya; Raj, Towfique; Stranger, Barbara; Gardner, Lucy; Moffett, Ashley; Strominger, Jack L

    2015-06-01

    Invading human leukocyte antigen-G+ (HLA-G+) extravillous trophoblasts (EVT) are rare cells that are believed to play a key role in the prevention of a maternal immune attack on foreign fetal tissues. Here highly purified HLA-G+ EVT and HLA-G- villous trophoblasts (VT) were isolated. Culture on fibronectin that EVT encounter on invading the uterus increased HLA-G, EGF-Receptor-2, and LIF-Receptor expression on EVT, presumably representing a further differentiation state. Microarray and functional gene set enrichment analysis revealed a striking immune-activating potential for EVT that was absent in VT. Cocultures of HLA-G+ EVT with sample matched decidual natural killer cells (dNK), macrophages, and CD4+ and CD8+ T cells were established. Interaction of EVT with CD4+ T cells resulted in increased numbers of CD4+CD25(HI)FOXP3+CD45RA+ resting regulatory T cells (Treg) and increased the expression level of the Treg-specific transcription factor FOXP3 in these cells. However, EVT did not enhance cytokine secretion in dNK, whereas stimulation of dNK with mitogens or classical natural killer targets confirmed the distinct cytokine secretion profiles of dNK and peripheral blood NK cells (pNK). EVT are specialized cells involved in maternal-fetal tolerance, the properties of which are not imitated by HLA-G-expressing surrogate cell lines. PMID:26015573

  14. Gut hormones: emerging role in immune activation and inflammation.

    PubMed

    Khan, W I; Ghia, J E

    2010-07-01

    Gut inflammation is characterized by mucosal recruitment of activated cells from both the innate and adaptive immune systems. In addition to immune cells, inflammation in the gut is associated with an alteration in enteric endocrine cells and various biologically active compounds produced by these cells. Although the change in enteric endocrine cells or their products is considered to be important in regulating gut physiology (motility and secretion), it is not clear whether the change plays any role in immune activation and in the regulation of gut inflammation. Due to the strategic location of enteric endocrine cells in gut mucosa, these gut hormones may play an important role in immune activation and promotion of inflammation in the gut. This review addresses the research on the interface between immune and endocrine systems in gastrointestinal (GI) pathophysiology, specifically in the context of two major products of enteric endocrine systems, namely serotonin (5-hydroxytryptamine: 5-HT) and chromogranins (Cgs), in relation to immune activation and generation of inflammation. The studies reviewed in this paper demonstrate that 5-HT activates the immune cells to produce proinflammatory mediators and by manipulating the 5-HT system it is possible to modulate gut inflammation. In the case of Cgs the scenario is more complex, as this hormone has been shown to play both proinflammatory and anti-inflammatory functions. It is also possible that interaction between 5-HT and Cgs may play a role in the modulation of immune and inflammatory responses. In addition to enhancing our understanding of immunoendocrine interaction in the gut, the data generated from the these studies may have implications in understanding the role of gut hormone in the pathogenesis of both GI and non-GI inflammatory diseases which may lead ultimately to improved therapeutic strategies in inflammatory disorders. PMID:20408856

  15. Effect of maternal seaweed extract supplementation on suckling piglet growth, humoral immunity, selected microflora, and immune response after an ex vivo lipopolysaccharide challenge.

    PubMed

    Leonard, S G; Sweeney, T; Bahar, B; O'Doherty, J V

    2012-02-01

    The present study was conducted to investigate the effect of maternal dietary supplementation (n = 10 sows/treatment) with seaweed extract (SWE: 0 vs. 10.0 g/d) from d 107 of gestation until weaning (d 26) on neonatal piglet growth, humoral immunity, intestinal morphology, selected intestinal microflora, and VFA concentrations. Furthermore, this study examined the effect of dietary treatment on the immune response after an ex vivo Escherichia coli lipopolysaccharide (LPS) tissue challenge at weaning in a 2 × 2 factorial arrangement. The main factors consisted of sow dietary treatment (SWE or control) and immunological challenge (yes or no). The SWE supplement (10.0 g/d) contained laminarin (1.0 g), fucoidan (0.8 g), and ash (8.2 g) and was extracted from a Laminaria spp. The SWE-supplemented sows had greater colostrum IgA (P < 0.01) and had a trend for greater IgG (P = 0.062) concentrations compared with non-SWE-supplemented sows. Piglets suckling SWE-supplemented sows had greater serum IgG (P < 0.05) concentrations on d 14 of lactation compared with those suckling non-SWE-supplemented sows. Dietary SWE supplementation decreased fecal Enterobacteriaceae populations in sows at parturition (P < 0.05), and piglets suckling SWE-supplemented sows had a decreased colonic E. coli population at weaning (P < 0.01) compared with non-SWE-supplemented sows. Lipopolysaccharide challenge increased the mRNA abundances of the pro-inflammatory cytokines IL-1α and IL-6 (P < 0.01) in ileal tissue and tumor necrosis factor (TNF)-α in colonic (P < 0.01) tissue. There was a treatment × LPS challenge interaction for ileal TNF-α mRNA expression (P < 0.05). Piglets suckling SWE-supplemented sows had greater TNF-α mRNA expression after ex vivo LPS challenge compared with non-SWE-supplemented sows (P < 0.05). However, there was no effect of sow dietary treatment on TNF-α mRNA expression in the unchallenged ileal tissue. Piglet BW at birth and weaning, and small intestinal morphology

  16. Enhancing Cancer Immunotherapy Via Activation of Innate Immunity

    PubMed Central

    Goldberg, Jacob L.; Sondel, Paul M.

    2015-01-01

    Given recent technological advances and advances in our understanding of cancer, immunotherapy of cancer is being used with clear clinical benefit. The immunosuppression accompanying cancer itself, as well as with current cancer treatment with radiation or chemotherapy, impairs adaptive immune effectors to a greater extent than innate effector cells. In addition to being less suppressed, innate immune cells are capable of being enhanced via immune-stimulatory regimens. Most strategies being investigated to promote innate immune responses against cancer do not require complex, patient-specific, ex-vivo cellular or molecular creation of therapeutic agents; thus they can, generally, be used as “off the shelf” therapeutics that could be administered by most cancer clinics. Successful applications of innate immunotherapy in the clinic have effectively targeted components of the innate immune response. Preclinical data demonstrate how initiation of innate immune responses can lead to subsequent adaptive long-term cancer immunity. We hypothesize that integration of innate immune activation strategies into combination therapies for cancer treatment will lead to more effective and long term clinical benefit. PMID:26320061

  17. Effect of late-gestation maternal heat stress on growth and immune function of dairy calves.

    PubMed

    Tao, S; Monteiro, A P A; Thompson, I M; Hayen, M J; Dahl, G E

    2012-12-01

    Heat stress during the dry period affects the cow's mammary gland development, metabolism, and immunity during the transition period. However, the effect of late-gestation heat stress on calf performance and immune status is unknown. Our objective was to evaluate the effect of heat stress during the final ~45 d of gestation on growth and immune function of calves. Calves (17/treatment) were born to cows that were exposed to cooling (CL) or heat stress (HT) during the dry period. Only heifer calves (CL, n=12; HT, n=9) were used in measurements of growth and immune status after birth. Heifer calves were managed under identical conditions. All were fed 3.78 L of colostrum from their respective dams within 4 h of birth and were weaned at 2 mo of age (MOA). Body weight (BW) was obtained at weaning and then monthly until 7 MOA. Withers height (WH) was measured monthly from 3 to 7 MOA. Hematocrit and plasma total protein were assessed at birth, 1, 4, 7, 11, 14, 18, 21, 25, and 28 d of age. Total serum IgG was evaluated at 1, 4, 7, 11, 14, 18, 21, 25, and 28 d of age, and apparent efficiency of absorption was calculated. Peripheral blood mononuclear cells were isolated at 7, 28, 42, and 56 d of age, and proliferation rate was measured by (3)H-thymidine incorporation in vitro. Blood cortisol concentration was measured in the dams during the dry period and in calves in the preweaning period. Gestation length was 4d shorter for HT cows compared with CL cows. Calves from CL cows had greater BW than calves from HT cows at birth (42.5 vs. 36.5 kg). Compared with CL heifers, HT heifers had decreased weaning BW (78.5 vs. 65.9 kg) but similar BW (154.6 vs. 146.4 kg) and WH (104.8 vs. 103.4 cm) from 3 to 7 MOA. Compared with CL, heifers from HT cows had less total plasma protein (6.3 vs. 5.9 g/dL), total serum IgG (1,577.3 vs. 1,057.8 mg/dL), and apparent efficiency of absorption (33.6 vs. 19.2%), and tended to have decreased hematocrit (33 vs. 30%). Additionally, CL heifers had

  18. Modulation of macrophage activation and programming in immunity.

    PubMed

    Liu, Guangwei; Yang, Hui

    2013-03-01

    Macrophages are central mediators of the immune, contributing both to the initiation and the resolution of inflammation. The concept of macrophage activation and program has stimulated interest in its definition, and functional significance in homeostasis and diseases. It has been known that macrophages could be differently activated and programmed into different functional subtypes in response to different types of antigen stumuli or different kinds of cytokines present in the microenvironment and could thus profoundly influence immune responses, but little is known about the state and exact regulatory mechanism of macrophage activation and program from cell or molecular signaling level in immunity. In this review, we summarize the recent finding regarding the regulatory mechanism of macrophage activation and program toward M1 and M2, especially on M2 macrophages.

  19. Mucosal priming of newborn mice with S. Typhi Ty21a expressing anthrax protective antigen (PA) followed by parenteral PA-boost induces B and T cell-mediated immunity that protects against infection bypassing maternal antibodies

    PubMed Central

    Ramirez, Karina; Ditamo, Yanina; Galen, James E.; Baillie, Les W. J.; Pasetti, Marcela F.

    2010-01-01

    The currently licensed anthrax vaccine has several limitations and its efficacy has been proven only in adults. Effective immunization of newborns and infants requires adequate stimulation of their immune system, which is competent but not fully activated. We explored the use of the licensed live attenuated S. Typhi vaccine strain Ty21a expressing Bacillus anthracis protective antigen [Ty21a(PA)] followed PA-alum as a strategy for immunizing the pediatric population. Newborn mice primed with a single dose of Ty21a(PA) exhibited high frequencies of mucosal IgA-secreting B cells and IFN-γ-secreting T cells during the neonatal period, none of which was detected in newborns immunized with a single dose of PA-alum. Priming with Ty21a(PA) followed by PA-boost resulted in high levels of PA-specific IgG, toxin-neutralizing and opsonophagocytic antibodies and increased frequency of bone marrow IgG plasma cells and memory B cells compared with repeated immunization with PA-alum alone. Robust B and T cell responses developed even in the presence of maternal antibodies. The prime-boost protected against systemic and respiratory infection. Mucosal priming with a safe and effective S. Typhi-based anthrax vaccine followed by PA-boost could serve as a practical and effective prophylactic approach to prevent anthrax early in life. PMID:20619377

  20. Blocking IDO activity to enhance anti-tumor immunity.

    PubMed

    Munn, David H

    2012-01-01

    Tumors express potentially immunogenic antigens, yet the immune response to these antigens is typically profoundly suppressed. Patients with established tumors behave as if they were functionally tolerant to any antigens associated with the tumor. This tolerance reflects a process of active immune suppression elicited by the tumor, and represents a critical barrier to successful anti-tumor immunotherapy. Indoleamine 2,3-dioxygenase (IDO) is a natural immunoregulatory mechanism contributes to immune suppression and tolerance in a variety of settings. In tumor-bearing hosts, animal models suggest that tumor-induced IDO helps create a tolerogenic milieu within the tumor and the associated tumor-draining lymph nodes. IDO directly suppresses the proliferation and differentiation of effector T cells, and markedly enhances the suppressor activity of regulatory T cells (Tregs). Together, these effects contribute to the inability of the immune system to respond effectively to tumor antigens. Treatment of tumor-bearing animals with IDO-inhibitor drugs enhances anti-tumor immune responses, and IDO-inhibitors are synergistic with a variety of chemotherapeutic drugs, anti-tumor vaccines and other immunotherapy. Strategies to pharmacologically inhibit IDO may thus enhance immune-mediated responses following conventional chemotherapy, and may be synergistic with other forms of immunotherapy.

  1. Effect of hen age and maternal vitamin D source on performance, hatchability, bone mineral density, and progeny in vitro early innate immune function.

    PubMed

    Saunders-Blades, J L; Korver, D R

    2015-06-01

    The metabolite 25-hydroxy vitamin D3 (25-OHD) can complement or replace vitamin D3 in poultry rations, and may influence broiler production and immune function traits. The effect of broiler breeder dietary 25-OHD on egg production, hatchability, and chick early innate immune function was studied. We hypothesized that maternal dietary 25-OHD would support normal broiler breeder production and a more mature innate immune system of young chicks. Twenty-three-week-old Ross 308 hens (n=98) were placed in 4 floor pens and fed either 2,760 IU vitamin D3 (D) or 69 μg 25-OHD/kg feed. Hen weights were managed according to the primary breeder management guide. At 29 to 31 wk (Early), 46 to 48 wk (Mid), and 61 to 63 wk (Late), hens were artificially inseminated and fertile eggs incubated and hatched. Chicks were placed in cages based on maternal treatment and grown to 7 d age. Innate immune function and plasma 25-OHD were assessed at 1 and 4 d post-hatch on 15 chicks/treatment. Egg production, hen BW, and chick hatch weight were not affected by diet (P>0.05). Total in vitro Escherichia coli (E. coli) killing by 25-OHD chicks was greater than the D chicks at 4 d for the Early and Mid hatches, and 1 and 4 d for the Late hatch. This can be partly explained by the 25-OHD chicks from the Late hatch also having a greater E. coli phagocytic capability. No consistent pattern of oxidative burst response was observed. Chicks from the Mid hatch had greater percent phagocytosis, phagocytic capability, and E. coli killing than chicks from Early and Late hatches. Overall, maternal 25-OHD increased hatchability and in vitro chick innate immunity towards E. coli. Regardless of treatment, chicks from Late and Early hens had weaker early innate immune responses than chicks from Mid hens. The hen age effect tended to be the greatest factor influencing early chick innate immunity, but maternal 25-OHD also increased several measures relative to D.

  2. Maternal country of origin, breast milk characteristics and potential influences on immunity in offspring.

    PubMed

    Holmlund, U; Amoudruz, P; Johansson, M A; Haileselassie, Y; Ongoiba, A; Kayentao, K; Traoré, B; Doumbo, S; Schollin, J; Doumbo, O; Montgomery, S M; Sverremark-Ekström, E

    2010-12-01

    Breast milk contains pro- and anti-inflammatory cytokines and chemokines with potential to influence immunological maturation in the child. We have shown previously that country of birth is associated with the cytokine/chemokine profile of breast milk. In this study we have investigated how these differences in breast milk affect the cellular response of cord blood mononuclear cells (CBMCs) and intestinal epithelial cells (IECs, cell line HT-29) to microbial challenge. Ninety-five women were included: 30 from Mali in West Africa, 32 Swedish immigrants and 33 native Swedish women. CBMCs or IECs were stimulated in vitro with breast milk, alone or in combination with lipopolysaccharide (LPS) or peptidoglycan (PGN). Breast milk in general abrogated the LPS-induced down-regulation of surface CD14 and Toll-like receptor (TLR)-4 expression on CB monocytes, while inhibiting the PGN-induced TLR-2 up-regulation. However, breast milk from immigrant women together with LPS induced a lower CBMC release of interleukin (IL)-6 (P = 0·034) and CXCL-8/IL-8 (P = 0·037) compared with breast milk from Swedish women, while breast milk from Swedish women and Mali women tended to increase the response. The same pattern of CXCL-8/IL-8 release could be seen after stimulation of IECs (HT-29). The lower CBMC and IEC (HT-29) responses to microbial compounds by breast milk from immigrant women could be explained by the fact that breast milk from the immigrant group showed a divergent pro- and anti-inflammatory content for CXCL-8/IL-8, transforming growth factor-β1 and soluble CD14, compared to the other two groups of women. This may have implications for maturation of their children's immune responses. PMID:20942805

  3. Maternal immunization in Argentina: A storyline from the prospective of a middle income country.

    PubMed

    Vizzotti, C; Neyro, S; Katz, N; Juárez, M V; Perez Carrega, M E; Aquino, A; Kaski Fullone, F

    2015-11-25

    The importance of vaccination during pregnancy lies not only in directly protecting vaccinated women, but also by indirectly protecting small infants during the first few months of life. Vaccination against the flu and whooping cough is a priority within the comprehensive care strategy for pregnant women and small infants in Argentina, in the context of transitioning from child vaccination to family vaccination. In 2011, the flu vaccine was included in the National Immunization Schedule (NIS) as mandatory and free of charge, with the aim of decreasing complications and death due to influenza in the at-risk population in Argentina. The national vaccination coverage attained in pregnant women in the past 4 years (2011-2014) has been satisfactory; 88% coverage was attained in the year this program was introduced to the schedule. In the following years, coverage was maintained at greater than 95%. In February 2012, Argentina became the first country in Latin America to have universal vaccination strategy for pregnant women against whooping cough. This recommendation was implemented throughout the country by vaccination with the diphtheria toxoid, tetanus toxoid, and acellular pertussis (Tdap) vaccine starting at 20 weeks of pregnancy, with the aim of decreasing morbimortality due to whooping cough in infants under 6 months of age. The vaccine was incorporated into the NIS in 2014. More than 1,200,000 doses were applied in this period. Both vaccines showed a suitable safety profile and no serious events were reported. Argentina is an example of a middle-income country that has been able to implement a successful strategy for primary prevention through vaccines, making it a health policy.

  4. Maternal immunization in Argentina: A storyline from the prospective of a middle income country.

    PubMed

    Vizzotti, C; Neyro, S; Katz, N; Juárez, M V; Perez Carrega, M E; Aquino, A; Kaski Fullone, F

    2015-11-25

    The importance of vaccination during pregnancy lies not only in directly protecting vaccinated women, but also by indirectly protecting small infants during the first few months of life. Vaccination against the flu and whooping cough is a priority within the comprehensive care strategy for pregnant women and small infants in Argentina, in the context of transitioning from child vaccination to family vaccination. In 2011, the flu vaccine was included in the National Immunization Schedule (NIS) as mandatory and free of charge, with the aim of decreasing complications and death due to influenza in the at-risk population in Argentina. The national vaccination coverage attained in pregnant women in the past 4 years (2011-2014) has been satisfactory; 88% coverage was attained in the year this program was introduced to the schedule. In the following years, coverage was maintained at greater than 95%. In February 2012, Argentina became the first country in Latin America to have universal vaccination strategy for pregnant women against whooping cough. This recommendation was implemented throughout the country by vaccination with the diphtheria toxoid, tetanus toxoid, and acellular pertussis (Tdap) vaccine starting at 20 weeks of pregnancy, with the aim of decreasing morbimortality due to whooping cough in infants under 6 months of age. The vaccine was incorporated into the NIS in 2014. More than 1,200,000 doses were applied in this period. Both vaccines showed a suitable safety profile and no serious events were reported. Argentina is an example of a middle-income country that has been able to implement a successful strategy for primary prevention through vaccines, making it a health policy. PMID:26277071

  5. Multifunctional antimicrobial proteins and peptides: natural activators of immune systems.

    PubMed

    Niyonsaba, François; Nagaoka, Isao; Ogawa, Hideoki; Okumura, Ko

    2009-01-01

    In addition to the physical barrier of the stratum corneum, cutaneous innate immunity also includes the release of various humoral mediators, such as cytokines and chemokines, recruitment and activation of phagocytes, and the production of antimicrobial proteins/peptides (AMPs). AMPs form an innate epithelial chemical shield, which provides a front-line component in innate immunity to inhibit microbial invasion; however, this might be an oversimplification of the diverse functions of these molecules. In fact, apart from exhibiting a broad spectrum of microbicidal properties, it is increasingly evident that AMPs display additional activities that are related to the stimulation and modulation of the cutaneous immune system. These diverse functions include chemoattraction and activation of immune and/or inflammatory cells, the production and release of cytokines and chemokines, acceleration of angiogenesis, promotion of wound healing, neutralization of harmful microbial products, and bridging of both innate and adaptive immunity. Thus, better understanding of the functions of AMPs in skin and identification of their signaling mechanisms may offer new strategies for the development of potential therapeutics for the treatment of infection- and/or inflammation-related skin diseases. Here, we briefly outline the structure, regulation of expression, and multifunctional roles of principal skin-derived AMPs.

  6. Immunosuppressive activity of tilmicosin on the immune responses in mice.

    PubMed

    Guan, Shuang; Song, Yu; Guo, Weixiao; Chu, Xiao; Zhang, Xiaozhe; Wang, Dacheng; Lu, Jing; Deng, Xuming

    2011-06-01

    Tilmicosin, a semi-synthetic macrolide antibiotic that is only used in the veterinary clinic, was evaluated for its immunosuppressive activity on the immune responses to ovalbumin (OVA) in mice. Tilmicosin suppressed concanavalin A (Con A)- and lipopolysaccharide (LPS)-stimulated splenocyte proliferation in vitro. BALB/c mice were immunized subcutaneously with OVA on day 1 and 4. Beginning on the day of boosting immunization, the mice were administered intraperitoneally with tilmicosin at a single dose of 10, 30, and 90 mg/kg for 10 consecutive days. On day 14, blood samples were collected for measuring specific total-immunoglobulin G (total-IgG), IgG1, IgG2b, and splenocytes were harvested for determining lymphocyte proliferation and interleukin-2 (IL-2), interferon-γ (IFN-γ), IL-4 production. The results demonstrated that tilmicosin could significantly suppress Con A-induced splenocyte proliferation in a dose-dependent manner, decrease LPS-and OVA-induced splenocyte proliferation only at high concentration, produced less IL-2, IL-4, and IFN-γ as compared to the control in the OVA-immunized mice. Moreover, the OVA-specific IgG, IgG1, and IgG2b levels in the OVA-immunized mice were reduced by tilmicosin. These results suggest that tilmicosin could suppress the cellular and humoral immune response in mice.

  7. Epidemic spreading and immunization in node-activity networks

    NASA Astrophysics Data System (ADS)

    Wu, Qingchu; Chen, Shufang

    2015-09-01

    In this paper, we study the epidemic spreading in node-activity networks, where an individual participates in social networks with a certain rate h. There are two cases for h: the state-independent case and the state-dependent case. We investigate the epidemic threshold as a function of h compared to the static network. Our results suggest the epidemic threshold cannot be exactly predicted by using the analysis approach in the static network. In addition, we further propose a local information-based immunization protocol on node-activity networks. Simulation analysis shows that the immunization can not only eliminate the infectious disease, but also change the epidemic threshold via increasing the immunization parameter.

  8. An active immunization approach to generate protective catalytic antibodies.

    PubMed Central

    Wang, J; Han, Y; Wilkinson, M F

    2001-01-01

    We report that mice immunized with a phosphate immunogen produced polyclonal catalytic antibodies (PCAbs) that catalysed the hydrolysis of carbaryl, a widely used broad-spectrum carbamate insecticide that exerts toxic effects in animals and humans. The reaction catalysed by the PCAbs (IgGs) obeyed Michaelis-Menten kinetics in vitro with the following values at pH 8.0 and 25 degrees C: K(m) approximately 8.0 microM, k(cat)=4.8x10(-3)-5.8x10(-1), k(cat)/k(non-cat)=5.6x10(1)-6.8x10(3) (where k(non-cat) is the rate constant of the reaction in the absence of added catalyst). The PCAbs were also active in whole sera under physiological conditions in vitro. The PCAbs induced in vivo were also active in vivo, as immunization with the phosphate immunogen decreased the mouse blood concentration of carbaryl. To our knowledge, this is the first report demonstrating that active immunization generates antibodies possessing therapeutic catalytic function in vivo. We propose that active immunization schemes that induce enzymically active antibodies may provide a highly specific therapeutic approach for degrading toxic substances. PMID:11696002

  9. Pathogen-Secreted Proteases Activate a Novel Plant Immune Pathway

    PubMed Central

    Cheng, Zhenyu; Li, Jian-Feng; Niu, Yajie; Zhang, Xue-Cheng; Woody, Owen Z.; Xiong, Yan; Djonović, Slavica; Millet, Yves; Bush, Jenifer; McConkey, Brendan J.; Sheen, Jen; Ausubel, Frederick M.

    2015-01-01

    Mitogen-Activated Protein Kinase (MAPK) cascades play central roles in innate immune signaling networks in plants and animals1,2. In plants, however, the molecular mechanisms of how signal perception is transduced to MAPK activation remain elusive1. We report that pathogen-secreted proteases activate a previously unknown signaling pathway in Arabidopsis thaliana involving the Gα, Gβ and Gγ subunits of heterotrimeric G-protein complexes, which function upstream of a MAPK cascade. In this pathway, Receptor for Activated C Kinase 1 (RACK1) functions as a novel scaffold that binds to the Gβ subunit as well as to all three tiers of the MAPK cascade, thereby linking upstream G protein signaling to downstream activation of a MAPK cascade. The protease-G protein-RACK1-MAPK cascade modules identified in these studies are distinct from previously described plant immune signaling pathways such as the one elicited by bacterial flagellin, in which G proteins function downstream of or in parallel to a MAPK cascade without the involvement of the RACK1 scaffolding protein. The discovery of the novel protease-mediated immune signaling pathway described here was facilitated by the use of the broad host range, opportunistic bacterial pathogen Pseudomonas aeruginosa. The ability of P. aeruginosa to infect both plants and animals makes it an excellent model to identify novel types of immunoregulatory strategies that account for its niche adaptation to diverse host tissues and immune systems. PMID:25731164

  10. Immunization

    MedlinePlus

    ... a lot worse. Some are even life-threatening. Immunization shots, or vaccinations, are essential. They protect against things like measles, ... B, polio, tetanus, diphtheria, and pertussis (whooping cough). Immunizations are important for adults as well as children. ...

  11. Immunizations

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Immunizations KidsHealth > For Teens > Immunizations Print A A A ... That Shot? en español Las vacunas Why Are Vaccinations Important? Measles, mumps, and whooping cough may seem ...

  12. Maternal inflammation during late pregnancy is lower in physically active compared to inactive obese women

    PubMed Central

    Tinius, Rachel A.; Cahill, Alison G.; Strand, Eric A.; Todd Cade, W.

    2016-01-01

    Purpose The primary purpose of this study was to compare maternal plasma inflammation between physically active and inactive obese women during late pregnancy. The secondary purpose was to examine the relationships between maternal plasma inflammation and lipid metabolism and maternal and neonatal metabolic health in these women. Methods A cross-sectional, observational study design was performed in 16 obese-inactive ((OBI) age: 25.0 ± 4.8 years, pre-pregnancy BMI: 36.3 ± 4.3kg/m2, body fat percentage in late gestation: 37.7 ± 3.5%) and 16 obese-active ((OBA) age: 28.9 ± 4.8 years, pre-pregnancy BMI: 34.0±3.7kg/m2, body fat in late gestation: 36.6 ± 3.8%) women during the third trimester of pregnancy. Maternal plasma inflammation (C -reactive protein (CRP)) and insulin resistance (Homeostatic Model Assessment-Insulin Resistance (HOMA-IR)) were measured at rest. Plasma lipid concentration and metabolism (lipid oxidation and lipolysis) were measured at rest, during a 30-minute bout of low-intensity (40% VO2peak) exercise, and during a resting recovery period using indirect calorimetry. Umbilical cord blood was collected for measurement of neonatal plasma insulin resistance, inflammation, and lipid concentration. Neonatal body composition was measured via air displacement plethysmography. Results Maternal plasma CRP concentration was significantly higher in OBI compared to OBA women (9.1 ± 4.0 mg/L versus 6.3 ±2.5mg/L, p=0.02). Maternal plasma CRP concentration was significantly associated with maternal lipolysis (r=0.43, p=0.02), baseline lipid oxidation rate (r=0.39, p=0.03), and baseline plasma free fatty acid concentration (r=0.36, p=0.04). Conclusions Maternal physical activity may reduce inflammation during pregnancy in obese women. Maternal lipid metabolism is related to systemic inflammation. PMID:26799789

  13. Immune-Checkpoint Blockade and Active Immunotherapy for Glioma

    PubMed Central

    Ahn, Brian J.; Pollack, Ian F.; Okada, Hideho

    2013-01-01

    Cancer immunotherapy has made tremendous progress, including promising results in patients with malignant gliomas. Nonetheless, the immunological microenvironment of the brain and tumors arising therein is still believed to be suboptimal for sufficient antitumor immune responses for a variety of reasons, including the operation of “immune-checkpoint” mechanisms. While these mechanisms prevent autoimmunity in physiological conditions, malignant tumors, including brain tumors, actively employ these mechanisms to evade from immunological attacks. Development of agents designed to unblock these checkpoint steps is currently one of the most active areas of cancer research. In this review, we summarize recent progresses in the field of brain tumor immunology with particular foci in the area of immune-checkpoint mechanisms and development of active immunotherapy strategies. In the last decade, a number of specific monoclonal antibodies designed to block immune-checkpoint mechanisms have been developed and show efficacy in other cancers, such as melanoma. On the other hand, active immunotherapy approaches, such as vaccines, have shown encouraging outcomes. We believe that development of effective immunotherapy approaches should ultimately integrate those checkpoint-blockade agents to enhance the efficacy of therapeutic approaches. With these agents available, it is going to be quite an exciting time in the field. The eventual success of immunotherapies for brain tumors will be dependent upon not only an in-depth understanding of immunology behind the brain and brain tumors, but also collaboration and teamwork for the development of novel trials that address multiple layers of immunological challenges in gliomas. PMID:24202450

  14. [Enhancing antibodies and supressive cells in maternal anti-fetal immune reaction].

    PubMed

    Chaouat, G; Voisin, G A; Daëron, M; Kanellopoulos, J

    1977-01-01

    Some of the mechanisms of tolerance to the foetal allograft have been studied in vivo, both at cellular and humoral level. It has been shown that immunoglobulins, mostly IgG1, can be detected and eluted from the placenta of allogeneic and syngeneic pregnancies in a wide variety of combination (CBA, C57Ks A/Jax, Balb C, DBA2). These immunoglobulins, in the case of allogeneic pregnancy, bind to paternal thymocytes exclusively, demonstrating antibody activity toward paternal antigens. They promote (although partly "non-specifically") direct allogeneic mast cell degranulation. In vivo, eluates only from a C57Ks female X A/Jax male placenta exclusively induce a significant enhancement of SA1 (A/Jax, h-2a strain) tumor graft in C57Ks (H-2d) recipients. Intraperitoneal transfer of 1.0 to 1.7 X 10(7) spleen cells from C57Ks two weeks pregnant from A/Jax male does also promotes SA1 growth and survival. T and B enriched population, obtained by the nylon wool techniques, display similar activity. Further experiments are in progress to discard T cell contamination in the B enriched population and to study eventual macrophage involvement. Thus, two agents of the facilitation reaction--suppressor cells and enhancing antibodies--have been demonstrated in vivo during pregnacy, protecting the foetus against hazards of the rejection reaction, which is also demonstrates by other in vivo techniques in our laboratory.

  15. Photodynamic therapy for cancer and activation of immune response

    NASA Astrophysics Data System (ADS)

    Mroz, Pawel; Huang, Ying-Ying; Hamblin, Michael R.

    2010-02-01

    Anti-tumor immunity is stimulated after PDT for cancer due to the acute inflammatory response, exposure and presentation of tumor-specific antigens, and induction of heat-shock proteins and other danger signals. Nevertheless effective, powerful tumor-specific immune response in both animal models and also in patients treated with PDT for cancer, is the exception rather than the rule. Research in our laboratory and also in others is geared towards identifying reasons for this sub-optimal immune response and discovering ways of maximizing it. Reasons why the immune response after PDT is less than optimal include the fact that tumor-antigens are considered to be self-like and poorly immunogenic, the tumor-mediated induction of CD4+CD25+foxP3+ regulatory T-cells (T-regs), that are able to inhibit both the priming and the effector phases of the cytotoxic CD8 T-cell anti-tumor response and the defects in dendritic cell maturation, activation and antigen-presentation that may also occur. Alternatively-activated macrophages (M2) have also been implicated. Strategies to overcome these immune escape mechanisms employed by different tumors include combination regimens using PDT and immunostimulating treatments such as products obtained from pathogenic microorganisms against which mammals have evolved recognition systems such as PAMPs and toll-like receptors (TLR). This paper will cover the use of CpG oligonucleotides (a TLR9 agonist found in bacterial DNA) to reverse dendritic cell dysfunction and methods to remove the immune suppressor effects of T-regs that are under active study.

  16. Seasonality in maternal intake and activity influence offspring’s birth size among rural Indian mothers—Pune Maternal Nutrition Study

    PubMed Central

    Rao, Shobha; Kanade, Asawari N; Yajnik, Chittaranjan S; Fall, Caroline H D

    2012-01-01

    Background Farming populations from developing countries are exposed to seasonal energy stress due to variations in food availability and energy output related to agricultural activities. This study aims to examine the impact of seasonality in maternal intake and activity on neonatal size. Methods Maternal anthropometry, dietary intakes (24-h recall and food-frequency questionnaire) and activity pattern (questionnaire) at 18±2 and 28±2 weeks gestation, and neonatal anthropometry, were measured in a prospective study of 797 rural Indian women. Results Maternal energy and protein intakes were inadequate (70% of recommended dietary allowance). Both intake and activity showed seasonal variation (P=0.001), with peak values in winter i.e. during harvest, at 18 weeks (median energy 1863 kcal/day, protein 47.5 g/day) and 28 weeks (median energy 1687 kcal/day, protein 43.7 g/day), coinciding with the maximum maternal activity (median score 86.1 at 18 weeks and 79.5 at 28 weeks). Mean birth weight and length (adjusted for pre-pregnant weight, parity, gestation and sex) of babies was highest in summer (peak at February 2733 g, 48.6 cm, respectively) and lowest in winter (nadir at January 2591 g, 47.1 cm, respectively). Regression analysis showed that maternal intake at 18th week had a positive association (P=0.05), maternal activity at 28th week had a negative association (P=0.002) and exposure (in weeks) to winter during gestation had a positive association (P=0.04) with birth size. Furthermore, higher maternal intakes, coupled with lower maternal activity in late gestation were associated with higher birth weight, especially during winter. Conclusions If causal, these observations indicate that complete exposure (16 weeks) to the winter season (harvest-time) in late gestation could increase birth weight by 90 g in poor farming communities in rural India, and the benefit would increase further by lowering maternal activity. Our results underscore the importance of

  17. Measuring MAP kinase activity in immune complex assays.

    PubMed

    Cherkasova, Vera A

    2006-11-01

    I present an overview of published methods for measuring mitogen activated protein (MAP) kinase activity on endogenous associated substrates, exogenously added substrates as well as determination of activation loop phosphorylation as a read-out of kinase activity in vivo. Detailed procedures for these assays are given for two MAP kinases (MAPKs) Fus3 and Kss1 and compared with other published protocols, including the protocols for Hog1 and Mpk1 MAPKs. Measuring kinase activity in immune complex assays can serve as an approach for identification of potential substrates of protein kinases as well as for detecting other kinase-associated proteins. PMID:16890454

  18. Right Frontoinsular Cortex and Subcortical Activity to Infant Cry Is Associated with Maternal Mental State Talk

    PubMed Central

    Phillips, Mary L.; Swain, James E.; Moses-Kolko, Eydie L.

    2015-01-01

    The study objective was to examine neural correlates of a specific component of human caregiving: maternal mental state talk, reflecting a mother's proclivity to attribute mental states and intentionality to her infant. Using a potent, ecologically relevant stimulus of infant cry during fMRI, we tested hypotheses that postpartum neural response to the cry of “own” versus a standard “other” infant in the right frontoinsular cortex (RFIC) and subcortical limbic network would be associated with independent observations of maternal mental state talk. The sample comprised 76 urban-living, low socioeconomic mothers (82% African American) and their 4-month-old infants. Before the fMRI scan, mothers were filmed in face-to-face interaction with their infant, and maternal behaviors were coded by trained researchers unaware of all other information about the participants. The results showed higher functional activity in the RFIC to own versus other infant cry at the group level. In addition, RFIC and bilateral subcortical neural activity (e.g., thalamus, amygdala, hippocampus, putamen) was associated positively with maternal mental state talk but not with more global aspects of observed caregiving. These findings held when accounting for perceptual and contextual covariates, such as maternal felt distress, urge to help, depression severity, and recognition of own infant cry. Our results highlight the need to focus on specific components of caregiving to advance understanding of the maternal brain. Future work will examine the predictive utility of this neural marker for mother–child function. SIGNIFICANCE STATEMENT The current study advances extant literature examining the neural underpinning of early parenting behavior. The findings highlight the special functional importance of the right frontoinsular cortex–thalamic–limbic network in a mother's proclivity to engage in mental state talk with her preverbal infant, a circumscribed aspect of maternal caregiving

  19. Chicken Immune Response after In Ovo Immunization with Chimeric TLR5 Activating Flagellin of Campylobacter jejuni

    PubMed Central

    Radomska, Katarzyna A.; Vaezirad, Mahdi M.; Verstappen, Koen M.; Wösten, Marc M. S. M.; Wagenaar, Jaap A.; van Putten, Jos P. M.

    2016-01-01

    Campylobacter jejuni is the main cause of bacterial food-borne diseases in developed countries. Chickens are the most important source of human infection. Vaccination of poultry is an attractive strategy to reduce the number of C. jejuni in the intestinal tract of chickens. We investigated the immunogenicity and protective efficacy of a recombinant C. jejuni flagellin-based subunit vaccine with intrinsic adjuvant activity. Toll-like receptor activation assays demonstrated the purity and TLR5 stimulating (adjuvant) activity of the vaccine. The antigen (20–40 μg) was administered in ovo to 18 day-old chicken embryos. Serum samples and intestinal content were assessed for antigen-specific systemic and mucosal humoral immune responses. In ovo vaccination resulted in the successful generation of IgY and IgM serum antibodies against the flagellin-based subunit vaccine as determined by ELISA and Western blotting. Vaccination did not induce significant amounts of flagellin-specific secretory IgA in the chicken intestine. Challenge of chickens with C. jejuni yielded similar intestinal colonization levels for vaccinated and control animals. Our results indicate that in ovo delivery of recombinant C. jejuni flagellin subunit vaccine is a feasible approach to yield a systemic humoral immune response in chickens but that a mucosal immune response may be needed to reduce C. jejuni colonization. PMID:27760175

  20. Lymphatic system: an active pathway for immune protection.

    PubMed

    Liao, Shan; von der Weid, P Y

    2015-02-01

    Lymphatic vessels are well known to participate in the immune response by providing the structural and functional support for the delivery of antigens and antigen presenting cells to draining lymph nodes. Recent advances have improved our understanding of how the lymphatic system works and how it participates to the development of immune responses. New findings suggest that the lymphatic system may control the ultimate immune response through a number of ways which may include guiding antigen/dendritic cells (DC) entry into initial lymphatics at the periphery; promoting antigen/DC trafficking through afferent lymphatic vessels by actively facilitating lymph and cell movement; enabling antigen presentation in lymph nodes via a network of lymphatic endothelial cells and lymph node stroma cell and finally by direct lymphocytes exit from lymph nodes. The same mechanisms are likely also important to maintain peripheral tolerance. In this review we will discuss how the morphology and gene expression profile of the lymphatic endothelial cells in lymphatic vessels and lymph nodes provides a highly efficient pathway to initiate immune responses. The fundamental understanding of how lymphatic system participates in immune regulation will guide the research on lymphatic function in various diseases.

  1. The uses and results of active tetanus immunization

    PubMed Central

    Scheibel, Inga

    1955-01-01

    Both in animal experiments and in the course of two world wars active immunization has proved a safe method of protection against tetanus, and a method superior to passive serum prophylaxis. The three types of vaccine—plain, combined, and precipitated or adsorbed—all have their advantages and disadvantages, and the choice between them must be left to individual national health authorities. They should, however, be administered in two or three doses to confer basic immunity. What amount of circulating antitoxin is necessary to give full protection has not been accurately determined, but it is clear that one recall dose should be given about a year after the first injections as part of the routine course of injections. This seems enough to provide a long-lasting immunity, but a dose of vaccine should also be given at the time of injury. General immunization of the population is not practicable, but children, who are among the groups most at risk, can be immunized relatively simply by combined diphtheria and tetanus vaccine; in many countries, indeed, this is being done on an ever-increasing scale. PMID:13270078

  2. Frequency of Maternal Touch Predicts Resting Activity and Connectivity of the Developing Social Brain

    PubMed Central

    Brauer, Jens; Xiao, Yaqiong; Poulain, Tanja; Friederici, Angela D.; Schirmer, Annett

    2016-01-01

    Previous behavioral research points to a positive relationship between maternal touch and early social development. Here, we explored the brain correlates of this relationship. The frequency of maternal touch was recorded for 43 five-year-old children during a 10 min standardized play session. Additionally, all children completed a resting-state functional magnetic resonance imaging session. Investigating the default mode network revealed a positive relation between the frequency of maternal touch and activity in the right posterior superior temporal sulcus (pSTS) extending into the temporo-parietal junction. Using this effect as a seed in a functional connectivity analysis identified a network including extended bilateral regions along the temporal lobe, bilateral frontal cortex, and left insula. Compared with children with low maternal touch, children with high maternal touch showed additional connectivity with the right dorso-medial prefrontal cortex. Together these results support the notion that childhood tactile experiences shape the developing “social brain” with a particular emphasis on a network involved in mentalizing. PMID:27230216

  3. Frequency of Maternal Touch Predicts Resting Activity and Connectivity of the Developing Social Brain.

    PubMed

    Brauer, Jens; Xiao, Yaqiong; Poulain, Tanja; Friederici, Angela D; Schirmer, Annett

    2016-08-01

    Previous behavioral research points to a positive relationship between maternal touch and early social development. Here, we explored the brain correlates of this relationship. The frequency of maternal touch was recorded for 43 five-year-old children during a 10 min standardized play session. Additionally, all children completed a resting-state functional magnetic resonance imaging session. Investigating the default mode network revealed a positive relation between the frequency of maternal touch and activity in the right posterior superior temporal sulcus (pSTS) extending into the temporo-parietal junction. Using this effect as a seed in a functional connectivity analysis identified a network including extended bilateral regions along the temporal lobe, bilateral frontal cortex, and left insula. Compared with children with low maternal touch, children with high maternal touch showed additional connectivity with the right dorso-medial prefrontal cortex. Together these results support the notion that childhood tactile experiences shape the developing "social brain" with a particular emphasis on a network involved in mentalizing.

  4. Frequency of Maternal Touch Predicts Resting Activity and Connectivity of the Developing Social Brain.

    PubMed

    Brauer, Jens; Xiao, Yaqiong; Poulain, Tanja; Friederici, Angela D; Schirmer, Annett

    2016-08-01

    Previous behavioral research points to a positive relationship between maternal touch and early social development. Here, we explored the brain correlates of this relationship. The frequency of maternal touch was recorded for 43 five-year-old children during a 10 min standardized play session. Additionally, all children completed a resting-state functional magnetic resonance imaging session. Investigating the default mode network revealed a positive relation between the frequency of maternal touch and activity in the right posterior superior temporal sulcus (pSTS) extending into the temporo-parietal junction. Using this effect as a seed in a functional connectivity analysis identified a network including extended bilateral regions along the temporal lobe, bilateral frontal cortex, and left insula. Compared with children with low maternal touch, children with high maternal touch showed additional connectivity with the right dorso-medial prefrontal cortex. Together these results support the notion that childhood tactile experiences shape the developing "social brain" with a particular emphasis on a network involved in mentalizing. PMID:27230216

  5. Immune Activation Reduces Sperm Quality in the Great Tit

    PubMed Central

    Losdat, Sylvain; Richner, Heinz; Blount, Jonathan D.; Helfenstein, Fabrice

    2011-01-01

    Mounting an immune response against pathogens incurs costs to organisms by its effects on important life-history traits, such as reproductive investment and survival. As shown recently, immune activation produces large amounts of reactive species and is suggested to induce oxidative stress. Sperm are highly susceptible to oxidative stress, which can negatively impact sperm function and ultimately male fertilizing efficiency. Here we address the question as to whether mounting an immune response affects sperm quality through the damaging effects of oxidative stress. It has been demonstrated recently in birds that carotenoid-based ornaments can be reliable signals of a male's ability to protect sperm from oxidative damage. In a full-factorial design, we immune-challenged great tit males while simultaneously increasing their vitamin E availability, and assessed the effect on sperm quality and oxidative damage. We conducted this experiment in a natural population and tested the males' response to the experimental treatment in relation to their carotenoid-based breast coloration, a condition-dependent trait. Immune activation induced a steeper decline in sperm swimming velocity, thus highlighting the potential costs of an induced immune response on sperm competitive ability and fertilizing efficiency. We found sperm oxidative damage to be negatively correlated with sperm swimming velocity. However, blood resistance to a free-radical attack (a measure of somatic antioxidant capacity) as well as plasma and sperm levels of oxidative damage (lipid peroxidation) remained unaffected, thus suggesting that the observed effect did not arise through oxidative stress. Towards the end of their breeding cycle, swimming velocity of sperm of more intensely colored males was higher, which has important implications for the evolution of mate choice and multiple mating in females because females may accrue both direct and indirect benefits by mating with males having better quality sperm

  6. Biophysical Aspects of T Lymphocyte Activation at the Immune Synapse

    PubMed Central

    Hivroz, Claire; Saitakis, Michael

    2016-01-01

    T lymphocyte activation is a pivotal step of the adaptive immune response. It requires the recognition by T-cell receptors (TCR) of peptides presented in the context of major histocompatibility complex molecules (pMHC) present at the surface of antigen-presenting cells (APCs). T lymphocyte activation also involves engagement of costimulatory receptors and adhesion molecules recognizing ligands on the APC. Integration of these different signals requires the formation of a specialized dynamic structure: the immune synapse. While the biochemical and molecular aspects of this cell–cell communication have been extensively studied, its mechanical features have only recently been addressed. Yet, the immune synapse is also the place of exchange of mechanical signals. Receptors engaged on the T lymphocyte surface are submitted to many tensile and traction forces. These forces are generated by various phenomena: membrane undulation/protrusion/retraction, cell mobility or spreading, and dynamic remodeling of the actomyosin cytoskeleton inside the T lymphocyte. Moreover, the TCR can both induce force development, following triggering, and sense and convert forces into biochemical signals, as a bona fide mechanotransducer. Other costimulatory molecules, such as LFA-1, engaged during immune synapse formation, also display these features. Moreover, T lymphocytes themselves are mechanosensitive, since substrate stiffness can modulate their response. In this review, we will summarize recent studies from a biophysical perspective to explain how mechanical cues can affect T lymphocyte activation. We will particularly discuss how forces are generated during immune synapse formation; how these forces affect various aspects of T lymphocyte biology; and what are the key features of T lymphocyte response to stiffness. PMID:26913033

  7. Maternal high-fat diet acts as a stressor increasing maternal glucocorticoids' signaling to the fetus and disrupting maternal behavior and brain activation in C57BL/6J mice.

    PubMed

    Bellisario, Veronica; Panetta, Pamela; Balsevich, Georgia; Baumann, Valentin; Noble, June; Raggi, Carla; Nathan, Olivia; Berry, Alessandra; Seckl, Jonathan; Schmidt, Mathias; Holmes, Megan; Cirulli, Francesca

    2015-10-01

    Maternal diet during pregnancy can impact maternal behavior as well as the intrauterine environment, playing a critical role in programming offspring's physiology. In a preliminary study, we found a strong association between high-fat diet (HFD) during pregnancy and increased cannibalistic episodes and dams' mortality during late pregnancy and parturition. Based upon these data, we hypothesized that HFD during pregnancy could negatively affect neuroendocrine and metabolic regulations occurring during the final stages of pregnancy, thereby disrupting maternal behavior. To test this hypothesis, female C57BL/6J mice were fed HFD or control diet for 11 weeks until three days before the expected delivery date. Basal corticosterone plasma levels and brain levels of c-Fos were measured both before and after delivery, in addition to leptin levels in the adipose tissue. Dam's emotional behavior and social anxiety, in addition to locomotor activity were assessed before parturition. Data show that HFD led to aberrant maternal behavior, dams being characterized by behaviors related to aggression toward an unfamiliar social stimulus in the social avoidance test, in addition to decreased locomotor activity. Neural activity in HFD dams was reduced in the olfactory bulbs, a crucial brain region for social and olfactory recognition hence essential for maternal behavior. Furthermore, HFD feeding resulted in increased circulating levels of maternal corticosterone and decreased levels of leptin. In addition, the activity of the protective 11β-dehydrogenase-2 (11β-HSD-2) barrier in the placenta was decreased together with 11β-dehydrogenase-1 (11β-HSD-1) gene expression. Overall, these data suggest that HFD acts as a stressful challenge during pregnancy, impairing the neuroendocrine system and the neural activity of brain regions involved in the processing of relevant olfactory stimuli, with negative consequences on maternal physiology and behavior. PMID:26143538

  8. Maternal high-fat diet acts as a stressor increasing maternal glucocorticoids' signaling to the fetus and disrupting maternal behavior and brain activation in C57BL/6J mice.

    PubMed

    Bellisario, Veronica; Panetta, Pamela; Balsevich, Georgia; Baumann, Valentin; Noble, June; Raggi, Carla; Nathan, Olivia; Berry, Alessandra; Seckl, Jonathan; Schmidt, Mathias; Holmes, Megan; Cirulli, Francesca

    2015-10-01

    Maternal diet during pregnancy can impact maternal behavior as well as the intrauterine environment, playing a critical role in programming offspring's physiology. In a preliminary study, we found a strong association between high-fat diet (HFD) during pregnancy and increased cannibalistic episodes and dams' mortality during late pregnancy and parturition. Based upon these data, we hypothesized that HFD during pregnancy could negatively affect neuroendocrine and metabolic regulations occurring during the final stages of pregnancy, thereby disrupting maternal behavior. To test this hypothesis, female C57BL/6J mice were fed HFD or control diet for 11 weeks until three days before the expected delivery date. Basal corticosterone plasma levels and brain levels of c-Fos were measured both before and after delivery, in addition to leptin levels in the adipose tissue. Dam's emotional behavior and social anxiety, in addition to locomotor activity were assessed before parturition. Data show that HFD led to aberrant maternal behavior, dams being characterized by behaviors related to aggression toward an unfamiliar social stimulus in the social avoidance test, in addition to decreased locomotor activity. Neural activity in HFD dams was reduced in the olfactory bulbs, a crucial brain region for social and olfactory recognition hence essential for maternal behavior. Furthermore, HFD feeding resulted in increased circulating levels of maternal corticosterone and decreased levels of leptin. In addition, the activity of the protective 11β-dehydrogenase-2 (11β-HSD-2) barrier in the placenta was decreased together with 11β-dehydrogenase-1 (11β-HSD-1) gene expression. Overall, these data suggest that HFD acts as a stressful challenge during pregnancy, impairing the neuroendocrine system and the neural activity of brain regions involved in the processing of relevant olfactory stimuli, with negative consequences on maternal physiology and behavior.

  9. Piglets with maternally derived antibodies from sows immunized with rAdV-SFV-E2 were completely protected against lethal CSFV challenge.

    PubMed

    Xia, Shui-Li; Du, Mingliang; Lei, Jian-Lin; Liu, Yan; Wang, Yimin; Ji, Shengwei; Xiang, Guang-Tao; Li, Lian-Feng; Cong, Xin; Luo, Yuzi; Shao, Lina; Qiu, Hua-Ji; Sun, Yuan

    2016-07-15

    Classical swine fever (CSF) is an economically important infectious disease of pigs caused by Classical swine fever virus (CSFV). To facilitate the eradication of CSF in endemic areas, a marker vaccine enabling differentiation of infected from vaccinated animals (DIVA) is urgently needed. Previously, we have demonstrated that the DIVA vaccine rAdV-SFV-E2, an adenovirus-vectored Semliki Forest virus replicon expressing the E2 glycoprotein of CSFV, induces complete protection from lethal CSFV challenge. The aim of this study was to investigate whether maternally derived antibodies (MDAs) from sows immunized with rAdV-SFV-E2 can effectively protect piglets against lethal CSFV challenge. Three groups of five-week-old piglets (n=4), with or without MDAs, were challenged with the highly virulent CSFV Shimen strain. Clinical signs, CSFV-specific antibodies, viremia and pathological and histopathological changes were monitored. The results showed that the piglets with MDAs from the sow immunized with rAdV-SFV-E2 were protected clinically, virologically and pathologically, while the piglets with undetectable MDAs from the rAdV-SFV-E2-immunized sow were partially protected (2/4 survival), in contrast with the piglets from the non-vaccinated sow, which displayed CSF-typical clinical signs, viremia, deaths (4/4) and pathological/histopathological lesions. These results indicate that MDAs from the sow immunized with rAdV-SFV-E2 are able to confer full passive immunity to newborn piglets. PMID:27283854

  10. Jungle honey enhances immune function and antitumor activity.

    PubMed

    Fukuda, Miki; Kobayashi, Kengo; Hirono, Yuriko; Miyagawa, Mayuko; Ishida, Takahiro; Ejiogu, Emenike C; Sawai, Masaharu; Pinkerton, Kent E; Takeuchi, Minoru

    2011-01-01

    Jungle honey (JH) is collected from timber and blossom by wild honey bees that live in the tropical forest of Nigeria. JH is used as a traditional medicine for colds, skin inflammation and burn wounds as well as general health care. However, the effects of JH on immune functions are not clearly known. Therefore, we investigated the effects of JH on immune functions and antitumor activity in mice. Female C57BL/6 mice were injected with JH (1 mg/mouse/day, seven times intra-peritoneal). After seven injections, peritoneal cells (PC) were obtained. Antitumor activity was assessed by growth of Lewis Lung Carcinoma/2 (LL/2) cells. PC numbers were increased in JH-injected mice compared to control mice. In Dot Plot analysis by FACS, a new cell population appeared in JH-injected mice. The percent of Gr-1 surface antigen and the intensity of Gr-1 antigen expression of PC were increased in JH-injected mice. The new cell population was neutrophils. JH possessed chemotactic activity for neutrophils. Tumor incidence and weight were decreased in JH-injected mice. The ratio of reactive oxygen species (ROS) producing cells was increased in JH-injected mice. The effective component in JH was fractionized by gel filtration using HPLC and had an approximate molecular weight (MW) of 261. These results suggest that neutrophils induced by JH possess potent antitumor activity mediated by ROS and the effective immune component of JH is substrate of MW 261. PMID:19141489

  11. Immune Activation in the Liver by Nucleic Acids

    PubMed Central

    Sun, Qian; Wang, Qingde; Scott, Melanie J.; Billiar, Timothy R.

    2016-01-01

    Abstract Viral infection in the liver, including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, is a major health problem worldwide, especially in developing countries. The infection triggers a pro-inflammatory response in patients that is crucial for host defense. Recent studies have identified multiple transmembrane and cytosolic receptors that recognize pathogen-derived nucleic acids, and these receptors are essential for driving immune activation in the liver. In addition to sensing DNA/RNA from pathogens, these intracellular receptors can be activated by nucleic acids of host origin in response to sterile injuries. In this review, we discuss the expanding roles of these receptors in both immune and nonimmune cells in the liver. PMID:27350945

  12. Claudin-low bladder tumors are immune infiltrated and actively immune suppressed

    PubMed Central

    Kardos, Jordan; Chai, Shengjie; Mose, Lisle E.; Selitsky, Sara R.; Krishnan, Bhavani; Saito, Ryoichi; Iglesia, Michael D.; Milowsky, Matthew I.; Parker, Joel S.; Kim, William Y.; Vincent, Benjamin G.

    2016-01-01

    We report the discovery of a claudin-low molecular subtype of high-grade bladder cancer that shares characteristics with the homonymous subtype of breast cancer. Claudin-low bladder tumors were enriched for multiple genetic features including increased rates of RB1, EP300, and NCOR1 mutations; increased frequency of EGFR amplification; decreased rates of FGFR3, ELF3, and KDM6A mutations; and decreased frequency of PPARG amplification. While claudin-low tumors showed the highest expression of immune gene signatures, they also demonstrated gene expression patterns consistent with those observed in active immunosuppression. This did not appear to be due to differences in predicted neoantigen burden, but rather was associated with broad upregulation of cytokine and chemokine levels from low PPARG activity, allowing unopposed NFKB activity. Taken together, these results define a molecular subtype of bladder cancer with distinct molecular features and an immunologic profile that would, in theory, be primed for immunotherapeutic response.

  13. Claudin-low bladder tumors are immune infiltrated and actively immune suppressed

    PubMed Central

    Kardos, Jordan; Chai, Shengjie; Mose, Lisle E.; Selitsky, Sara R.; Krishnan, Bhavani; Saito, Ryoichi; Iglesia, Michael D.; Milowsky, Matthew I.; Parker, Joel S.; Kim, William Y.; Vincent, Benjamin G.

    2016-01-01

    We report the discovery of a claudin-low molecular subtype of high-grade bladder cancer that shares characteristics with the homonymous subtype of breast cancer. Claudin-low bladder tumors were enriched for multiple genetic features including increased rates of RB1, EP300, and NCOR1 mutations; increased frequency of EGFR amplification; decreased rates of FGFR3, ELF3, and KDM6A mutations; and decreased frequency of PPARG amplification. While claudin-low tumors showed the highest expression of immune gene signatures, they also demonstrated gene expression patterns consistent with those observed in active immunosuppression. This did not appear to be due to differences in predicted neoantigen burden, but rather was associated with broad upregulation of cytokine and chemokine levels from low PPARG activity, allowing unopposed NFKB activity. Taken together, these results define a molecular subtype of bladder cancer with distinct molecular features and an immunologic profile that would, in theory, be primed for immunotherapeutic response. PMID:27699256

  14. Oxygenated drinking water enhances immune activity in pigs and increases immune responses of pigs during Salmonella typhimurium infection.

    PubMed

    Jung, Bock-Gie; Lee, Jin-A; Lee, Bong-Joo

    2012-12-01

    It has been considered that drinking oxygenated water improves oxygen availability, which may increase vitality and improve immune functions. The present study evaluated the effects of oxygenated drinking water on immune function in pigs. Continuous drinking of oxygenated water markedly increased peripheral blood mononuclear cell proliferation, interleukin-1β expression level and the CD4(+):CD8(+) cell ratio in pigs. During Salmonella Typhimurium infection, total leukocytes and relative cytokines expression levels were significantly increased in pigs consuming oxygenated water compared with pigs consuming tap water. These findings suggest that oxygenated drinking water enhances immune activity in pigs and increases immune responses of pigs during S. Typhimurium Infection.

  15. Prenatal immune challenge in rats: altered responses to dopaminergic and glutamatergic agents, prepulse inhibition of acoustic startle, and reduced route-based learning as a function of maternal body weight gain after prenatal exposure to poly IC.

    PubMed

    Vorhees, Charles V; Graham, Devon L; Braun, Amanda A; Schaefer, Tori L; Skelton, Matthew R; Richtand, Neil M; Williams, Michael T

    2012-08-01

    Prenatal maternal immune activation has been used to test the neurodevelopmental hypothesis of schizophrenia. Most of the data are in mouse models; far less is available for rats. We previously showed that maternal weight change in response to the immune activator polyinosinic-polycytidylic acid (Poly IC) in rats differentially affects offspring. Therefore, we treated gravid Harlan Sprague-Dawley rats i.p. on embryonic day 14 with 8 mg/kg of Poly IC or Saline. The Poly IC group was divided into those that lost or gained the least weight, Poly IC (L), versus those that gained the most weight, Poly IC (H), following treatment. The study design controlled for litter size, litter sampling, sex distribution, and test experience. We found no effects of Poly IC on elevated zero maze, open-field activity, object burying, light-dark test, straight channel swimming, Morris water maze spatial acquisition, reversal, or shift navigation or spatial working or reference memory, or conditioned contextual or cued fear or latent inhibition. The Poly IC (H) group showed a significant decrease in the rate of route-based learning when visible cues were unavailable in the Cincinnati water maze and reduced prepulse inhibition of acoustic startle in females, but not males. The Poly IC (L) group exhibited altered responses to acute pharmacological challenges: exaggerated hyperactivity in response to (+)-amphetamine and an attenuated hyperactivity in response to MK-801. This model did not exhibit the cognitive, or latent inhibition deficits reported in Poly IC-treated rats but showed changes in response to drugs acting on neurotransmitter systems implicated in the pathophysiology of schizophrenia (dopaminergic hyperfunction and glutamatergic hypofunction).

  16. Maternal uterine natural killer cells nurture fetal growth: in medio stat virtus.

    PubMed

    Colucci, Francesco; Kieckbusch, Jens

    2015-02-01

    Much research in reproductive immunology is preoccupied with maternal tolerance of the semi-allogeneic fetus. This inevitably leads to the assumption that the maternal immune system should be suppressed, similarly to the immunosuppression needed to avoid rejection of an allograft. However, the parallels with transplantation immunology are misleading, and we discuss how interactions between variable immune system genes expressed on maternal natural killer (NK) cells and on the fetal trophoblast modulate fetal growth. Exaggerated suppression or activation of maternal NK cells associates with both extremes of birth weight.

  17. Evidence for the essentiality of arachidonic and docosahexaenoic acid in the postnatal maternal and infant diet for the development of the infant's immune system early in life.

    PubMed

    Richard, Caroline; Lewis, Erin D; Field, Catherine J

    2016-05-01

    Long-chain polyunsaturated fatty acids (LCPUFA), especially the balance between arachidonic (AA) and docosahexaenoic (DHA) acids are known to have important immunomodulatory roles during the postnatal period when the immune system is rapidly developing. AA and DHA are required in infant formula in many countries but are optional in North America. The rationale for adding these LCPUFA to full-term formula is based on their presence in breast milk and randomized controlled studies that suggest improved cognitive function in preterm infants, but results are more variable in full-term infants. Recently, the European Food Safety Authority has proposed, based on a lack of functional evidence, that AA is not required in infant formula for full-term infants during the first year of life but DHA should remain mandatory. The purpose of this review is to review the evidence from epidemiological and intervention studies regarding the essentiality of AA and DHA in the postnatal infant and maternal diet (breast-feeding) for the immune system development early in life. Although studies support the essentiality of DHA for the immune system development, more research is needed to rule out the essentiality of AA. Nevertheless, intervention studies have demonstrated improvement in many markers of immune function in infants fed formula supplemented with AA and DHA compared with unsupplemented formula, which appears to consistently result in beneficial health outcomes including reduction in the risk of developing allergic and atopic disease early in life.

  18. Maternal vaccination: moving the science forward

    PubMed Central

    Faucette, Azure N.; Unger, Benjamin L.; Gonik, Bernard; Chen, Kang

    2015-01-01

    BACKGROUND Infections remain one of the leading causes of morbidity in pregnant women and newborns, with vaccine-preventable infections contributing significantly to the burden of disease. In the past decade, maternal vaccination has emerged as a promising public health strategy to prevent and combat maternal, fetal and neonatal infections. Despite a number of universally recommended maternal vaccines, the development and evaluation of safe and effective maternal vaccines and their wide acceptance are hampered by the lack of thorough understanding of the efficacy and safety in the pregnant women and the offspring. METHODS An outline was synthesized based on the current status and major gaps in the knowledge of maternal vaccination. A systematic literature search in PUBMED was undertaken using the key words in each section title of the outline to retrieve articles relevant to pregnancy. Articles cited were selected based on relevance and quality. On the basis of the reviewed information, a perspective on the future directions of maternal vaccination research was formulated. RESULTS Maternal vaccination can generate active immune protection in the mother and elicit systemic immunoglobulin G (IgG) and mucosal IgG, IgA and IgM responses to confer neonatal protection. The maternal immune system undergoes significant modulation during pregnancy, which influences responsiveness to vaccines. Significant gaps exist in our knowledge of the efficacy and safety of maternal vaccines, and no maternal vaccines against a large number of old and emerging pathogens are available. Public acceptance of maternal vaccination has been low. CONCLUSIONS To tackle the scientific challenges of maternal vaccination and to provide the public with informed vaccination choices, scientists and clinicians in different disciplines must work closely and have a mechanistic understanding of the systemic, reproductive and mammary mucosal immune responses to vaccines. The use of animal models should be

  19. Human Ebola virus infection results in substantial immune activation.

    PubMed

    McElroy, Anita K; Akondy, Rama S; Davis, Carl W; Ellebedy, Ali H; Mehta, Aneesh K; Kraft, Colleen S; Lyon, G Marshall; Ribner, Bruce S; Varkey, Jay; Sidney, John; Sette, Alessandro; Campbell, Shelley; Ströher, Ute; Damon, Inger; Nichol, Stuart T; Spiropoulou, Christina F; Ahmed, Rafi

    2015-04-14

    Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10-50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1-2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients' discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus. PMID:25775592

  20. Human Ebola virus infection results in substantial immune activation.

    PubMed

    McElroy, Anita K; Akondy, Rama S; Davis, Carl W; Ellebedy, Ali H; Mehta, Aneesh K; Kraft, Colleen S; Lyon, G Marshall; Ribner, Bruce S; Varkey, Jay; Sidney, John; Sette, Alessandro; Campbell, Shelley; Ströher, Ute; Damon, Inger; Nichol, Stuart T; Spiropoulou, Christina F; Ahmed, Rafi

    2015-04-14

    Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10-50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1-2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients' discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.

  1. Inflammatory and Immune Activation in Intestinal Myofibroblasts Is Developmentally Regulated

    PubMed Central

    Zawahir, Sharmila; Li, Guanghui; Banerjee, Aditi; Shiu, Jessica; Blanchard, Thomas G.

    2015-01-01

    We previously demonstrated that intestinal myofibroblasts from immature tissue produce excessive IL-8 in response to Escherichia coli lipopolysaccharide (LPS) compared to cells from mature tissue. However, it is unknown whether other cytokines and TLR agonists contribute to this developmentally regulated response. The aim of this study was to further characterize differences in inflammatory signaling in human primary intestinal fibroblasts from fetal (FIF) and infant (IIF) tissue and examine their potential to activate the adaptive immune response in vitro. Cytokine profiles of LPS-stimulated FIF and IIF were assessed by cytokine profile array. IL-8, IL-6, and IL-10 production in response to TLR2, TLR2/6, TLR4, and TLR5 agonists was determined by quantitative ELISA. The potential of activated myofibroblasts to activate adaptive immunity was determined by measuring surface class II MHC expression using flow cytometry. LPS-stimulated FIF produced a distinct proinflammatory cytokine profile consisting of MCP-1, GRO-alpha, IL-6, and IL-8 expression. FIF produced significant IL-8 and IL-6 in response to TLR4 agonist. IIF produced significant levels of IL-8 and IL-6 in the presence of TLR5 and TLR2 agonists. IFN-γ-treated FIF expressed greater HLA-DR levels compared to unstimulated controls and IFN-γ- and LPS-treated IIF. Activated FIF produce a more diverse inflammatory cytokine profile and greater levels of IL-8 and IL-6 in response to TLR4 stimulation compared to IIF. FIF express class II MHC proteins associated with activation of the adaptive immune response. These data suggest that FIF may contribute to bacterial-associated gut inflammation in the immature intestine. PMID:26101946

  2. Immune parameters differentiating active from latent tuberculosis infection in humans.

    PubMed

    Lee, Ji Yeon; Jung, Young Won; Jeong, Ina; Joh, Joon-Sung; Sim, Soo Yeon; Choi, Boram; Jee, Hyeon-Gun; Lim, Dong-Gyun

    2015-12-01

    Tuberculosis remains a highly prevalent infectious disease worldwide. Identification of the immune parameters that differentiate active disease from latent infection will facilitate the development of efficient control measures as well as new diagnostic modalities for tuberculosis. Here, we investigated the cytokine production profiles of monocytes and CD4(+) T lymphocytes upon encountering mycobacterial antigens. In addition, cytokines and lipid mediators with immune-modulating activities were examined in plasma samples ex vivo. Comparison of these parameters in active tuberculosis patients and healthy subjects with latent infection revealed that, active tuberculosis was associated with diminished Th1-type cytokine secretion from CD4(+) T cells and less augmented inflammatory cytokine secretion from monocytes induced by IFN-γ than that in latent tuberculosis infection. In addition, a higher plasma concentration of lipoxin A4 and lower ratio of prostaglandin E2 to lipoxin A4 were observed in active cases than in latent infections. These findings have implications for preparing new therapeutic strategies and for differential diagnosis of the two types of tuberculosis infection.

  3. Does Severe Maternal Morbidity Affect Female Sexual Activity and Function? Evidence from a Brazilian Cohort Study

    PubMed Central

    Andreucci, Carla B.; Cecatti, José G.; Pacagnella, Rodolfo C.; Silveira, Carla; Parpinelli, Mary A.; Ferreira, Elton C.; Angelini, Carina R.; Santos, Juliana P.; Zanardi, Dulce M.; Bussadori, Jamile C.; Cecchino, Gustavo N.; Souza, Renato T.; Sousa, Maria H.; Costa, Maria L.

    2015-01-01

    Objective to assess Female Sexual Function Index (FSFI) scores and delay to resume sexual activity associated with a previous severe maternal morbidity. Method This was a multidimensional retrospective cohort study. Women who gave birth at a Brazilian tertiary maternity between 2008 and 2012 were included, with data extraction from the hospital information system. Those with potentially life-threatening conditions and maternal near miss episodes (severe maternal morbidity) were considered the exposed group. The control group was a random sample of women who had had uncomplicated pregnancy. Female sexual function was evaluated through FSFI questionnaire, and general and reproductive aspects were addressed through specific questions. Statistical analyses were performed using Mann-Whitney and Pearson´s Chi-square for bivariate analyses. Logistic regression was used to identify variables independently associated with lower FSFI scores. Results 638 women were included (315 at exposed and 323 at not exposed groups). The majority of women were under 30 years-old in the control group and between 30 and 46 years-old in the exposed group (p = 0.003). Women who experienced severe maternal morbidity (SMM) had statistically significant differences regarding cesarean section (82.4% versus 47.1% among deliveries without complications, p<0.001), and some previous pathological conditions. FSFI mean scores were similar among groups ranging from 24.39 to 24.42. It took longer for exposed women to resume sexual activity after index pregnancy (mean 84 days after SMM and 65 days for control group, p = 0.01). Multiple analyses showed no significant association of FSFI below cut-off value with any predictor. Conclusion FSFI scores were not different in both groups. However, they were lower than expected. SMM delayed resumption of sexual activity after delivery, beyond postpartum period. However, the proportion of women in both groups having sex at 3 months after delivery was similar

  4. Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity

    PubMed Central

    Xie, Shanshan; Spelmink, Laura; Codemo, Mario; Subramanian, Karthik; Pütsep, Katrin

    2016-01-01

    The traditional Chinese medicine Chan-Su is widely used for treatment of cancer and cardiovascular diseases, but also as a remedy for infections such as furunculosis, tonsillitis and acute pharyngitis. The clinical use of Chan-Su suggests that it has anti-infective effects, however, the mechanism of action is incompletely understood. In particular, the effect on the human immune system is poorly defined. Here, we describe previously unrecognized immunomodulatory activities of cinobufagin (CBG), a major bioactive component of Chan-Su. Using human monocyte-derived dendritic cells (DCs), we show that LPS-induced maturation and production of a number of cytokines was potently inhibited by CBG, which also had a pro-apoptotic effect, associated with activation of caspase-3. Interestingly, CBG triggered caspase-1 activation and significantly enhanced IL-1β production in LPS-stimulated cells. Finally, we demonstrate that CBG upregulates gene expression of the antimicrobial peptides (AMPs) hBD-2 and hBD-3 in DCs, and induces secretion of HNP1-3 and hCAP-18/LL-37 from neutrophils, potentiating neutrophil antibacterial activity. Taken together, our data indicate that CBG modulates the inflammatory phenotype of DCs in response to LPS, and triggers an antibacterial innate immune response, thus proposing possible mechanisms for the clinical effects of Chan-Su in anti-infective therapy. PMID:27529866

  5. Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity.

    PubMed

    Xie, Shanshan; Spelmink, Laura; Codemo, Mario; Subramanian, Karthik; Pütsep, Katrin; Henriques-Normark, Birgitta; Olliver, Marie

    2016-01-01

    The traditional Chinese medicine Chan-Su is widely used for treatment of cancer and cardiovascular diseases, but also as a remedy for infections such as furunculosis, tonsillitis and acute pharyngitis. The clinical use of Chan-Su suggests that it has anti-infective effects, however, the mechanism of action is incompletely understood. In particular, the effect on the human immune system is poorly defined. Here, we describe previously unrecognized immunomodulatory activities of cinobufagin (CBG), a major bioactive component of Chan-Su. Using human monocyte-derived dendritic cells (DCs), we show that LPS-induced maturation and production of a number of cytokines was potently inhibited by CBG, which also had a pro-apoptotic effect, associated with activation of caspase-3. Interestingly, CBG triggered caspase-1 activation and significantly enhanced IL-1β production in LPS-stimulated cells. Finally, we demonstrate that CBG upregulates gene expression of the antimicrobial peptides (AMPs) hBD-2 and hBD-3 in DCs, and induces secretion of HNP1-3 and hCAP-18/LL-37 from neutrophils, potentiating neutrophil antibacterial activity. Taken together, our data indicate that CBG modulates the inflammatory phenotype of DCs in response to LPS, and triggers an antibacterial innate immune response, thus proposing possible mechanisms for the clinical effects of Chan-Su in anti-infective therapy. PMID:27529866

  6. Activating Transcription Factor 3 Regulates Immune and Metabolic Homeostasis

    PubMed Central

    Rynes, Jan; Donohoe, Colin D.; Frommolt, Peter; Brodesser, Susanne; Jindra, Marek

    2012-01-01

    Integration of metabolic and immune responses during animal development ensures energy balance, permitting both growth and defense. Disturbed homeostasis causes organ failure, growth retardation, and metabolic disorders. Here, we show that the Drosophila melanogaster activating transcription factor 3 (Atf3) safeguards metabolic and immune system homeostasis. Loss of Atf3 results in chronic inflammation and starvation responses mounted primarily by the larval gut epithelium, while the fat body suffers lipid overload, causing energy imbalance and death. Hyperactive proinflammatory and stress signaling through NF-κB/Relish, Jun N-terminal kinase, and FOXO in atf3 mutants deregulates genes important for immune defense, digestion, and lipid metabolism. Reducing the dose of either FOXO or Relish normalizes both lipid metabolism and gene expression in atf3 mutants. The function of Atf3 is conserved, as human ATF3 averts some of the Drosophila mutant phenotypes, improving their survival. The single Drosophila Atf3 may incorporate the diversified roles of two related mammalian proteins. PMID:22851689

  7. Maternally Derived Immunity Extends Swine Influenza A Virus Persistence within Farrow-to-Finish Pig Farms: Insights from a Stochastic Event-Driven Metapopulation Model

    PubMed Central

    Cador, Charlie; Rose, Nicolas; Willem, Lander; Andraud, Mathieu

    2016-01-01

    Swine Influenza A Viruses (swIAVs) have been shown to persist in farrow-to-finish pig herds with repeated outbreaks in successive batches, increasing the risk for respiratory disorders in affected animals and being a threat for public health. Although the general routes of swIAV transmission (i.e. direct contact and exposure to aerosols) were clearly identified, the transmission process between batches is still not fully understood. Maternally derived antibodies (MDAs) were stressed as a possible factor favoring within-herd swIAV persistence. However, the relationship between MDAs and the global spread among the different subpopulations in the herds is still lacking. The aim of this study was therefore to understand the mechanisms induced by MDAs in relation with swIAV spread and persistence in farrow-to-finish pig herds. A metapopulation model has been developed representing the population dynamics considering two subpopulations—breeding sows and growing pigs—managed according to batch-rearing system. This model was coupled with a swIAV-specific epidemiological model, accounting for partial passive immunity protection in neonatal piglets and an immunity boost in re-infected animals. Airborne transmission was included by a between-room transmission rate related to the current prevalence of shedding pigs. Maternally derived partial immunity in piglets was found to extend the duration of the epidemics within their batch, allowing for efficient between-batch transmission and resulting in longer swIAV persistence at the herd level. These results should be taken into account in the design of control programmes for the spread and persistence of swIAV in swine herds. PMID:27662592

  8. Evidence for active maternal-fetal transport of Na+ across the placenta of the anaesthetized rat.

    PubMed

    Stulc, J; Stulcová, B; Sibley, C P

    1993-10-01

    1. In order to investigate mechanisms of Na+ transfer, the unidirectional maternal-fetal clearance (Kmf) of 22Na+ and of 51Cr-EDTA (a marker of paracellular diffusion) was measured across the intact or umbilically or dually perfused placenta of the anaesthetized rat. 2. The Kmf of 22Na+ in the intact preparation (18.5 +/- 2.7 microliters min-1, mean +/- S.D., n = 105 placentas) exceeded that of 51Cr-EDTA in the same experiments (1.4 +/- 0.3 microliters min-1) by more than ten times, whereas the difference in their diffusion coefficients in water was only 2-fold. In the perfused preparations the difference in the Kmf values was 6-fold. 3. Assuming that a simple model of paracellular diffusion through wide pores was one component of transfer, the Kmf of 51Cr-EDTA and the diffusion coefficients were used to calculate a component of 22Na+ clearance (Kmf,residual) and of Na+ flux (Jmf,residual) across the perfused placentas which could not be accounted for by transfer through the paracellular route. 4. Kmf,residual of 22Na+ across the dually perfused placenta was significantly lower when temperature was reduced, the temperature quotient (Q10) of the transfer being about 2. Kmf,residual was also significantly lower when 0.1 mM ouabain was perfused on the fetal side. Jmf,residual exhibited saturation kinetics characterized by an apparent Michaelis constant (Km) of 90 mM. Kmf,residual was not influenced by 0.5 mM frusemide, 0.5 mM amiloride or by 0.5 mM hydrochlorothiazide administered to the maternal side. It was significantly increased by 1 mM alanine on the maternal side suggesting that the coupled transfer of Na+ and amino acids may contribute significantly to the maternal-fetal flux of Na+. 5. These observations suggest that most (80%) of the maternal-fetal flux of Na+ across the rat placenta is effected by active transcellular transport. This transport involves passive entry of Na+ into the trophoblast from the maternal side by a largely unknown saturable mechanism

  9. Immune activation during cerebellar dysfunction following Plasmodium falciparum malaria.

    PubMed

    de Silva, H J; Hoang, P; Dalton, H; de Silva, N R; Jewell, D P; Peiris, J B

    1992-01-01

    Evidence for immune activation was investigated in 12 patients with a rare syndrome of self-limiting, delayed onset cerebellar dysfunction following an attack of falciparum malaria which occurred 18-26 d previously. Concentrations of tumour necrosis factor, interleukin 6 and interleukin 2 were all significantly higher in serum samples of patients during cerebellar ataxia than in recovery sera and in the sera of 8 patients who did not develop delayed cerebellar dysfunction following an attack of falciparum malaria. Cytokine concentrations in the cerebrospinal fluid were also significantly higher in ataxic patients than in controls. These findings suggest that immunological mechanisms may play a role in delayed cerebellar dysfunction following falciparum malaria.

  10. Maternal caffeine exposure alters neuromotor development and hippocampus acetylcholinesterase activity in rat offspring.

    PubMed

    Souza, Ana Claudia; Souza, Andressa; Medeiros, Liciane Fernandes; De Oliveira, Carla; Scarabelot, Vanessa Leal; Da Silva, Rosane Souza; Bogo, Mauricio Reis; Capiotti, Katiucia Marques; Kist, Luiza Wilges; Bonan, Carla D; Caumo, Wolnei; Torres, Iraci L S

    2015-01-21

    The objective of this study was to evaluate the effects of maternal caffeine intake on the neuromotor development of rat offspring and on acetylcholine degradation and acetylcholinesterase (AChE) expression in the hippocampus of 14-day-old infant rats. Rat dams were treated with caffeine (0.3g/L) throughout gestation and lactation until the pups were 14 days old. The pups were divided into three groups: (1) control, (2) caffeine, and (3) washout caffeine. The washout group received a caffeine solution until the seventh postnatal day (P7). Righting reflex (RR) and negative geotaxis (NG) were assessed to evaluate postural parameters as an index of neuromotor reflexes. An open-field (OF) test was conducted to assess locomotor and exploratory activities as well as anxiety-like behaviors. Caffeine treatment increased both RR and NG latency times. In the OF test, the caffeine group had fewer outer crossings and reduced locomotion compared to control, while the washout group showed increased inner crossings in relation to the other groups and fewer rearings only in comparison to the control group. We found decreased AChE activity in the caffeine group compared to the other groups, with no alteration in AChE transcriptional regulation. Chronic maternal exposure to caffeine promotes important alterations in neuromotor development. These results highlight the ability of maternal caffeine intake to interfere with cholinergic neurotransmission during brain development.

  11. Exposure analysis methods impact associations between maternal physical activity and cesarean delivery

    PubMed Central

    Bovbjerg, Marit L.; Siega-Riz, Anna Maria; Evenson, Kelly R.; Goodnight, William

    2015-01-01

    Background Previous studies report conflicting results regarding a possible association between maternal physical activity (PA) and cesarean delivery. Methods 7-day PA recalls were collected by telephone from n=1205 pregnant women from North Carolina, without prior cesarean, during two time windows: 17-22 weeks and 27-30 weeks completed gestation. PA was treated as a continuous, non-linear variable in binomial regressions (log-link function); models controlled for primiparity, maternal contraindications to exercise, pre-eclampsia, pregravid BMI, and percent poverty. We examined both total PA and moderate-to-vigorous PA (MVPA) at each time. Outcomes data came from medical records. Results The dose-response curves between PA or MVPA and cesarean risk at 17-22 weeks followed an inverse J-shape, but at 27-30 weeks the curves reversed and were J-shaped. However, only (total) PA at 27-30 weeks was strongly associated with cesarean risk; this association was attenuated when women reporting large volumes of PA (>97.5th percentile) were excluded. Conclusion We did not find evidence of an association between physical activity and cesarean birth. We did, however, find evidence that associations between PA and risk of cesarean may be non-linear and dependent on gestational age at time of exposure, limiting the accuracy of analyses that collapse maternal PA into categories. PMID:24509873

  12. Effects of early life stress on brain activity: implications from maternal separation model in rodents.

    PubMed

    Nishi, Mayumi; Horii-Hayashi, Noriko; Sasagawa, Takayo; Matsunaga, Wataru

    2013-01-15

    Adverse experiences in early life can affect the formation of neuronal circuits during postnatal development and exert long-lasting influences on neural function. Many studies have shown that daily repeated maternal separation (RMS), an animal model of early life stress, can modulate the hypothalamic-pituitary-adrenal axis (HPA-axis) and can affect subsequent brain function and emotional behavior during adulthood. However, the molecular basis of the long-lasting effects of early life stress on brain function has not been completely elucidated. In this mini-review, we introduce various cases of maternal separation in rodents and illustrate the alterations in HPA-axis activity by focusing on corticosterone (CORT), an end-product of the HPA-axis in rodents. We then present the characterization of the brain regions affected by various patterns of MS, including RMS and single time maternal separation (SMS) at various stages before weaning, by investigating c-Fos expression, a biological marker of neuronal activity. These CORT and c-Fos studies suggest that repeated early life stress may affect neuronal function in region- and temporal-specific manners, indicating a critical period for habituation to early life stress. Furthermore, we introduce changes in behavioral aspects and gene expression in adult mice exposed to RMS.

  13. Maternal caffeine exposure alters neuromotor development and hippocampus acetylcholinesterase activity in rat offspring.

    PubMed

    Souza, Ana Claudia; Souza, Andressa; Medeiros, Liciane Fernandes; De Oliveira, Carla; Scarabelot, Vanessa Leal; Da Silva, Rosane Souza; Bogo, Mauricio Reis; Capiotti, Katiucia Marques; Kist, Luiza Wilges; Bonan, Carla D; Caumo, Wolnei; Torres, Iraci L S

    2015-01-21

    The objective of this study was to evaluate the effects of maternal caffeine intake on the neuromotor development of rat offspring and on acetylcholine degradation and acetylcholinesterase (AChE) expression in the hippocampus of 14-day-old infant rats. Rat dams were treated with caffeine (0.3g/L) throughout gestation and lactation until the pups were 14 days old. The pups were divided into three groups: (1) control, (2) caffeine, and (3) washout caffeine. The washout group received a caffeine solution until the seventh postnatal day (P7). Righting reflex (RR) and negative geotaxis (NG) were assessed to evaluate postural parameters as an index of neuromotor reflexes. An open-field (OF) test was conducted to assess locomotor and exploratory activities as well as anxiety-like behaviors. Caffeine treatment increased both RR and NG latency times. In the OF test, the caffeine group had fewer outer crossings and reduced locomotion compared to control, while the washout group showed increased inner crossings in relation to the other groups and fewer rearings only in comparison to the control group. We found decreased AChE activity in the caffeine group compared to the other groups, with no alteration in AChE transcriptional regulation. Chronic maternal exposure to caffeine promotes important alterations in neuromotor development. These results highlight the ability of maternal caffeine intake to interfere with cholinergic neurotransmission during brain development. PMID:25451122

  14. Establishment of regions of genomic activity during the Drosophila maternal to zygotic transition.

    PubMed

    Li, Xiao-Yong; Harrison, Melissa M; Villalta, Jacqueline E; Kaplan, Tommy; Eisen, Michael B

    2014-01-01

    We describe the genome-wide distributions and temporal dynamics of nucleosomes and post-translational histone modifications throughout the maternal-to-zygotic transition in embryos of Drosophila melanogaster. At mitotic cycle 8, when few zygotic genes are being transcribed, embryonic chromatin is in a relatively simple state: there are few nucleosome free regions, undetectable levels of the histone methylation marks characteristic of mature chromatin, and low levels of histone acetylation at a relatively small number of loci. Histone acetylation increases by cycle 12, but it is not until cycle 14 that nucleosome free regions and domains of histone methylation become widespread. Early histone acetylation is strongly associated with regions that we have previously shown to be bound in early embryos by the maternally deposited transcription factor Zelda, suggesting that Zelda triggers a cascade of events, including the accumulation of specific histone modifications, that plays a role in the subsequent activation of these sequences. PMID:25313869

  15. Immunization.

    ERIC Educational Resources Information Center

    Guerin, Nicole; And Others

    1986-01-01

    Contents of this double journal issue concern immunization and primary health care of children. The issue decribes vaccine storage and sterilization techniques, giving particular emphasis to the role of the cold chain, i.e., the maintenance of a specific temperature range to assure potency of vaccines as they are moved from a national storage…

  16. Biparental immune priming in the pipefish Syngnathus typhle.

    PubMed

    Beemelmanns, Anne; Roth, Olivia

    2016-08-01

    The transfer of immunity from parents to offspring (trans-generational immune priming (TGIP)) boosts offspring immune defence and parasite resistance. TGIP is usually a maternal trait. However, if fathers have a physical connection to their offspring, and if offspring are born in the paternal parasitic environment, evolution of paternal TGIP can become adaptive. In Syngnathus typhle, a sex-role reversed pipefish with male pregnancy, both parents invest into offspring immune defence. To connect TGIP with parental investment, we need to know how parents share the task of TGIP, whether TGIP is asymmetrically distributed between the parents, and how the maternal and paternal effects interact in case of biparental TGIP. We experimentally investigated the strength and differences but also the costs of maternal and paternal contribution, and their interactive biparental influence on offspring immune defence throughout offspring maturation. To disentangle maternal and paternal influences, two different bacteria were used in a fully reciprocal design for parental and offspring exposure. In offspring, we measured gene expression of 29 immune genes, 15 genes associated with epigenetic regulation, immune cell activity and life-history traits. We identified asymmetric maternal and paternal immune priming with a dominating, long-lasting paternal effect. We could not detect an additive adaptive biparental TGIP impact. However, biparental TGIP harbours additive costs as shown in delayed sexual maturity. Epigenetic regulation may play a role both in maternal and paternal TGIP.

  17. Prenatal interaction of mutant DISC1 and immune activation produces adult psychopathology

    PubMed Central

    Abazyan, B.; Nomura, J.; Kannan, G.; Ishizuka, K.; Tamashiro, K. L. K.; Nucifora, F.; Pogorelov, V.; Ladenheim, B.; Yang, C.; Krasnova, I. N.; Cadet, J. L.; Pardo, C.; Mori, S.; Kamiya, A.; Vogel, M.; Sawa, A.; Ross, C. A.; Pletnikov, M. V.

    2010-01-01

    Background Gene-environment interactions (GEI) are involved in the pathogenesis of mental diseases. We evaluated interaction between mutant human Disrupted-In-Schizophrenia-1 (mhDISC1) and maternal immune activation implicated in schizophrenia and mood disorders. Methods Pregnant mice were treated with saline or polyinosinic:polycytidylic acid (Poly I:C) at gestation day 9. Levels of inflammatory cytokines were measured in fetal and adult brains, expression of mhDISC1, endogenous DISC1, LIS1, NDEL1, gp130, Grb2, and GSK-3β were assessed in cortical samples of newborn mice. Tissue content of monoamines, volumetric brain abnormalities, dendritic spine density in the hippocampus and various domains of the mouse behavior repertoire were evaluated in adult male mice. Results Prenatal interaction produced anxiety, depression-like responses, and altered pattern of social behavior. These behaviors were accompanied by decreased reactivity of the HPA axis, attenuated 5-HT neurotransmission in the hippocampus, reduced enlargement of lateral ventricles, decreased volumes of amygdala and periaqueductal gray matter and density of spines on dendrites of granule cells of the hippocampus. Prenatal interaction modulated secretion of inflammatory cytokines in fetal brains, levels of mhDISC1, endogenous mouse DISC1, and GSK-3β. The behavioral effects of GEI were observed only if mhDISC1 was expressed throughout the life span. Conclusions Prenatal immune activation interacted with mhDISC1 to produce the neurobehavioral phenotypes that were not seen in untreated mhDISC1 mice and that resemble aspects of major mental illnesses, including mood disorders. We propose that our DISC1 mouse model is a valuable system to study the molecular pathways underlying GEI relevant to mental illnesses. PMID:21130225

  18. Association of IL-4 and IL-10 maternal haplotypes with immune responses to P. falciparum in mothers and newborns

    PubMed Central

    2013-01-01

    Background Particular cytokine gene polymorphisms are involved in the regulation of the antibody production. The consequences of already described IL-4, IL-10 and IL-13 gene polymorphisms on biological parameters and antibody levels were investigated among 576 mothers at delivery and their newborns in the context of P. falciparum placental malaria infection. Methods The study took place in the semi-rural area of Tori-Bossito, in south-west Benin, where malaria is meso-endemic. Six biallelic polymorphisms were determined by quantitative PCR using TaqMan® Pre-Designed SNP Genotyping Assays, in IL-4 (rs2243250, rs2070874), IL-10 (rs1800896, rs1800871, rs1800872) and IL-13 (rs1800925) genes. Antibody responses directed to P. falciparum MSP-1, MSP-2, MSP-3, GLURP-R0, GLURP-R2 and AMA-1 recombinant proteins were determined by ELISA. Results The maternal IL-4−590*T/IL-4+33*T haplotype (one or two copies) was associated with favorable maternal condition at delivery (high haemoglobin levels, absence of placental parasites) and one of its component, the IL-4−590TT genotype, was related to low IgG levels to MSP-1, MSP-2/3D7 and MSP-2/FC27. Inversely, the maternal IL-10−1082AA was positively associated with P. falciparum placenta infection at delivery. As a consequence, the IL-10−819*T allele (in CT and TT genotypes) as well as the IL-10−1082*A/IL-10−819*T/IL-10−592*A haplotype (one or two copies) in which it is included, were related to an increased risk for anaemia in newborns. The maternal IL-10−1082AA genotype was related to high IgG levels to MSP-2/3D7 and AMA-1 in mothers and newborns, respectively. The IL-13 gene polymorphism was only involved in the newborn’s antibody response to AMA-1. Conclusion These data revealed that IL-4 and IL-10 maternal gene polymorphisms are likely to play a role in the regulation of biological parameters in pregnant women at delivery (anaemia, P. falciparum placenta infection) and in newborns (anaemia). Moreover, IL-4, IL

  19. Activation of cellular immune response in acute pancreatitis.

    PubMed Central

    Mora, A; Pérez-Mateo, M; Viedma, J A; Carballo, F; Sánchez-Payá, J; Liras, G

    1997-01-01

    BACKGROUND: Inflammatory mediators have recently been implicated as potential markers of severity in acute pancreatitis. AIMS: To determine the value of neopterin and polymorphonuclear (PMN) elastase as markers of activation of cellular immunity and as early predictors of disease severity. PATIENTS: Fifty two non-consecutive patients classified according to their clinical outcome into mild (n = 26) and severe pancreatitis (n = 26). METHODS: Neopterin in serum and the PMN elastase/A1PI complex in plasma were measured during the first three days of hospital stay. RESULTS: Within three days after the onset of acute pancreatitis, PMN elastase was significantly higher in the severe pancreatitis group. Patients with severe disease also showed significantly higher values of neopterin on days 1 and 2 but not on day 3 compared with patients with mild disease. There was a significant correlation between PMN elastase and neopterin values on days 1 and 2. PMN elastase on day 1 predicted disease severity with a sensitivity of 76.7% and a specificity of 91.6%. Neopterin did not surpass PMN elastase in the probability of predicting disease severity. CONCLUSIONS: These data show that activation of cellular immunity is implicated in the pathogenesis of acute pancreatitis and may be a main contributory factor to disease severity. Neopterin was not superior to PMN elastase in the prediction of severity. PMID:9245935

  20. Microglia mechanics: immune activation alters traction forces and durotaxis

    PubMed Central

    Bollmann, Lars; Koser, David E.; Shahapure, Rajesh; Gautier, Hélène O. B.; Holzapfel, Gerhard A.; Scarcelli, Giuliano; Gather, Malte C.; Ulbricht, Elke; Franze, Kristian

    2015-01-01

    Microglial cells are key players in the primary immune response of the central nervous system. They are highly active and motile cells that chemically and mechanically interact with their environment. While the impact of chemical signaling on microglia function has been studied in much detail, the current understanding of mechanical signaling is very limited. When cultured on compliant substrates, primary microglial cells adapted their spread area, morphology, and actin cytoskeleton to the stiffness of their environment. Traction force microscopy revealed that forces exerted by microglia increase with substrate stiffness until reaching a plateau at a shear modulus of ~5 kPa. When cultured on substrates incorporating stiffness gradients, microglia preferentially migrated toward stiffer regions, a process termed durotaxis. Lipopolysaccharide-induced immune-activation of microglia led to changes in traction forces, increased migration velocities and an amplification of durotaxis. We finally developed a mathematical model connecting traction forces with the durotactic behavior of migrating microglial cells. Our results demonstrate that microglia are susceptible to mechanical signals, which could be important during central nervous system development and pathologies. Stiffness gradients in tissue surrounding neural implants such as electrodes, for example, could mechanically attract microglial cells, thus facilitating foreign body reactions detrimental to electrode functioning. PMID:26441534

  1. Microglia mechanics: immune activation alters traction forces and durotaxis.

    PubMed

    Bollmann, Lars; Koser, David E; Shahapure, Rajesh; Gautier, Hélène O B; Holzapfel, Gerhard A; Scarcelli, Giuliano; Gather, Malte C; Ulbricht, Elke; Franze, Kristian

    2015-01-01

    Microglial cells are key players in the primary immune response of the central nervous system. They are highly active and motile cells that chemically and mechanically interact with their environment. While the impact of chemical signaling on microglia function has been studied in much detail, the current understanding of mechanical signaling is very limited. When cultured on compliant substrates, primary microglial cells adapted their spread area, morphology, and actin cytoskeleton to the stiffness of their environment. Traction force microscopy revealed that forces exerted by microglia increase with substrate stiffness until reaching a plateau at a shear modulus of ~5 kPa. When cultured on substrates incorporating stiffness gradients, microglia preferentially migrated toward stiffer regions, a process termed durotaxis. Lipopolysaccharide-induced immune-activation of microglia led to changes in traction forces, increased migration velocities and an amplification of durotaxis. We finally developed a mathematical model connecting traction forces with the durotactic behavior of migrating microglial cells. Our results demonstrate that microglia are susceptible to mechanical signals, which could be important during central nervous system development and pathologies. Stiffness gradients in tissue surrounding neural implants such as electrodes, for example, could mechanically attract microglial cells, thus facilitating foreign body reactions detrimental to electrode functioning. PMID:26441534

  2. Nocturnal activity patterns of northern myotis (Myotis septentrionalis) during the maternity season in West Virginia (USA)

    USGS Publications Warehouse

    Johnson, J.B.; Edwards, J.W.; Ford, W.M.

    2011-01-01

    Nocturnal activity patterns of northern myotis (Myotis septentrionalis) at diurnal roost trees remain largely uninvestigated. For example, the influence of reproductive status, weather, and roost tree and surrounding habitat characteristics on timing of emergence, intra-night activity, and entrance at their roost trees is poorly known. We examined nocturnal activity patterns of northern myotis maternity colonies during pregnancy and lactation at diurnal roost trees situated in areas that were and were not subjected to recent prescribed fires at the Fernow Experimental Forest, West Virginia from 2007 to 2009. According to exit counts and acoustic data, northern myotis colony sizes were similar between reproductive periods and roost tree settings. However, intra-night activity patterns differed slightly between reproductive periods and roost trees in burned and non-burned areas. Weather variables poorly explained variation in activity patterns during pregnancy, but precipitation and temperature were negatively associated with activity patterns during lactation. ?? Museum and Institute of Zoology PAS.

  3. Metabolic signals and innate immune activation in obesity and exercise.

    PubMed

    Ringseis, Robert; Eder, Klaus; Mooren, Frank C; Krüger, Karsten

    2015-01-01

    The combination of a sedentary lifestyle and excess energy intake has led to an increased prevalence of obesity which constitutes a major risk factor for several co-morbidities including type 2 diabetes and cardiovascular diseases. Intensive research during the last two decades has revealed that a characteristic feature of obesity linking it to insulin resistance is the presence of chronic low-grade inflammation being indicative of activation of the innate immune system. Recent evidence suggests that activation of the innate immune system in the course of obesity is mediated by metabolic signals, such as free fatty acids (FFAs), being elevated in many obese subjects, through activation of pattern recognition receptors thereby leading to stimulation of critical inflammatory signaling cascades, like IκBα kinase/nuclear factor-κB (IKK/NF- κB), endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and NOD-like receptor P3 (NLRP3) inflammasome pathway, that interfere with insulin signaling. Exercise is one of the main prescribed interventions in obesity management improving insulin sensitivity and reducing obesity- induced chronic inflammation. This review summarizes current knowledge of the cellular recognition mechanisms for FFAs, the inflammatory signaling pathways triggered by excess FFAs in obesity and the counteractive effects of both acute and chronic exercise on obesity-induced activation of inflammatory signaling pathways. A deeper understanding of the effects of exercise on inflammatory signaling pathways in obesity is useful to optimize preventive and therapeutic strategies to combat the increasing incidence of obesity and its comorbidities. PMID:25825956

  4. Path to impact: A report from the Bill and Melinda Gates Foundation convening on maternal immunization in resource-limited settings; Berlin - January 29-30, 2015.

    PubMed

    Sobanjo-Ter Meulen, Ajoke; Abramson, Jon; Mason, Elizabeth; Rees, Helen; Schwalbe, Nina; Bergquist, Sharon; Klugman, Keith P

    2015-11-25

    Global initiatives such as the Millennium Development Goals have led to major improvements in the health of women and children, and significant reductions in childhood mortality. Worldwide, maternal mortality has decreased by 45% and under-five mortality has fallen by over 50% over the past two decades [1]. However, improvements have not been achieved evenly across all ages; since 1990, under-five mortality has declined by ∼5% annually, but the average decrease in neonatal mortality is only ∼3% per year. Against this background, the Bill and Melinda Gates Foundation (BMGF) convened a meeting in Berlin on January 29-30, 2015 of global health stakeholders, representing funders, academia, regulatory agencies, non-governmental organizations, vaccine manufacturers, and Ministries of Health from Africa and Asia. The topic of discussion was the potential of maternal immunization (MI) to achieve further improvements in under-five morbidity and mortality rates in children, and particularly neonates and young infants, through targeting infectious diseases that are not preventable by other interventions in these age groups. The meeting focused on effective and appropriately priced MI vaccines against influenza, pertussis, and tetanus, as well as against respiratory syncytial virus, and the group B Streptococcus, for which no licensed vaccines currently exist. The primary goals of the BMGF 2015 convening were to bring together the global stakeholders in vaccine development, policy and delivery together with the Maternal, Newborn and Child Health (MNCH) community, to get recognition that MI is a strategy shared between these groups and so encourage increased collaboration, and obtain alignment on the next steps toward achieving a significant health impact through implementation of a MI program.

  5. Path to impact: A report from the Bill and Melinda Gates Foundation convening on maternal immunization in resource-limited settings; Berlin - January 29-30, 2015.

    PubMed

    Sobanjo-Ter Meulen, Ajoke; Abramson, Jon; Mason, Elizabeth; Rees, Helen; Schwalbe, Nina; Bergquist, Sharon; Klugman, Keith P

    2015-11-25

    Global initiatives such as the Millennium Development Goals have led to major improvements in the health of women and children, and significant reductions in childhood mortality. Worldwide, maternal mortality has decreased by 45% and under-five mortality has fallen by over 50% over the past two decades [1]. However, improvements have not been achieved evenly across all ages; since 1990, under-five mortality has declined by ∼5% annually, but the average decrease in neonatal mortality is only ∼3% per year. Against this background, the Bill and Melinda Gates Foundation (BMGF) convened a meeting in Berlin on January 29-30, 2015 of global health stakeholders, representing funders, academia, regulatory agencies, non-governmental organizations, vaccine manufacturers, and Ministries of Health from Africa and Asia. The topic of discussion was the potential of maternal immunization (MI) to achieve further improvements in under-five morbidity and mortality rates in children, and particularly neonates and young infants, through targeting infectious diseases that are not preventable by other interventions in these age groups. The meeting focused on effective and appropriately priced MI vaccines against influenza, pertussis, and tetanus, as well as against respiratory syncytial virus, and the group B Streptococcus, for which no licensed vaccines currently exist. The primary goals of the BMGF 2015 convening were to bring together the global stakeholders in vaccine development, policy and delivery together with the Maternal, Newborn and Child Health (MNCH) community, to get recognition that MI is a strategy shared between these groups and so encourage increased collaboration, and obtain alignment on the next steps toward achieving a significant health impact through implementation of a MI program. PMID:26314626

  6. The Effects of Maternal Natural (RRR Alpha-Tocopherol Acetate) or Synthetic (All-Rac Alpha-Tocopherol Acetate) Vitamin E Supplementation on Suckling Calf Performance, Colostrum IgG, and Immune Function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to determine the effects of maternally supplemented natural- or synthetic-source vitamin E on suckling calf performance and immune response. In a two-year study, 152 two- and three-year old spring-calving Angus-cross beef cows were blocked by age, BW, and BCS into on...

  7. Divergent immune responses and disease outcomes in piglets immunized with inactivated and attenuated H3N2 swine influenza vaccines in the presence of maternally-derived antibodies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccine-associated enhanced respiratory disease (VAERD) can occur in pigs immunized with whole-inactivated influenza virus (WIV) vaccine and subsequently infected with an antigenically divergent virus of the same HA subtype. Live-attenuated influenza virus (LAIV) vaccines administered intranasally h...

  8. Mediation of the Physical Activity and Healthy Nutrition Behaviors of Preschool Children by Maternal Cognition in China.

    PubMed

    Xu, Xianglong; Sharma, Manoj; Liu, Lingli; Hu, Ping; Zhao, Yong

    2016-01-01

    (1) OBJECTIVE: We aimed to explore the role of social cognitive theory (SCT) of mothers in the physical activity and healthy nutrition behaviors of preschool children; (2) METHODS: We used a self-administered five-point Likert common physical activity and nutrition behaviors scale in Chinese based on a social cognitive theory scale in English with established validity and reliability in the USA. The current study adopted the proportional sampling method to survey mothers of preschool children in four areas-namely, Chongqing, Chengdu, Taiyuan, and Shijiazhuang-of China; (3) RESULTS: We included 1208 mothers (80.0% mothers of normal weight children, age 31.87 ± 4.19 years). Positive correlations were found between maternal social cognition and preschool children's physical activity (PA) behavior (p < 0.0001). However, an insignificant correlation is observed between preschool children's fruits and vegetables (FV) behavior, screen time (ST) behavior, and maternal social cognition; (4) CONCLUSIONS: This study provides some implications for increasing fruit and vegetable consumption, increasing physical activity time, and reducing screen time in preschool children using SCT in China. Maternal social cognition is associated with preschool children's PA behavior, and the results suggest that maternal social cognition may not affect children FV and ST behaviors. Further research is necessary to test the mediation of maternal social cognition on preschool children's ST behavior and the correlations between maternal social cognition and children's ST behavior. PMID:27649215

  9. Mediation of the Physical Activity and Healthy Nutrition Behaviors of Preschool Children by Maternal Cognition in China.

    PubMed

    Xu, Xianglong; Sharma, Manoj; Liu, Lingli; Hu, Ping; Zhao, Yong

    2016-09-13

    (1) OBJECTIVE: We aimed to explore the role of social cognitive theory (SCT) of mothers in the physical activity and healthy nutrition behaviors of preschool children; (2) METHODS: We used a self-administered five-point Likert common physical activity and nutrition behaviors scale in Chinese based on a social cognitive theory scale in English with established validity and reliability in the USA. The current study adopted the proportional sampling method to survey mothers of preschool children in four areas-namely, Chongqing, Chengdu, Taiyuan, and Shijiazhuang-of China; (3) RESULTS: We included 1208 mothers (80.0% mothers of normal weight children, age 31.87 ± 4.19 years). Positive correlations were found between maternal social cognition and preschool children's physical activity (PA) behavior (p < 0.0001). However, an insignificant correlation is observed between preschool children's fruits and vegetables (FV) behavior, screen time (ST) behavior, and maternal social cognition; (4) CONCLUSIONS: This study provides some implications for increasing fruit and vegetable consumption, increasing physical activity time, and reducing screen time in preschool children using SCT in China. Maternal social cognition is associated with preschool children's PA behavior, and the results suggest that maternal social cognition may not affect children FV and ST behaviors. Further research is necessary to test the mediation of maternal social cognition on preschool children's ST behavior and the correlations between maternal social cognition and children's ST behavior.

  10. Mediation of the Physical Activity and Healthy Nutrition Behaviors of Preschool Children by Maternal Cognition in China

    PubMed Central

    Xu, Xianglong; Sharma, Manoj; Liu, Lingli; Hu, Ping; Zhao, Yong

    2016-01-01

    (1) Objective: We aimed to explore the role of social cognitive theory (SCT) of mothers in the physical activity and healthy nutrition behaviors of preschool children; (2) Methods: We used a self-administered five-point Likert common physical activity and nutrition behaviors scale in Chinese based on a social cognitive theory scale in English with established validity and reliability in the USA. The current study adopted the proportional sampling method to survey mothers of preschool children in four areas—namely, Chongqing, Chengdu, Taiyuan, and Shijiazhuang—of China; (3) Results: We included 1208 mothers (80.0% mothers of normal weight children, age 31.87 ± 4.19 years). Positive correlations were found between maternal social cognition and preschool children’s physical activity (PA) behavior (p < 0.0001). However, an insignificant correlation is observed between preschool children’s fruits and vegetables (FV) behavior, screen time (ST) behavior, and maternal social cognition; (4) Conclusions: This study provides some implications for increasing fruit and vegetable consumption, increasing physical activity time, and reducing screen time in preschool children using SCT in China. Maternal social cognition is associated with preschool children’s PA behavior, and the results suggest that maternal social cognition may not affect children FV and ST behaviors. Further research is necessary to test the mediation of maternal social cognition on preschool children’s ST behavior and the correlations between maternal social cognition and children’s ST behavior. PMID:27649215

  11. Sex-dependent changes in brain CB1R expression and functionality and immune CB2R expression as a consequence of maternal deprivation and adolescent cocaine exposure.

    PubMed

    Llorente-Berzal, Alvaro; Assis, María A; Rubino, Tiziana; Zamberletti, Erica; Marco, Eva M; Parolaro, Daniela; Ambrosio, Emilio; Viveros, María-Paz

    2013-08-01

    Early life stress has been associated with several psychiatric disorders, including drug addiction. Actually, maternal deprivation (MD) alters the endocannabinoid system, which participates in motivation and reward for drugs, including cocaine. At youth, the rate of cocaine abuse is alarmingly increasing. Herein, we have investigated the consequences of MD and/or adolescent cocaine exposure in brain CB1Rs and CB2Rs in immune tissues. Control and maternally deprived (24h on postnatal day, pnd, 9) male and female Wistar rats were administered cocaine (8mg/kg/day) or saline during adolescence (pnd 28-42). At adulthood, [(3)H]-CP-55,940 autoradiographic binding was employed for the analysis of CB1R density and CP-55,940-stimulated [(35)S]-GTPgammaS binding for CB1R functionality; CB2R expression was analyzed by Western blotting. Sex differences in CB1R expression and functionality were found, and MD induced important and enduring sex-dependent changes. In addition, the plastic changes induced by adolescent cocaine administration in brain CB1Rs were differentially influenced by early life events. MD increased spleen CB2R expression while adolescent cocaine administration attenuated this effect; cocaine exposure also diminished CB2R expression in bone marrow. Present findings provide evidence for changes in brain CB1R expression and functionality and immune CB2R expression as a consequence of early life stress and adolescent cocaine exposure, and indicate functional interactions between both treatments, which in many regions differ between males and females.

  12. Sex-dependent changes in brain CB1R expression and functionality and immune CB2R expression as a consequence of maternal deprivation and adolescent cocaine exposure.

    PubMed

    Llorente-Berzal, Alvaro; Assis, María A; Rubino, Tiziana; Zamberletti, Erica; Marco, Eva M; Parolaro, Daniela; Ambrosio, Emilio; Viveros, María-Paz

    2013-08-01

    Early life stress has been associated with several psychiatric disorders, including drug addiction. Actually, maternal deprivation (MD) alters the endocannabinoid system, which participates in motivation and reward for drugs, including cocaine. At youth, the rate of cocaine abuse is alarmingly increasing. Herein, we have investigated the consequences of MD and/or adolescent cocaine exposure in brain CB1Rs and CB2Rs in immune tissues. Control and maternally deprived (24h on postnatal day, pnd, 9) male and female Wistar rats were administered cocaine (8mg/kg/day) or saline during adolescence (pnd 28-42). At adulthood, [(3)H]-CP-55,940 autoradiographic binding was employed for the analysis of CB1R density and CP-55,940-stimulated [(35)S]-GTPgammaS binding for CB1R functionality; CB2R expression was analyzed by Western blotting. Sex differences in CB1R expression and functionality were found, and MD induced important and enduring sex-dependent changes. In addition, the plastic changes induced by adolescent cocaine administration in brain CB1Rs were differentially influenced by early life events. MD increased spleen CB2R expression while adolescent cocaine administration attenuated this effect; cocaine exposure also diminished CB2R expression in bone marrow. Present findings provide evidence for changes in brain CB1R expression and functionality and immune CB2R expression as a consequence of early life stress and adolescent cocaine exposure, and indicate functional interactions between both treatments, which in many regions differ between males and females. PMID:23680694

  13. The effect of maternal immunization on female oxidative status, yolk antioxidants and offspring survival in a songbird.

    PubMed

    Casasole, G; Costantini, D; Cichoń, M; Rutkowska, J

    2016-04-01

    Immune defense involves inflammatory reactions in which immune cells produce reactive oxygen species (ROS) to fight pathogens. ROS may however cause damage to the host if they are not balanced by antioxidant defenses. Therefore, one should expect individuals undergoing an immune reaction to use antioxidants to prevent oxidative stress. Antioxidants are vital compounds that provide important protection against oxidative damage of embryos and newly hatched chicks. Thus, during egg laying a female that contracted an infection may face a trade-off between the allocation of antioxidants into self-maintenance and into her offspring via the eggs. In our study we investigated whether immunized females face this trade-off and consequently modify the antioxidant allocation into the eggs and whether this allocation affects offspring performance. We injected female zebra finches (Taeniopygia guttata) with lipopolysaccharide prior to egg laying while some females were left unimmunized. We removed the second egg of each clutch, while we allowed the other eggs to hatch. We assessed oxidative stress in females 24h after immunization, yolk antioxidant capacity of the second egg of the clutch and survival success of the offspring until adulthood. Compared to controls, immunized females had higher oxidative damage, but similar plasma non-enzymatic antioxidant levels. The treatment did not affect yolk antioxidants, clutch size, laying date and offspring survival. However, we found a positive correlation between yolk antioxidant capacity and offspring survival, irrespective of the treatment. Our study suggests that our immune challenge may not have changed female strategy of antioxidant allocation between self-maintenance and offspring survival.

  14. Large-scale field trials of active immunizing agents

    PubMed Central

    Cockburn, W. Charles

    1955-01-01

    In this discussion of the methods to be used in large-scale field trials of active immunizing agents and of the results to be expected from such trials, special emphasis is laid on pertussis vaccine trials in Great Britain. After a review of the criteria for strictly controlled field studies and of the investigation of typhoid vaccines conducted in 1904-08 by the Antityphoid Committee of the British Army, the author describes the pertussis vaccine studies which have been and are now being carried by the Whooping-Cough Immunization Committee of the Medical Research Council of Great Britain. The original strictly controlled trials have been completed and the results published. Studies are now being made of vaccines prepared by different methods and evaluated both in the field and in the laboratory. Each vaccine is given to some 2000-3000 children of 4-6 months to 4 years of age. By the end of the studies 30 000-40 000 children will have been followed up for a period of two years. Since in the current studies all the children are vaccinated and none are left as unvaccinated controls, the relative and not the absolute protective value of the vaccines will be measured. PMID:13270079

  15. GITR Activation Positively Regulates Immune Responses against Toxoplasma gondii

    PubMed Central

    Costa, Frederico R. C.; Mota, Caroline M.; Santiago, Fernanda M.; Silva, Murilo V.; Ferreira, Marcela D.; Fonseca, Denise M.; Silva, João S.; Mineo, José R.; Mineo, Tiago W. P.

    2016-01-01

    Toxoplasma gondii is a widespread parasite responsible for causing clinical diseases especially in pregnant and immunosuppressed individuals. Glucocorticoid-induced TNF receptor (GITR), which is also known as TNFRS18 and belongs to the TNF receptor superfamily, is found to be expressed in various cell types of the immune system and provides an important costimulatory signal for T cells and myeloid cells. However, the precise role of this receptor in the context of T. gondii infection remains elusive. Therefore, the current study investigated the role of GITR activation in the immunoregulation mechanisms induced during the experimental infection of mice with T. gondii. Our data show that T. gondii infection slightly upregulates GITR expression in Treg cells and B cells, but the most robust increment in expression was observed in macrophages and dendritic cells. Interestingly, mice infected and treated with an agonistic antibody anti-GITR (DTA-1) presented a robust increase in pro-inflammatory cytokine production at preferential sites of parasite replication, which was associated with the decrease in latent brain parasitism of mice under treatment with DTA-1. Several in vivo and in vitro analysis were performed to identify the cellular mechanisms involved in GITR activation upon infection, however no clear alterations were detected in the phenotype/function of macrophages, Tregs and B cells under treatment with DTA-1. Therefore, GITR appears as a potential target for intervention during infection by the parasite Toxoplasma gondii, even though further studies are still necessary to better characterize the immune response triggered by GITR activation during T. gondii infection. PMID:27027302

  16. Lessons in community health activism: the maternity care coalition, 1970-1990.

    PubMed

    Maldonado, Linda

    2014-01-01

    This study employed historical methodologies to explore the means through which the Maternity Care Coalition used grassroots activism to dismantle the power structures and other obstacles that contributed to high infant mortality rates in Philadelphia's health districts 5 and 6 during the 1980s. Infant mortality within the black community has been a persistent phenomenon in the United States. Refusing to accept poverty as a major determinant of infant mortality within marginalized populations of women, activists during the 1980s harnessed momentum from a postcivil rights context and sought alternative methods toward change and improvement of infant mortality rates. PMID:24892861

  17. [Significance of the functional activity of antibodies in influenza immunity].

    PubMed

    Naĭkhin, A N; Artem'eva, S A; Bosak, L V; Katorgina, L G

    1995-01-01

    A simple and inexpensive test for mass examination of the functional activity of serum antibodies was developed. The test is based on a kinetic serologic reaction that reflects the time course of changes in antibody titers depending on the time of contact of the tested material with antigen. The curves of serum kinetic titration were processed on a computer by the special programme. As a result, an integral factor, an antibody functional activity index (AFAI) was calculated for each serum sample under study. The titers and AFAI were determined in more than 2,000 healthy persons, patients with influenza A and B, and those immunized with different influenza vaccines. The persons having similar antibody titers were demonstrated to greatly differ in AFAI. The functional activity of antibodies is a more precise marker of protection from influenza than the routine quantitative characteristics of antibodies, i.e. titers. The high baseline AFAI decreased the severity of influenza infection. Live influenza vaccines stimulated the production of antibodies having higher AFAI than inactivated ones. The live influenza strains (candidates for vaccine ones) significantly differed in their ability to stimulate the production of antibodies having a high functional activity.

  18. Association between maternal education and objectively measured physical activity and sedentary time in adolescents

    PubMed Central

    Sherar, Lauren B; Griffin, Tom P; Ekelund, Ulf; Cooper, Ashley R; Esliger, Dale W; van Sluijs, Esther M F; Bo Andersen, Lars; Cardon, Greet; Davey, Rachel; Froberg, Karsten; Hallal, Pedro C; Janz, Kathleen F; Kordas, Katarzyna; Kriemler, Susi; Pate, Russell R; Puder, Jardena J; Sardinha, Luis B; Timperio, Anna F; Page, Angie S

    2016-01-01

    Background Investigating socioeconomic variation in physical activity (PA) and sedentary time is important as it may represent a pathway by which socioeconomic position (SEP) leads to ill health. Findings on the association between children's SEP and objectively assessed PA and/or sedentary time are mixed, and few studies have included international samples. Objective Examine the associations between maternal education and adolescent's objectively assessed PA and sedentary time. Methods This is an observational study of 12 770 adolescents (10–18 years) pooled from 10 studies from Europe, Australia, Brazil and the USA. Original PA data were collected between 1997 and 2009. The associations between maternal education and accelerometer variables were examined using robust multivariable regression, adjusted for a priori confounders (ie, body mass index, monitor wear time, season, age and sex) and regression coefficients combined across studies using random effects meta-analyses. Analyses were conducted in March 2014. Results Adolescents of university educated mothers spent more time sedentary (9.5 min/day, p=0.005) and less time in light activity (10 min/day, p<0.001) compared with adolescents of high school educated mothers. Pooled analysis across two studies from Brazil and Portugal (analysed separately because of the different coding of maternal education) showed that children of higher educated mothers (tertiary vs primary/secondary) spent less time in moderate to vigorous PA (MVPA) (6.6 min/day, p=0.001) and in light PA (39.2 min/day: p<0.001), and more time sedentary (45.9 min/day, p<0.001). Conclusions Across a number of international samples, adolescents of mothers with lower education may not be at a disadvantage in terms of overall objectively measured PA. PMID:26802168

  19. Mouse early extra-embryonic lineages activate compensatory endocytosis in response to poor maternal nutrition.

    PubMed

    Sun, Congshan; Velazquez, Miguel A; Marfy-Smith, Stephanie; Sheth, Bhavwanti; Cox, Andy; Johnston, David A; Smyth, Neil; Fleming, Tom P

    2014-03-01

    Mammalian extra-embryonic lineages perform the crucial role of nutrient provision during gestation to support embryonic and fetal growth. These lineages derive from outer trophectoderm (TE) and internal primitive endoderm (PE) in the blastocyst and subsequently give rise to chorio-allantoic and visceral yolk sac placentae, respectively. We have shown maternal low protein diet exclusively during mouse preimplantation development (Emb-LPD) is sufficient to cause a compensatory increase in fetal and perinatal growth that correlates positively with increased adult-onset cardiovascular, metabolic and behavioural disease. Here, to investigate early mechanisms of compensatory nutrient provision, we assessed the influence of maternal Emb-LPD on endocytosis within extra-embryonic lineages using quantitative imaging and expression of markers and proteins involved. Blastocysts collected from Emb-LPD mothers within standard culture medium displayed enhanced TE endocytosis compared with embryos from control mothers with respect to the number and collective volume per cell of vesicles with endocytosed ligand and fluid and lysosomes, plus protein expression of megalin (Lrp2) LDL-family receptor. Endocytosis was also stimulated using similar criteria in the outer PE-like lineage of embryoid bodies formed from embryonic stem cell lines generated from Emb-LPD blastocysts. Using an in vitro model replicating the depleted amino acid (AA) composition found within the Emb-LPD uterine luminal fluid, we show TE endocytosis response is activated through reduced branched-chain AAs (leucine, isoleucine, valine). Moreover, activation appears mediated through RhoA GTPase signalling. Our data indicate early embryos regulate and stabilise endocytosis as a mechanism to compensate for poor maternal nutrient provision.

  20. The effect of a maternal dietary yeast cell wall supplement during gestation on cow performance and calf growth and immunity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to determine if feeding of yeast cell wall (YCW) to pregnant cows influences cow performance as well as postnatal calf growth and immunity. Multiparous cows were grouped by predicted calving date into groups of control (C; n=24) and supplemented (Y; n=24) cows. The Y ...

  1. Prenatal immune activation in mice blocks the effects of environmental enrichment on exploratory behavior and microglia density.

    PubMed

    Buschert, Jens; Sakalem, Marna E; Saffari, Roja; Hohoff, Christa; Rothermundt, Matthias; Arolt, Volker; Zhang, Weiqi; Ambrée, Oliver

    2016-06-01

    Adverse environmental factors including prenatal maternal infection are capable of inducing long-lasting behavioral and neural alterations which can enhance the risk to develop schizophrenia. It is so far not clear whether supportive postnatal environments are able to modify such prenatally-induced alterations. In rodent models, environmental enrichment influences behavior and cognition, for instance by affecting endocrinologic, immunologic, and neuroplastic parameters. The current study was designed to elucidate the influence of postnatal environmental enrichment on schizophrenia-like behavioral alterations induced by prenatal polyI:C immune stimulation at gestational day 9 in mice. Adult offspring were tested for amphetamine-induced locomotion, social interaction, and problem-solving behavior as well as expression of dopamine D1 and D2 receptors and associated molecules, microglia density and adult neurogenesis. Prenatal polyI:C treatment resulted in increased dopamine sensitivity and dopamine D2 receptor expression in adult offspring which was not reversed by environmental enrichment. Prenatal immune activation prevented the effects of environmental enrichment which increased exploratory behavior and microglia density in NaCl treated mice. Problem-solving behavior as well as the number of immature neurons was affected by neither prenatal immune stimulation nor postnatal environmental enrichment. The behavioral and neural alterations that persist into adulthood could not generally be modified by environmental enrichment. This might be due to early neurodevelopmental disturbances which could not be rescued or compensated for at a later developmental stage.

  2. Hormone activities and the cell cycle machinery in immunity-triggered growth inhibition.

    PubMed

    Reitz, M U; Gifford, M L; Schäfer, P

    2015-04-01

    Biotic stress and diseases caused by pathogen attack pose threats in crop production and significantly reduce crop yields. Enhancing immunity against pathogens is therefore of outstanding importance in crop breeding. However, this must be balanced, as immune activation inhibits plant growth. This immunity-coupled growth trade-off does not support resistance but is postulated to reflect the reallocation of resources to drive immunity. There is, however, increasing evidence that growth-immunity trade-offs are based on the reconfiguration of hormone pathways, shared by growth and immunity signalling. Studies in roots revealed the role of hormones in orchestrating growth across different cell types, with some hormones showing a defined cell type-specific activity. This is apparently highly relevant for the regulation of the cell cycle machinery and might be part of the growth-immunity cross-talk. Since plants are constantly exposed to Immuno-activating microbes under agricultural conditions, the transition from a growth to an immunity operating mode can significantly reduce crop yield and can conflict our efforts to generate next-generation crops with improved yield under climate change conditions. By focusing on roots, we outline the current knowledge of hormone signalling on the cell cycle machinery to explain growth trade-offs induced by immunity. By referring to abiotic stress studies, we further introduce how root cell type-specific hormone activities might contribute to growth under immunity and discuss the feasibility of uncoupling the growth-immunity cross-talk.

  3. Hormone activities and the cell cycle machinery in immunity-triggered growth inhibition

    PubMed Central

    Reitz, M. U.; Gifford, M. L.; Schäfer, P.

    2015-01-01

    Biotic stress and diseases caused by pathogen attack pose threats in crop production and significantly reduce crop yields. Enhancing immunity against pathogens is therefore of outstanding importance in crop breeding. However, this must be balanced, as immune activation inhibits plant growth. This immunity-coupled growth trade-off does not support resistance but is postulated to reflect the reallocation of resources to drive immunity. There is, however, increasing evidence that growth–immunity trade-offs are based on the reconfiguration of hormone pathways, shared by growth and immunity signalling. Studies in roots revealed the role of hormones in orchestrating growth across different cell types, with some hormones showing a defined cell type-specific activity. This is apparently highly relevant for the regulation of the cell cycle machinery and might be part of the growth–immunity cross-talk. Since plants are constantly exposed to Immuno-activating microbes under agricultural conditions, the transition from a growth to an immunity operating mode can significantly reduce crop yield and can conflict our efforts to generate next-generation crops with improved yield under climate change conditions. By focusing on roots, we outline the current knowledge of hormone signalling on the cell cycle machinery to explain growth trade-offs induced by immunity. By referring to abiotic stress studies, we further introduce how root cell type-specific hormone activities might contribute to growth under immunity and discuss the feasibility of uncoupling the growth–immunity cross-talk. PMID:25821072

  4. Mechanisms and pathways of innate immune activation and regulation in health and cancer

    PubMed Central

    Cui, Jun; Chen, Yongjun; Wang, Helen Y; Wang, Rong-Fu

    2015-01-01

    Research on innate immune signaling and regulation has recently focused on pathogen recognition receptors (PRRs) and their signaling pathways. Members of PRRs sense diverse microbial invasions or danger signals, and initiate innate immune signaling pathways, leading to proinflammatory cytokines production, which, in turn, instructs adaptive immune response development. Despite the diverse functions employed by innate immune signaling to respond to a variety of different pathogens, the innate immune response must be tightly regulated. Otherwise, aberrant, uncontrolled immune responses will lead to harmful, or even fatal, consequences. Therefore, it is essential to better discern innate immune signaling and many regulators, controlling various signaling pathways, have been identified. In this review, we focus on the recent advances in our understanding of the activation and regulation of innate immune signaling in the host response to pathogens and cancer. PMID:25625930

  5. Muscles provide protection during microbial infection by activating innate immune response pathways in Drosophila and zebrafish

    PubMed Central

    Chatterjee, Arunita; Roy, Debasish; Patnaik, Esha

    2016-01-01

    ABSTRACT Muscle contraction brings about movement and locomotion in animals. However, muscles have also been implicated in several atypical physiological processes including immune response. The role of muscles in immunity and the mechanism involved has not yet been deciphered. In this paper, using Drosophila indirect flight muscles (IFMs) as a model, we show that muscles are immune-responsive tissues. Flies with defective IFMs are incapable of mounting a potent humoral immune response. Upon immune challenge, the IFMs produce anti-microbial peptides (AMPs) through the activation of canonical signaling pathways, and these IFM-synthesized AMPs are essential for survival upon infection. The trunk muscles of zebrafish, a vertebrate model system, also possess the capacity to mount an immune response against bacterial infections, thus establishing that immune responsiveness of muscles is evolutionarily conserved. Our results suggest that physiologically fit muscles might boost the innate immune response of an individual. PMID:27101844

  6. Mucosal Regulatory T Cells and T Helper 17 Cells in HIV-Associated Immune Activation

    PubMed Central

    Pandiyan, Pushpa; Younes, Souheil-Antoine; Ribeiro, Susan Pereira; Talla, Aarthi; McDonald, David; Bhaskaran, Natarajan; Levine, Alan D.; Weinberg, Aaron; Sekaly, Rafick P.

    2016-01-01

    Residual mucosal inflammation along with chronic systemic immune activation is an important feature in individuals infected with human immunodeficiency virus (HIV), and has been linked to a wide range of co-morbidities, including malignancy, opportunistic infections, immunopathology, and cardiovascular complications. Although combined antiretroviral therapy (cART) can reduce plasma viral loads to undetectable levels, reservoirs of virus persist, and increased mortality is associated with immune dysbiosis in mucosal lymphoid tissues. Immune-based therapies are pursued with the goal of improving CD4+ T-cell restoration, as well as reducing chronic immune activation in cART-treated patients. However, the majority of research on immune activation has been derived from analysis of circulating T cells. How immune cell alterations in mucosal tissues contribute to HIV immune dysregulation and the associated risk of non-infectious chronic complications is less studied. Given the significant differences between mucosal T cells and circulating T cells, and the immediate interactions of mucosal T cells with the microbiome, more attention should be devoted to mucosal immune cells and their contribution to systemic immune activation in HIV-infected individuals. Here, we will focus on mucosal immune cells with a specific emphasis on CD4+ T lymphocytes, such as T helper 17 cells and CD4+Foxp3+ regulatory T cells (Tregs), which play crucial roles in maintaining mucosal barrier integrity and preventing inflammation, respectively. We hypothesize that pro-inflammatory milieu in cART-treated patients with immune activation significantly contributes to enhanced loss of Th17 cells and increased frequency of dysregulated Tregs in the mucosa, which in turn may exacerbate immune dysfunction in HIV-infected patients. We also present initial evidence to support this hypothesis. A better comprehension of how pro-inflammatory milieu impacts these two types of cells in the mucosa will shed light

  7. Effect of maternal anti-HPA-1a antibodies and polyclonal IVIG on the activation status of vascular endothelial cells

    PubMed Central

    RADDER, C M; BEEKHUIZEN, H; KANHAI, H H H; BRAND, A

    2004-01-01

    Maternal anti-HPA-1a antibodies can cause severe fetal and neonatal alloimmune thrombocytopenia (FNAIT), complicated by intracranial haemorrhage (ICH). Antenatal treatment with maternal intravenous immunoglobulin (IVIG) seems to protect against ICH even when thrombocytopenia persists. The aim of this study was to investigate if anti-HPA-1a antibodies and IVIG potentially affect vascular endothelial cells (ECs) in order to identify susceptibility for ICH. Human umbilical cord endothelial cells (HUVEC) were incubated with anti-HPA-1a antibodies with or without polyclonal IVIG and evaluated for EC activation. Maternal sera with anti-HPA-1a antibodies affected neither the EC expression of intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) and tissue factor (TF) nor the release of van Willebrand factor (vWF) or interleukin (IL)-8 nor the integrity of ECs. Maternal sera obtained after IVIG treatment and polyclonal IVIG decrease constitutive and cytokine-induced ICAM-1 and VCAM-1 expression on ECs. The results show that maternal anti-HPA-1a antibodies cause no activation or damage of ECs in this model. The clinical relevance of the de-activating properties of IVIG on EC activation with respect to ICH deserves further investigation. PMID:15196265

  8. Immune-suppressive activity of punicalagin via inhibition of NFAT activation

    SciTech Connect

    Lee, Sang-Ik; Kim, Byoung-Soo; Kim, Kyoung-Shin; Lee, Samkeun; Shin, Kwang-Soo; Lim, Jong-Soon

    2008-07-11

    Since T cell activation is central to the development of autoimmune diseases, we screened a natural product library comprising 1400 samples of medicinal herbal extracts, to identify compounds that suppress T cell activity. Punicalagin (PCG) isolated from the fruit of Punica granatum was identified as a potent immune suppressant, based on its inhibitory action on the activation of the nuclear factor of activated T cells (NFAT). PCG downregulated the mRNA and soluble protein expression of interleukin-2 from anti-CD3/anti-CD28-stimulated murine splenic CD4+ T cells and suppressed mixed leukocytes reaction (MLR) without exhibiting cytotoxicity to the cells. In vivo, the PCG treatment inhibited phorbol 12-myristate 13-acetate (PMA)-induced chronic ear edema in mice and decreased CD3+ T cell infiltration of the inflamed tissue. These results suggest that PCG could be a potential candidate for the therapeutics of various immune pathologies.

  9. Metabolic Pathways In Immune Cell Activation And Quiescence

    PubMed Central

    Pearce, Erika L.; Pearce, Edward J.

    2013-01-01

    Studies of immune system metabolism (“immunometabolism”) segregate along two paths. The first investigates the effects of immune cells on organs that regulate whole body metabolism, such as adipose tissue and liver. The second explores the role of metabolic pathways within immune cells and how this regulates immune response outcome. Distinct metabolic pathways diverge and converge at many levels and cells therefore face choices in how to achieve their metabolic goals. There is interest in fully understanding how and why immune cells commit to particular metabolic fates, and in elucidating the immunologic consequences of reaching a metabolic endpoint by one pathway versus another. This is particularly intriguing since metabolic commitment is influenced not only by substrate availability, but also by signaling pathways elicited by metabolites. Thus metabolic choices in cells enforce fate and function and this area will be the subject of this review. PMID:23601682

  10. Immune activation affects chemical sexual ornaments of male Iberian wall lizards

    NASA Astrophysics Data System (ADS)

    López, Pilar; Gabirot, Marianne; Martín, José

    2009-01-01

    Many animals use chemical signals in sexual selection, but it is not clear how these sexual traits might have evolved to signal honestly male condition. It is possible that there is a trade-off between maintaining the immune system and the elaboration of ornaments. We experimentally challenged the immune system of male Iberian wall lizards, Podarcis hispanica, with a bacterial antigen (lipopolysaccharide), without pathogenic effects, to explore whether the immune activation affected chemical ornaments. Immune activation resulted in decreased proportions of a major chemical in femoral secretions (cholesta-5,7-dien-3-ol = provitamin D3) known to be selected in scent of males by females and which active form (vitamin D) has a variety of important effects on immune system function. This result suggests the existence of a potential trade-off between physiological regulation of the immune system and the allocation of essential nutrients (vitamins) to sexual chemical ornaments in male lizards.

  11. Non-genetic inheritable potential of maternal antibodies.

    PubMed

    Lemke, Hilmar; Hansen, Hinrich; Lange, Hans

    2003-07-28

    Maternal antibodies (IgG and IgA) not only provide passive protection against microbial infections, but also exert a variety of equally important active, idiotypically-mediated immunoregulatory functions. Since the generation of maternal antibodies depends entirely on the stimulation of the mother's immune system by external mainly thymus-dependent antigens, with long-lived antigen independent plasma cells in the bone marrow, maternal antibodies represent the mother's collective ontogenetic immunological experience. Although their stimulatory potential in mice is restricted to the neonatal imprinting period, maternal antibodies exert a life-long determinative influence which is even dominant over seemingly genetic predispositions. Therefore, the functional impact of maternal IgG antibodies appears phenotypically as a non-genetic inheritance.

  12. The Split Virus Influenza Vaccine rapidly activates immune cells through Fcγ receptors.

    PubMed

    O'Gorman, William E; Huang, Huang; Wei, Yu-Ling; Davis, Kara L; Leipold, Michael D; Bendall, Sean C; Kidd, Brian A; Dekker, Cornelia L; Maecker, Holden T; Chien, Yueh-Hsiu; Davis, Mark M

    2014-10-14

    Seasonal influenza vaccination is one of the most common medical procedures and yet the extent to which it activates the immune system beyond inducing antibody production is not well understood. In the United States, the most prevalent formulations of the vaccine consist of degraded or "split" viral particles distributed without any adjuvants. Based on previous reports we sought to determine whether the split influenza vaccine activates innate immune receptors-specifically Toll-like receptors. High-dimensional proteomic profiling of human whole-blood using Cytometry by Time-of-Flight (CyTOF) was used to compare signaling pathway activation and cytokine production between the split influenza vaccine and a prototypical TLR response ex vivo. This analysis revealed that the split vaccine rapidly and potently activates multiple immune cell types but yields a proteomic signature quite distinct from TLR activation. Importantly, vaccine induced activity was dependent upon the presence of human sera indicating that a serum factor was necessary for vaccine-dependent immune activation. We found this serum factor to be human antibodies specific for influenza proteins and therefore immediate immune activation by the split vaccine is immune-complex dependent. These studies demonstrate that influenza virus "splitting" inactivates any potential adjuvants endogenous to influenza, such as RNA, but in previously exposed individuals can elicit a potent immune response by facilitating the rapid formation of immune complexes. PMID:25203448

  13. The Split Virus Influenza Vaccine rapidly activates immune cells through Fcγ Receptors

    PubMed Central

    O’Gorman, William E.; Huang, Huang; Wei, Yu-Ling; Davis, Kara L.; Leipold, Michael D.; Bendall, Sean C.; Kidd, Brian A.; Dekker, Cornelia L.; Maecker, Holden T.; Chien, Yueh-Hsiu; Davis, Mark M.

    2014-01-01

    Seasonal influenza vaccination is one of the most common medical procedures and yet the extent to which it activates the immune system beyond inducing antibody production is not well understood. In the United States, the most prevalent formulations of the vaccine consist of degraded or “split” viral particles distributed without any adjuvants. Based on previous reports we sought to determine whether the split influenza vaccine activates innate immune receptors—specifically Toll-like receptors. High-dimensional proteomic profiling of human whole-blood using Cytometry by Time-of-Flight (CyTOF) was used to compare signaling pathway activation and cytokine production between the split influenza vaccine and a prototypical TLR response ex vivo. This analysis revealed that the split vaccine rapidly and potently activates multiple immune cell types but yields a proteomic signature quite distinct from TLR activation. Importantly, vaccine induced activity was dependent upon the presence of human sera indicating that a serum factor was necessary for vaccine-dependent immune activation. We found this serum factor to be human antibodies specific for influenza proteins and therefore immediate immune activation by the split vaccine is immune-complex dependent. These studies demonstrate that influenza virus “splitting” inactivates any potential adjuvants endogenous to influenza, such as RNA, but in previously exposed individuals can elicit a potent immune response by facilitating the rapid formation of immune complexes. PMID:25203448

  14. The interplay of early-life stress, nutrition, and immune activation programs adult hippocampal structure and function

    PubMed Central

    Hoeijmakers, Lianne; Lucassen, Paul J.; Korosi, Aniko

    2015-01-01

    Early-life adversity increases the vulnerability to develop psychopathologies and cognitive decline later in life. This association is supported by clinical and preclinical studies. Remarkably, experiences of stress during this sensitive period, in the form of abuse or neglect but also early malnutrition or an early immune challenge elicit very similar long-term effects on brain structure and function. During early-life, both exogenous factors like nutrition and maternal care, as well as endogenous modulators, including stress hormones and mediator of immunological activity affect brain development. The interplay of these key elements and their underlying molecular mechanisms are not fully understood. We discuss here the hypothesis that exposure to early-life adversity (specifically stress, under/malnutrition and infection) leads to life-long alterations in hippocampal-related cognitive functions, at least partly via changes in hippocampal neurogenesis. We further discuss how these different key elements of the early-life environment interact and affect one another and suggest that it is a synergistic action of these elements that shapes cognition throughout life. Finally, we consider different intervention studies aiming to prevent these early-life adversity induced consequences. The emerging evidence for the intriguing interplay of stress, nutrition, and immune activity in the early-life programming calls for a more in depth understanding of the interaction of these elements and the underlying mechanisms. This knowledge will help to develop intervention strategies that will converge on a more complete set of changes induced by early-life adversity. PMID:25620909

  15. The interplay of early-life stress, nutrition, and immune activation programs adult hippocampal structure and function.

    PubMed

    Hoeijmakers, Lianne; Lucassen, Paul J; Korosi, Aniko

    2014-01-01

    Early-life adversity increases the vulnerability to develop psychopathologies and cognitive decline later in life. This association is supported by clinical and preclinical studies. Remarkably, experiences of stress during this sensitive period, in the form of abuse or neglect but also early malnutrition or an early immune challenge elicit very similar long-term effects on brain structure and function. During early-life, both exogenous factors like nutrition and maternal care, as well as endogenous modulators, including stress hormones and mediator of immunological activity affect brain development. The interplay of these key elements and their underlying molecular mechanisms are not fully understood. We discuss here the hypothesis that exposure to early-life adversity (specifically stress, under/malnutrition and infection) leads to life-long alterations in hippocampal-related cognitive functions, at least partly via changes in hippocampal neurogenesis. We further discuss how these different key elements of the early-life environment interact and affect one another and suggest that it is a synergistic action of these elements that shapes cognition throughout life. Finally, we consider different intervention studies aiming to prevent these early-life adversity induced consequences. The emerging evidence for the intriguing interplay of stress, nutrition, and immune activity in the early-life programming calls for a more in depth understanding of the interaction of these elements and the underlying mechanisms. This knowledge will help to develop intervention strategies that will converge on a more complete set of changes induced by early-life adversity.

  16. Experimental verification and molecular basis of active immunization against fungal pathogens in termites

    PubMed Central

    Liu, Long; Li, Ganghua; Sun, Pengdong; Lei, Chaoliang; Huang, Qiuying

    2015-01-01

    Termites are constantly exposed to many pathogens when they nest and forage in the field, so they employ various immune strategies to defend against pathogenic infections. Here, we demonstrate that the subterranean termite Reticulitermes chinensis employs active immunization to defend against the entomopathogen Metarhizium anisopliae. Our results showed that allogrooming frequency increased significantly between fungus-treated termites and their nestmates. Through active social contact, previously healthy nestmates only received small numbers of conidia from fungus-treated individuals. These nestmates experienced low-level fungal infections, resulting in low mortality and apparently improved antifungal defences. Moreover, infected nestmates promoted the activity of two antioxidant enzymes (SOD and CAT) and upregulated the expression of three immune genes (phenoloxidase, transferrin, and termicin). We found 20 differentially expressed proteins associated with active immunization in R. chinensis through iTRAQ proteomics, including 12 stress response proteins, six immune signalling proteins, and two immune effector molecules. Subsequently, two significantly upregulated (60S ribosomal protein L23 and isocitrate dehydrogenase) and three significantly downregulated (glutathione S-transferase D1, cuticle protein 19, and ubiquitin conjugating enzyme) candidate immune proteins were validated by MRM assays. These findings suggest that active immunization in termites may be regulated by different immune proteins. PMID:26458743

  17. Experimental verification and molecular basis of active immunization against fungal pathogens in termites.

    PubMed

    Liu, Long; Li, Ganghua; Sun, Pengdong; Lei, Chaoliang; Huang, Qiuying

    2015-10-13

    Termites are constantly exposed to many pathogens when they nest and forage in the field, so they employ various immune strategies to defend against pathogenic infections. Here, we demonstrate that the subterranean termite Reticulitermes chinensis employs active immunization to defend against the entomopathogen Metarhizium anisopliae. Our results showed that allogrooming frequency increased significantly between fungus-treated termites and their nestmates. Through active social contact, previously healthy nestmates only received small numbers of conidia from fungus-treated individuals. These nestmates experienced low-level fungal infections, resulting in low mortality and apparently improved antifungal defences. Moreover, infected nestmates promoted the activity of two antioxidant enzymes (SOD and CAT) and upregulated the expression of three immune genes (phenoloxidase, transferrin, and termicin). We found 20 differentially expressed proteins associated with active immunization in R. chinensis through iTRAQ proteomics, including 12 stress response proteins, six immune signalling proteins, and two immune effector molecules. Subsequently, two significantly upregulated (60S ribosomal protein L23 and isocitrate dehydrogenase) and three significantly downregulated (glutathione S-transferase D1, cuticle protein 19, and ubiquitin conjugating enzyme) candidate immune proteins were validated by MRM assays. These findings suggest that active immunization in termites may be regulated by different immune proteins.

  18. Maternal influenza immunization and birth outcomes of stillbirth and spontaneous abortion: a systematic review and meta-analysis.

    PubMed

    Bratton, Kristin N; Wardle, Melissa T; Orenstein, Walter A; Omer, Saad B

    2015-03-01

    Despite strong evidence that maternal influenza vaccination during pregnancy is safe, uptake of influenza vaccination during pregnancy remains low. We identified studies that assessed outcomes of stillbirth or spontaneous abortion after administration of influenza vaccine during pregnancy. We conducted a literature search in November 2013 that yielded 447 total citations. After removal of duplicates and studies deemed not relevant based on the title and abstract, 36 records underwent a full text review and 7 studies were included in the final review. Where possible, adjusted results were included in the meta-analysis. Women in the influenza vaccine group had a lower likelihood of stillbirth (relative risk [RR], 0.73; 95% confidence interval [CI], .55-.96); this association was similar when restricted to the H1N1pdm09 vaccine (RR, 0.69; 95% CI, .53-.90). The pooled estimate for spontaneous abortion was not significant (RR, 0.91; 95% CI, .68-1.22). These analyses add to the evidence base for the safety of influenza vaccination in pregnancy.

  19. A possible second type of maternal-fetal immune interaction involved in both male and female homosexuality.

    PubMed

    Blanchard, Ray

    2012-12-01

    Recent research has found that the mothers of firstborn homosexual sons produce fewer subsequent offspring than do the mothers of firstborn heterosexual sons. It was hypothesized that a subset of mothers of firstborn homosexuals may be responsible for this finding. If there is a subset of mothers whose immune reactions cause their first male fetus to be homosexual and their subsequent fetuses to die, then their immune reactions should also cause their first male fetus to have a lower birth weight. This leads to the prediction that, within the population of firstborn homosexual men, those with no younger siblings should also tend to have lower birth weights. This prediction was tested using a previously published sample of 1,445 firstborn subjects: 929 heterosexual females, 47 homosexual females, 409 heterosexual males, and 60 homosexual males. The results showed that firstborn homosexuals with no younger siblings (i.e., only children) did have lower birth weights compared with all the other subjects, but the finding applied to firstborn lesbian women as well as firstborn gay men.

  20. Maternal and infant activity: Analytic approaches for the study of circadian rhythm.

    PubMed

    Thomas, Karen A; Burr, Robert L; Spieker, Susan

    2015-11-01

    The study of infant and mother circadian rhythm entails choice of instruments appropriate for use in the home environment as well as selection of analytic approach that characterizes circadian rhythm. While actigraphy monitoring suits the needs of home study, limited studies have examined mother and infant rhythm derived from actigraphy. Among this existing research a variety of analyses have been employed to characterize 24-h rhythm, reducing ability to evaluate and synthesize findings. Few studies have examined the correspondence of mother and infant circadian parameters for the most frequently cited approaches: cosinor, non-parametric circadian rhythm analysis (NPCRA), and autocorrelation function (ACF). The purpose of this research was to examine analytic approaches in the study of mother and infant circadian activity rhythm. Forty-three healthy mother and infant pairs were studied in the home environment over a 72h period at infant age 4, 8, and 12 weeks. Activity was recorded continuously using actigraphy monitors and mothers completed a diary. Parameters of circadian rhythm were generated from cosinor analysis, NPCRA, and ACF. The correlation among measures of rhythm center (cosinor mesor, NPCRA mid level), strength or fit of 24-h period (cosinor magnitude and R(2), NPCRA amplitude and relative amplitude (RA)), phase (cosinor acrophase, NPCRA M10 and L5 midpoint), and rhythm stability and variability (NPCRA interdaily stability (IS) and intradaily variability (IV), ACF) was assessed, and additionally the effect size (eta(2)) for change over time evaluated. Results suggest that cosinor analysis, NPCRA, and autocorrelation provide several comparable parameters of infant and maternal circadian rhythm center, fit, and phase. IS and IV were strongly correlated with the 24-h cycle fit. The circadian parameters analyzed offer separate insight into rhythm and differing effect size for the detection of change over time. Findings inform selection of analysis and

  1. Maternal and infant activity: Analytic approaches for the study of circadian rhythm.

    PubMed

    Thomas, Karen A; Burr, Robert L; Spieker, Susan

    2015-11-01

    The study of infant and mother circadian rhythm entails choice of instruments appropriate for use in the home environment as well as selection of analytic approach that characterizes circadian rhythm. While actigraphy monitoring suits the needs of home study, limited studies have examined mother and infant rhythm derived from actigraphy. Among this existing research a variety of analyses have been employed to characterize 24-h rhythm, reducing ability to evaluate and synthesize findings. Few studies have examined the correspondence of mother and infant circadian parameters for the most frequently cited approaches: cosinor, non-parametric circadian rhythm analysis (NPCRA), and autocorrelation function (ACF). The purpose of this research was to examine analytic approaches in the study of mother and infant circadian activity rhythm. Forty-three healthy mother and infant pairs were studied in the home environment over a 72h period at infant age 4, 8, and 12 weeks. Activity was recorded continuously using actigraphy monitors and mothers completed a diary. Parameters of circadian rhythm were generated from cosinor analysis, NPCRA, and ACF. The correlation among measures of rhythm center (cosinor mesor, NPCRA mid level), strength or fit of 24-h period (cosinor magnitude and R(2), NPCRA amplitude and relative amplitude (RA)), phase (cosinor acrophase, NPCRA M10 and L5 midpoint), and rhythm stability and variability (NPCRA interdaily stability (IS) and intradaily variability (IV), ACF) was assessed, and additionally the effect size (eta(2)) for change over time evaluated. Results suggest that cosinor analysis, NPCRA, and autocorrelation provide several comparable parameters of infant and maternal circadian rhythm center, fit, and phase. IS and IV were strongly correlated with the 24-h cycle fit. The circadian parameters analyzed offer separate insight into rhythm and differing effect size for the detection of change over time. Findings inform selection of analysis and

  2. Placental HSD2 Expression and Activity Is Unaffected by Maternal Protein Consumption or Gender in C57BL/6 Mice

    PubMed Central

    Garbrecht, Mark R.; Lamb, Fred S.

    2013-01-01

    The placenta acts as a physiological barrier, preventing the transfer of maternal glucocorticoids to the developing fetus. This is accomplished via the oxidation, and subsequent inactivation, of endogenous glucocorticoids by the 11-β hydroxysteroid dehydrogenase type 2 enzyme (HSD2). Maternal protein restriction during pregnancy has been shown to result in a decrease in placental HSD2 expression and fetal glucocorticoid overexposure, especially late in gestation, resulting in low birth weight and “fetal programming” of the offspring. This dietary intervention impairs fetal growth and cardiovascular function in adult C57BL/6 offspring, but the impact on placental HSD2 has not been defined. The goal of the current study was to examine the effects of a maternal low-protein diet (18% versus 9% protein) on placental HSD2 gene expression and enzyme activity in mice during late gestation. In contrast to previous studies in rats, a maternal low-protein diet did not affect HSD2 protein or enzyme activity levels in the placentas of C57BL/6 mice and this was irrespective of the gender of the offspring. These data suggest that the effects of maternal protein restriction on adult phenotypes in C57BL/6 mice depend upon a mechanism that may be independent of placental HSD2 or possibly occurs earlier in gestation. PMID:23781346

  3. Ventral Striatum Dopamine D2 Receptor Activity Inhibits Rat Pups’ Vocalization Response to Loss of Maternal Contact

    PubMed Central

    Muller, Jeff M.; Moore, Holly; Myers, Michael M.; Shair, Harry N.

    2010-01-01

    Most mammalian infants vocalize when isolated. The vocalization promotes caregiver proximity, which is critical to survival. If, before isolation, a rat pup has contact with its dam, its isolation vocalization rate is increased (maternal potentiation) relative to isolation preceded only by littermate contact. Prior work showed that systemic administration of a D2 receptor agonist blocks maternal potentiation at doses that do not alter baseline vocalization. In this study, infusion of quinpirole (2 µg/side) into the nucleus accumbens also blocks maternal potentiation. Infusion of the accumbens with the D2 antagonist raclopride (4 µg/side) prevents systemic quinpirole from blocking potentiation. Quinpirole infusion in the dorsal striatum did not affect maternal potentiation and infusion of raclopride in the dorsal striatum did not reverse the block of maternal potentiation by systemic quinpirole. Vocalization results after a second vehicle infusion on a given day are no different than the results following an initial vehicle infusion, so experimental design can not account for the effects of drug infusions. Because activity level was increased by both dorsal and ventral striatum infusions, activity level can not account for the results. PMID:18298255

  4. Therapeutic Immunization with HIV-1 Tat Reduces Immune Activation and Loss of Regulatory T-Cells and Improves Immune Function in Subjects on HAART

    PubMed Central

    Ensoli, Barbara; Bellino, Stefania; Tripiciano, Antonella; Longo, Olimpia; Francavilla, Vittorio; Marcotullio, Simone; Cafaro, Aurelio; Picconi, Orietta; Paniccia, Giovanni; Scoglio, Arianna; Arancio, Angela; Ariola, Cristina; Ruiz Alvarez, Maria J.; Campagna, Massimo; Scaramuzzi, Donato; Iori, Cristina; Esposito, Roberto; Mussini, Cristina; Ghinelli, Florio; Sighinolfi, Laura; Palamara, Guido; Latini, Alessandra; Angarano, Gioacchino; Ladisa, Nicoletta; Soscia, Fabrizio; Mercurio, Vito S.; Lazzarin, Adriano; Tambussi, Giuseppe; Visintini, Raffaele; Mazzotta, Francesco; Di Pietro, Massimo; Galli, Massimo; Rusconi, Stefano; Carosi, Giampiero; Torti, Carlo; Di Perri, Giovanni; Bonora, Stefano; Ensoli, Fabrizio; Garaci, Enrico

    2010-01-01

    Although HAART suppresses HIV replication, it is often unable to restore immune homeostasis. Consequently, non-AIDS-defining diseases are increasingly seen in treated individuals. This is attributed to persistent virus expression in reservoirs and to cell activation. Of note, in CD4+ T cells and monocyte-macrophages of virologically-suppressed individuals, there is continued expression of multi-spliced transcripts encoding HIV regulatory proteins. Among them, Tat is essential for virus gene expression and replication, either in primary infection or for virus reactivation during HAART, when Tat is expressed, released extracellularly and exerts, on both the virus and the immune system, effects that contribute to disease maintenance. Here we report results of an ad hoc exploratory interim analysis (up to 48 weeks) on 87 virologically-suppressed HAART-treated individuals enrolled in a phase II randomized open-label multicentric clinical trial of therapeutic immunization with Tat (ISS T-002). Eighty-eight virologically-suppressed HAART-treated individuals, enrolled in a parallel prospective observational study at the same sites (ISS OBS T-002), served for intergroup comparison. Immunization with Tat was safe, induced durable immune responses, and modified the pattern of CD4+ and CD8+ cellular activation (CD38 and HLA-DR) together with reduction of biochemical activation markers and persistent increases of regulatory T cells. This was accompanied by a progressive increment of CD4+ T cells and B cells with reduction of CD8+ T cells and NK cells, which were independent from the type of antiretroviral regimen. Increase in central and effector memory and reduction in terminally-differentiated effector memory CD4+ and CD8+ T cells were accompanied by increases of CD4+ and CD8+ T cell responses against Env and recall antigens. Of note, more immune-compromised individuals experienced greater therapeutic effects. In contrast, these changes were opposite, absent or partial in the

  5. Linalool exhibits cytotoxic effects by activating antitumor immunity.

    PubMed

    Chang, Mei-Yin; Shen, Yi-Ling

    2014-01-01

    According to recent studies, the Plantaginaceae, which are traditional Chinese herbal remedies, have potential for use in viral infection treatment and cancer therapy. Linalool and p-coumaric acid are two of the biologically active compounds that can be isolated from the Plantaginaceae. This study mainly focused on investigating the bioactivity of linalool as well as the bioactivity of p-coumaric acid in terms of their cytotoxic effects on cancer cells. Whether the mechanisms of such effects are generated through apoptosis and immunoregulatory activity were also investigated. By using WST-1 analysis, it was shown that linalool and p-coumaric acid have good inhibitory effects against breast, colorectal and liver cancer cells. The IC50 values of linalool for those cancer cell types were 224 μM, 222 μM, and 290 μM, respectively, and the IC50 values of p-coumaric acid were 693 μM, 215 μM and 87 μM, respectively. Cell cycle analysis also confirmed that linalool and p-coumaric acid can lead to apoptosis. By using flow cytometry, it was determined that treatment with linalool rather than p-coumaric acid significantly increased the sub-G1 phase and that there were more cells concentrated in the G1 phase. Furthermore, by using cytokine array analysis, we found that linalool can stimulate IFN-γ, IL-13, IL-2, IL-21, IL-21R, IL-4, IL-6sR and TNF-α secretion. This demonstrated that in addition to the bidirectional regulation capabilities found in linalool, it also induces Th1 cellular immune response in T-47D cells. These results showed that linalool holds great potential for use in cancer therapy, and we believe that it could provide an alternative way to take action against tumors.

  6. Immune activation caused by vascular oxidation promotes fibrosis and hypertension.

    PubMed

    Wu, Jing; Saleh, Mohamed A; Kirabo, Annet; Itani, Hana A; Montaniel, Kim Ramil C; Xiao, Liang; Chen, Wei; Mernaugh, Raymond L; Cai, Hua; Bernstein, Kenneth E; Goronzy, Jörg J; Weyand, Cornelia M; Curci, John A; Barbaro, Natalia R; Moreno, Heitor; Davies, Sean S; Roberts, L Jackson; Madhur, Meena S; Harrison, David G

    2016-01-01

    Vascular oxidative injury accompanies many common conditions associated with hypertension. In the present study, we employed mouse models with excessive vascular production of ROS (tg(sm/p22phox) mice, which overexpress the NADPH oxidase subunit p22(phox) in smooth muscle, and mice with vascular-specific deletion of extracellular SOD) and have shown that these animals develop vascular collagen deposition, aortic stiffening, renal dysfunction, and hypertension with age. T cells from tg(sm/p22phox) mice produced high levels of IL-17A and IFN-γ. Crossing tg(sm/p22phox) mice with lymphocyte-deficient Rag1(-/-) mice eliminated vascular inflammation, aortic stiffening, renal dysfunction, and hypertension; however, adoptive transfer of T cells restored these processes. Isoketal-protein adducts, which are immunogenic, were increased in aortas, DCs, and macrophages of tg(sm/p22phox) mice. Autologous pulsing with tg(sm/p22phox) aortic homogenates promoted DCs of tg(sm/p22phox) mice to stimulate T cell proliferation and production of IFN-γ, IL-17A, and TNF-α. Treatment with the superoxide scavenger tempol or the isoketal scavenger 2-hydroxybenzylamine (2-HOBA) normalized blood pressure; prevented vascular inflammation, aortic stiffening, and hypertension; and prevented DC and T cell activation. Moreover, in human aortas, the aortic content of isoketal adducts correlated with fibrosis and inflammation severity. Together, these results define a pathway linking vascular oxidant stress to immune activation and aortic stiffening and provide insight into the systemic inflammation encountered in common vascular diseases. PMID:26595812

  7. Antimycobacterial activity of Indigofera suffruticosa with activation potential of the innate immune system.

    PubMed

    de A Carli, Camila B; Quilles, Marcela B; Maia, Daniele C G; Lopes, Flávia C M; Santos, Rubens; Pavan, Fernando R; Fujimura Leite, Clarice Q; Calvo, Tamara R; Vilegas, Wagner; Carlos, Iracilda Z

    2010-08-01

    Mycobacterium tuberculosis is responsible for over 8 million cases of tuberculosis (TB) annually. Natural products may play important roles in the chemotherapy of TB. The antimycobacterial activity and the innate immune response of methanol (METH) and dichloromethane (DCM) extracts of Indigofera suffruticosa Miller (Fabaceae) were evaluated. We observed that the minimum inhibitory concentrations (MICs) for METH and DCM extracts were 125 and 1000 microg/mL, respectively. However, they were able to induce the innate immune response through the production of high levels of NO and TNF-alpha (p < 0.001) by peritoneal exudate cells (PECs). These results suggest that I. suffruticosa extracts may have an important immunological role in the control of TB once macrophage activity is induced by them.

  8. Placental cadmium as an additional noninvasive bioindicator of active maternal tobacco smoking.

    PubMed

    Piasek, Martina; Jurasović, Jasna; Sekovanić, Ankica; Brajenović, Nataša; Brčić Karačonji, Irena; Mikolić, Anja; Grgec, Antonija Sulimanec; Stasenko, Sandra

    2016-01-01

    Tobacco smoke (TS) is a mixture of chemicals that is known to exert carcinogenic and endocrine-disrupting effects, as well as adverse effects on various systems. In TS nicotine is the major alkaloid and cadmium (Cd) the most abundant metal ion. The aim of this investigation was to assess exposure to Cd attributed to TS in healthy postpartum subjects (mean age 28 years) after term vaginal delivery in a clinical hospital by determining metal levels in maternal blood, placenta, and cord blood in relation to nicotine in maternal hair (12-cm-long samples). Two study groups were compared based upon self-reporting data: smokers (n = 32; continual cigarette smoking 3 months before and 9 months during pregnancy) and nonsmokers (n = 54; including passive smokers whose parameters did not differ from unexposed nonsmokers). In smokers compared to nonsmokers maternal hair nicotine concentrations increased approximately sevenfold, while Cd levels rose fourfold in maternal blood and up to twofold in placenta. Significant positive correlations were noted between maternal hair nicotine and placental Cd, maternal hair nicotine and maternal blood Cd, and placental Cd and maternal blood Cd. Levels of cord blood Cd were low in both study groups (<0.1 ng/ml). Data indicate that Cd in placenta may serve as a noninvasive bioindicator in addition to commonly used noninvasive hair nicotine in maternal TS assessment, especially in cases where unavailable or inappropriate (short or chemically treated) hair samples occur. PMID:27210017

  9. Placental cadmium as an additional noninvasive bioindicator of active maternal tobacco smoking.

    PubMed

    Piasek, Martina; Jurasović, Jasna; Sekovanić, Ankica; Brajenović, Nataša; Brčić Karačonji, Irena; Mikolić, Anja; Grgec, Antonija Sulimanec; Stasenko, Sandra

    2016-01-01

    Tobacco smoke (TS) is a mixture of chemicals that is known to exert carcinogenic and endocrine-disrupting effects, as well as adverse effects on various systems. In TS nicotine is the major alkaloid and cadmium (Cd) the most abundant metal ion. The aim of this investigation was to assess exposure to Cd attributed to TS in healthy postpartum subjects (mean age 28 years) after term vaginal delivery in a clinical hospital by determining metal levels in maternal blood, placenta, and cord blood in relation to nicotine in maternal hair (12-cm-long samples). Two study groups were compared based upon self-reporting data: smokers (n = 32; continual cigarette smoking 3 months before and 9 months during pregnancy) and nonsmokers (n = 54; including passive smokers whose parameters did not differ from unexposed nonsmokers). In smokers compared to nonsmokers maternal hair nicotine concentrations increased approximately sevenfold, while Cd levels rose fourfold in maternal blood and up to twofold in placenta. Significant positive correlations were noted between maternal hair nicotine and placental Cd, maternal hair nicotine and maternal blood Cd, and placental Cd and maternal blood Cd. Levels of cord blood Cd were low in both study groups (<0.1 ng/ml). Data indicate that Cd in placenta may serve as a noninvasive bioindicator in addition to commonly used noninvasive hair nicotine in maternal TS assessment, especially in cases where unavailable or inappropriate (short or chemically treated) hair samples occur.

  10. A Dyadic Approach to Understanding the Relationship of Maternal Knowledge of Youths' Activities to Youths' Problem Behavior among Rural Adolescents

    ERIC Educational Resources Information Center

    Lippold, Melissa A.; Greenberg, Mark T.; Feinberg, Mark E.

    2011-01-01

    Most studies that explore parental knowledge of youths' activities utilize parents' and youths' reports separately. Using a sample of 938 rural early adolescents (53% female; 84% White), we explore congruence between mothers' and youths' perceptions of maternal knowledge and its association with youth problem behaviors (delinquency, substance use,…

  11. Maternal High-Fat Feeding Increases Placental Lipoprotein Lipase Activity by Reducing SIRT1 Expression in Mice

    PubMed Central

    Qiao, Liping; Guo, Zhuyu; Bosco, Chris; Guidotti, Stefano; Wang, Yunfeng; Wang, Mingyong; Parast, Mana; Schaack, Jerome; Hay, William W.; Moore, Thomas R.

    2015-01-01

    This study investigated how maternal overnutrition and obesity regulate expression and activation of proteins that facilitate lipid transport in the placenta. To create a maternal overnutrition and obesity model, primiparous C57BL/6 mice were fed a high-fat (HF) diet throughout gestation. Fetuses from HF-fed dams had significantly increased serum levels of free fatty acid and body fat. Despite no significant difference in placental weight, lipoprotein lipase (LPL) protein levels and activity were remarkably elevated in placentas from HF-fed dams. Increased triglyceride content and mRNA levels of CD36, VLDLr, FABP3, FABPpm, and GPAT2 and -3 were also found in placentas from HF-fed dams. Although both peroxisome proliferator–activated receptor-γ (PPARγ) and CCAAT/enhancer binding protein-α protein levels were significantly increased in placentas of the HF group, only PPARγ exhibited a stimulative effect on LPL expression in cultured JEG-3 human trophoblasts. Maternal HF feeding remarkably decreased SIRT1 expression in placentas. Through use of an SIRT1 activator and inhibitor and cultured trophoblasts, an inhibitory effect of SIRT1 on LPL expression was demonstrated. We also found that SIRT1 suppresses PPARγ expression in trophoblasts. Most importantly, inhibition of PPARγ abolished the SIRT1-mediated regulatory effect on LPL expression. Together, these results indicate that maternal overnutrition induces LPL expression in trophoblasts by reducing the inhibitory effect of SIRT1 on PPARγ. PMID:25948680

  12. Limbic brain activation for maternal acoustic perception and responding is different in mothers and virgin female mice.

    PubMed

    Geissler, Diana B; Sabine Schmidt, H; Ehret, Günter

    2013-01-01

    Mothers are primed to become maternal through hormonal changes during pregnancy and delivery of young, virgin females need experience with young for performing maternally. The activation of brain areas controlling maternal behavior can be studied by stimulus-induced expression of the immediate-early gene Fos and immunocytochemical labeling of the FOS protein in activated cells. With this technique we identified areas of the mouse limbic system stimulated by acoustically adequate or inadequate models of pup ultrasounds that, if perceived as adequate, direct the search for lost pups (phonotaxis). Behavioral observations and neural activation data suggest that adequate (50 kHz long tones) and inadequate ultrasound models (50 kHz short or 20 kHz long tones) are differently processed in limbic areas of mothers and virgin females with 1 or 5 days of pup-caring experience depending on the news value and the recognition of the stimuli: High numbers of FOS-positive cells in the medial preoptic area, lateral septum, and bed nucleus of the stria terminalis (mothers and virgins) relate to the salience (news value) of the perceived sounds; contextual stress may be reflected by high activation in parts of the amygdala and the ventromedial hypothalamus (virgins); high activation in the piriform cortex suggests associative learning of adequate sounds and in the entorhinal cortex remembering associations of adequate sounds with pups (virgins). Thus brain areas were differently activated in animals with maternal emotions, however different responses to pup cues depending on how they got primed to behave maternally and on how they evaluated the stimulation context.

  13. Regulatory T cells and the immune pathogenesis of prenatal infection.

    PubMed

    Rowe, Jared H; Ertelt, James M; Xin, Lijun; Way, Sing Sing

    2013-12-01

    Pregnancy in placental mammals offers exceptional comprehensive benefits of in utero protection, nutrition, and metabolic waste elimination for the developing fetus. However, these benefits also require durable strategies to mitigate maternal rejection of fetal tissues expressing foreign paternal antigens. Since the initial postulate of expanded maternal immune tolerance by Sir Peter Medawar 60 years ago, an amazingly elaborate assortment of molecular and cellular modifications acting both locally at the maternal-placental interface and systemically have been shown to silence potentially detrimental maternal immune responses. In turn, simultaneously maintaining host defense against the infinite array of potential pathogens during pregnancy is equally important. Fortunately, resistance against most infections is preserved seamlessly throughout gestation. On the other hand, recent studies on pathogens with unique predisposition for prenatal infections have uncovered distinctive holes in host defense associated with the reproductive process. Using these infections to probe the response during pregnancy, the immune suppressive regulatory subset of maternal CD4 T cells has been increasingly shown to dictate the inter-workings between prenatal infection susceptibility and pathogenesis of ensuing pregnancy complications. Herein, the recent literature suggesting a necessity for maternal regulatory T cells (Tregs) in pregnancy-induced immunological shifts that sustain fetal tolerance is reviewed. Additional discussion is focused on how expansion of maternal Treg suppression may become exploited by pathogens that cause prenatal infections and the perilous potential of infection-induced immune activation that may mitigate fetal tolerance and inadvertently inject hostility into the protective in utero environment.

  14. Effect of balanced low pressure drying of curcuma longa leaf on skin immune activation activities.

    PubMed

    Choi, Wooseok; Lim, Hye Won; Lee, Hyeon Yong

    2014-01-01

    The effect of balanced low pressure drying pretreatment associated with ultrasonication extraction (BU) on the enhancement of skin immune modulatory activities of Curcuma longa leaf was studied by comparing with conventional hot air drying (HE), freeze drying (FE) and balanced low pressure drying (BE) pretreatment processes. In considering skin immune activation activities such as the inhibition of hyaluronidase activity, the BU extract showed ca. 10% higher than those of HE, and even higher than that of the FE extract. Nitric oxide production from macrophage of the BU extract in adding 1.0 mg/mL was increased up to 16.5 μM. When measuring inhibition of IL-6 and TNF-a production from the human T lymphocytes (T cell), the BU extract also showed 53% and 78% of inhibition effect, respectively. It is found that the BU extract could effectively suppress the expression levels of skin inflammation related genes such as Cox-2 and iNOS, down to 80% and 85% compared to the control, respectively. Balanced low pressure drying process was especially active on dehydration of the leaves with minimizing the destruction and making easier elution of the bioactive substances, which resulted in higher extraction yield and better biological activities.

  15. Role of Active and Inactive Cytotoxic Immune Response in Human Immunodeficiency Virus Dynamics

    PubMed Central

    Toro Zapata, Hernan Dario; Caicedo Casso, Angelica Graciela; Bichara, Derdei; Lee, Sunmi

    2014-01-01

    Objectives Mathematical models can be helpful to understand the complex dynamics of human immunodeficiency virus infection within a host. Most of work has studied the interactions of host responses and virus in the presence of active cytotoxic immune cells, which decay to zero when there is no virus. However, recent research highlights that cytotoxic immune cells can be inactive but never be depleted. Methods We propose a mathematical model to investigate the human immunodeficiency virus dynamics in the presence of both active and inactive cytotoxic immune cells within a host. We explore the impact of the immune responses on the dynamics of human immunodeficiency virus infection under different disease stages. Results Standard mathematical and numerical analyses are presented for this new model. Specifically, the basic reproduction number is computed and local and global stability analyses are discussed. Conclusion Our results can give helpful insights when designing more effective drug schedules in the presence of active and inactive immune responses. PMID:24955306

  16. Vibriocidal activity, immune globulin producing cells and immune globulin levels in Theropithecus gelada after administration of a Vibrio cholerae antigen

    PubMed Central

    Felsenfeld, Oscar; Greer, William E.

    1968-01-01

    Geladas were fed or injected with an antigen that contained Burrows' type 2 cholera toxin. Rising agglutinin and vibriocidal titres were observed in the serum, peripheral and mesenteric lymph nodes, spleen and lymphatic tissue of the upper intestine. Oral administration stimulated a more intensive vibriocidal activity in the mesenteric lymphatic nodes and intestinal lymphatic tissue, and within a shorter time than parenteral injection of the same antigen. Immune globulin synthesis paralleled largely the number of immunologically active cells. The agglutinin titres reflected the level of immune globulins and the numbers of globulin producing cells, whereas vibriocidal titres appeared independent of both. In terms of antibody site serum IgG was weight for weight more vibriocidal than serum IgM. PMID:4170509

  17. Long-term activation of the innate immune system in atherosclerosis.

    PubMed

    Christ, Anette; Bekkering, Siroon; Latz, Eicke; Riksen, Niels P

    2016-08-01

    Efforts to reverse the pathologic consequences of vulnerable plaques are often stymied by the complex treatment resistant pro-inflammatory environment within the plaque. This suggests that pro-atherogenic stimuli, such as LDL cholesterol and high fat diets may impart longer lived signals on (innate) immune cells that persist even after reversing the pro-atherogenic stimuli. Recently, a series of studies challenged the traditional immunological paradigm that innate immune cells cannot display memory characteristics. Epigenetic reprogramming in these myeloid cell subsets, after exposure to certain stimuli, has been shown to alter the expression of genes upon re-exposure. This phenomenon has been termed trained innate immunity or innate immune memory. The changed responses of 'trained' innate immune cells can confer nonspecific protection against secondary infections, suggesting that innate immune memory has likely evolved as an ancient mechanism to protect against pathogens. However, dysregulated processes of immunological imprinting mediated by trained innate immunity may also be detrimental under certain conditions as the resulting exaggerated immune responses could contribute to autoimmune and inflammatory diseases, such as atherosclerosis. Pro-atherogenic stimuli most likely cause epigenetic modifications that persist for prolonged time periods even after the initial stimulus has been removed. In this review we discuss the concept of trained innate immunity in the context of a hyperlipidemic environment and atherosclerosis. According to this idea the epigenome of myeloid (progenitor) cells is presumably modified for prolonged periods of time, which, in turn, could evoke a condition of continuous immune cell over-activation.

  18. Nutritionally Mediated Programming of the Developing Immune System12

    PubMed Central

    Palmer, Amanda C.

    2011-01-01

    A growing body of evidence highlights the importance of a mother’s nutrition from preconception through lactation in programming the emerging organ systems and homeostatic pathways of her offspring. The developing immune system may be particularly vulnerable. Indeed, examples of nutrition-mediated immune programming can be found in the literature on intra-uterine growth retardation, maternal micronutrient deficiencies, and infant feeding. Current models of immune ontogeny depict a “layered” expansion of increasingly complex defenses, which may be permanently altered by maternal malnutrition. One programming mechanism involves activation of the maternal hypothalamic-pituitary-adrenal axis in response to nutritional stress. Fetal or neonatal exposure to elevated stress hormones is linked in animal studies to permanent changes in neuroendocrine-immune interactions, with diverse manifestations such as an attenuated inflammatory response or reduced resistance to tumor colonization. Maternal malnutrition may also have a direct influence, as evidenced by nutrient-driven epigenetic changes to developing T regulatory cells and subsequent risk of allergy or asthma. A 3rd programming pathway involves placental or breast milk transfer of maternal immune factors with immunomodulatory functions (e.g. cytokines). Maternal malnutrition can directly affect transfer mechanisms or influence the quality or quantity of transferred factors. The public health implications of nutrition-mediated immune programming are of particular importance in the developing world, where prevalent maternal undernutrition is coupled with persistent infectious challenges. However, early alterations to the immune system, resulting from either nutritional deficiencies or excesses, have broad relevance for immune-mediated diseases, such as asthma, and chronic inflammatory conditions like cardiovascular disease. PMID:22332080

  19. Office of Maternal and Child Health Active Projects FY 1989. An Annotated Listing.

    ERIC Educational Resources Information Center

    National Center for Education in Maternal and Child Health, Washington, DC.

    An annotated listing is presented of projects offering maternal and child health care services. These projects, referred to as special projects of regional and national significance (SPRANS), are supported by the Office of Maternal and Child Health of the Department of Health and Human Services. The first section provides information on services…

  20. Role of lipids in the metabolism and activation of immune cells.

    PubMed

    Hubler, Merla J; Kennedy, Arion J

    2016-08-01

    Immune cell plasticity has extensive implications in the pathogenesis and resolution of metabolic disorders, cancers, autoimmune diseases and chronic inflammatory disorders. Over the past decade, nutritional status has been discovered to influence the immune response. In metabolic disorders such as obesity, immune cells interact with various classes of lipids, which are capable of controlling the plasticity of macrophages and T lymphocytes. The purpose of this review is to discuss lipids and their impact on innate and adaptive immune responses, focusing on two areas: (1) the impact of altering lipid metabolism on immune cell activation, differentiation and function and (2) the mechanism by which lipids such as cholesterol and fatty acids regulate immune cell plasticity.

  1. Maternal Eating and Physical Activity Strategies and their Relation with Children's Nutritional Status1

    PubMed Central

    Flores-Peña, Yolanda; Ortiz-Félix, Rosario Edith; Cárdenas-Villarreal, Velia Margarita; Ávila-Alpirez, Hermelinda; Alba-Alba, Corina Mariela; Hernández-Carranco, Roandy Gaspar

    2014-01-01

    Objectives to describe the maternal eating and physical activity strategies (monitoring, discipline, control, limits and reinforcement) [MEES]; to determine the relation between MEES and the child's nutritional status [body mass index (BMI) and body fat percentage (BFP)]; to verify whether the MEES differ according to the child's nutritional status. Method participants were 558 mothers and children (3 to 11 years of age) who studied at public schools. The Parental Strategies for Eating and Activity Scale (PEAS) was applied and the child's weight, height and BFP were measured. For analysis purposes, descriptive statistics were obtained, using multiple linear regression and the Kruskal-Wallis test. Results the highest mean score was found for reinforcement (62.72) and the lowest for control (50.07). Discipline, control and limits explained 12% of the BMI, while discipline and control explained 6% of the BFP. Greater control is found for obese children (χ2=38.36, p=0.001) and greater reinforcement for underweight children (χ2=7.19, p<0.05). Conclusions the mothers exert greater control (pressure to eat) over obese children and greater recognition (congratulating due to healthy eating) in underweight children. Modifications in parental strategies are recommended with a view to strengthening healthy eating and physical activity habits. PMID:26107837

  2. Immune activity elevates energy expenditure of house sparrows: a link between direct and indirect costs?

    PubMed Central

    Martin, Lynn B; Scheuerlein, Alex; Wikelski, Martin

    2003-01-01

    The activation of an immune response is beneficial for organisms but may also have costs that affect fitness. Documented immune costs include those associated with acquisition of special nutrients, as well as immunopathology or autoimmunity. Here, we test whether an experimental induction of the immune system with a non-pathological stimulant can elevate energy turnover in passerine birds. We injected phytohaemagglutinin (PHA), a commonly used mitogen that activates the cell-mediated immune response, into the wing web of house sparrows, Passer domesticus. We then examined energetic costs resulting from this immune activity and related those costs to other physiological activities. We found that PHA injection significantly elevated resting metabolic rate (RMR) of challenged sparrows relative to saline controls. We calculated the total cost of this immune activity to be ca. 4.20 kJ per day (29% RMR), which is equivalent to the cost of production of half of an egg (8.23 kJ egg(-1)) in this species. We suggest that immune activity in wild passerines increases energy expenditure, which in turn may influence important life-history characteristics such as clutch size, timing of breeding or the scheduling of moult. PMID:12590753

  3. Gender differences in the immune system activities of sea urchin Paracentrotus lividus.

    PubMed

    Arizza, Vincenzo; Vazzana, Mirella; Schillaci, Domenico; Russo, Debora; Giaramita, Francesca Tiziana; Parrinello, Nicolò

    2013-03-01

    In the immune system of vertebrates, gender-specific differences in individual immune competence are well known. In general, females possess more powerful immune response than males. In invertebrates, the situation is much less clear. For this purpose we have chosen to study the immune response of the two sexes of the echinoderm Paracentrotus lividus in pre- and post-spawning phases. The coelomic fluid from the echinoderms contains several coelomocyte types and molecules involved in innate immune defenses. In this article we report that the degree of immune responses in the P. lividus differs according to sex in both pre- and post-spawning phases. We found in all tests that females were more active than males. The results indicate that females possess a significant higher number of immunocytes consisting of phagocytes and uncolored spherulocytes. Since the immunological activity is mainly based on immunocytes, it was not surprising that females possessed the highest values of cytotoxicity and hemolysis activity and showed a greater ability to uptake neutral red and phagocyte yeasts cells, while the average number of ingested particles per active phagocyte was not significantly different. Furthermore, agglutinating activity was more evident in the coelomocyte lysate and coelomic fluid of females than in those of males. Finally we found that the acidic extract of female gonads possessed greater antimicrobial activity than that of male gonads. These results make it very likely that gender differences in the immune response are not restricted to vertebrates; rather, they are a general evolutionary phenomenon.

  4. Immune activity elevates energy expenditure of house sparrows: a link between direct and indirect costs?

    PubMed

    Martin, Lynn B; Scheuerlein, Alex; Wikelski, Martin

    2003-01-22

    The activation of an immune response is beneficial for organisms but may also have costs that affect fitness. Documented immune costs include those associated with acquisition of special nutrients, as well as immunopathology or autoimmunity. Here, we test whether an experimental induction of the immune system with a non-pathological stimulant can elevate energy turnover in passerine birds. We injected phytohaemagglutinin (PHA), a commonly used mitogen that activates the cell-mediated immune response, into the wing web of house sparrows, Passer domesticus. We then examined energetic costs resulting from this immune activity and related those costs to other physiological activities. We found that PHA injection significantly elevated resting metabolic rate (RMR) of challenged sparrows relative to saline controls. We calculated the total cost of this immune activity to be ca. 4.20 kJ per day (29% RMR), which is equivalent to the cost of production of half of an egg (8.23 kJ egg(-1)) in this species. We suggest that immune activity in wild passerines increases energy expenditure, which in turn may influence important life-history characteristics such as clutch size, timing of breeding or the scheduling of moult.

  5. Contribution of Immune Activation to the Pathogenesis and Transmission of Human Immunodeficiency Virus Type 1 Infection

    PubMed Central

    Lawn, Stephen D.; Butera, Salvatore T.; Folks, Thomas M.

    2001-01-01

    The life cycle of human immunodeficiency virus type 1 (HIV-1) is intricately related to the activation state of the host cells supporting viral replication. Although cellular activation is essential to mount an effective host immune response to invading pathogens, paradoxically the marked systemic immune activation that accompanies HIV-1 infection in vivo may play an important role in sustaining phenomenal rates of HIV-1 replication in infected persons. Moreover, by inducing CD4+ cell loss by apoptosis, immune activation may further be central to the increased rate of CD4+ cell turnover and eventual development of CD4+ lymphocytopenia. In addition to HIV-1-induced immune activation, exogenous immune stimuli such as opportunistic infections may further impact the rate of HIV-1 replication systemically or at localized anatomical sites. Such stimuli may also lead to genotypic and phenotypic changes in the virus pool. Together, these various immunological effects on the biology of HIV-1 may potentially enhance disease progression in HIV-infected persons and may ultimately outweigh the beneficial aspects of antiviral immune responses. This may be particularly important for those living in developing countries, where there is little or no access to antiretroviral drugs and where frequent exposure to pathogenic organisms sustains a chronically heightened state of immune activation. Moreover, immune activation associated with sexually transmitted diseases, chorioamnionitis, and mastitis may have important local effects on HIV-1 replication that may increase the risk of sexual or mother-to-child transmission of HIV-1. The aim of this paper is to provide a broad review of the interrelationship between immune activation and the immunopathogenesis, transmission, progression, and treatment of HIV-1 infection in vivo. PMID:11585784

  6. Mild maternal iron deficiency anemia induces DPOAE suppression and cochlear hair cell apoptosis by caspase activation in young guinea pigs.

    PubMed

    Yu, Fei; Hao, Shuai; Zhao, Yue; Ren, Yahao; Yang, Jun; Sun, Xiance; Chen, Jie

    2014-01-01

    Iron deficiency (ID) anemia (IDA) alters auditory neural normal development in the mammalian cochlea. Previous results suggest that mild maternal IDA during pregnancy and lactation altered the hearing and nervous system development of the young offspring, but the mechanisms underlying the association are incompletely understood. The objective of this study was to evaluate the role of apoptosis in the development of sensory hair cells following mild maternal IDA during pregnancy and lactation. We established a maternal anemia model in female guinea pigs by using a mild iron deficient diet. The offspring were weaned on postnatal day (PND) 9 and then was given the iron sufficient diet. Maternal blood samples were collected on gestational day (GD) 21, GD 42, GD 63 and PND 9, serum level of iron (SI) or hemoglobin (Hb) was measured. Blood samples of pups were collected on PND 9 for SI measurement. On PND 24, pups were examined the distortion product otoacoustic emission (DPOAE) task, and then the cochleae were harvested for assessment of apoptosis by immunohistochemistry of cysteine-aspartic acid proteases 3/9 (caspase-3/9) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, and by double immunofluorescence for the colocalization of TUNEL and caspase-3. Blood samples of pups were collected on PND 24 for SI and Hb measurements. Here we show that mild maternal IDA during pregnancy and lactation resulted in hearing impairment, decreased hair cell number, caspase-3/9 activation and increased apoptotic cell number of young guinea pigs. These results indicate a key role for apoptosis in inhibition of hair cell development, caused by mild maternal IDA during pregnancy and lactation. PMID:24378594

  7. Associations of maternal organophosphate pesticide exposure and PON1 activity with birth outcomes in SAWASDEE birth cohort, Thailand.

    PubMed

    Naksen, Warangkana; Prapamontol, Tippawan; Mangklabruks, Ampica; Chantara, Somporn; Thavornyutikarn, Prasak; Srinual, Niphan; Panuwet, Parinya; Ryan, P Barry; Riederer, Anne M; Barr, Dana Boyd

    2015-10-01

    Prenatal organophosphate (OP) pesticide exposure has been reported to be associated with adverse birth outcomes and neurodevelopment. However, the mechanisms of toxicity of OP pesticides on human fetal development have not yet been elucidated. Our pilot study birth cohort, the Study of Asian Women and Offspring's Development and Environmental Exposures (SAWASDEE cohort) aimed to evaluate environmental chemical exposures and their relation to birth outcomes and infant neurodevelopment in 52 pregnant farmworkers in Fang district, Chiang Mai province, Thailand. A large array of data was collected multiple times during pregnancy including approximately monthly urine samples for evaluation of pesticide exposure, three blood samples for pesticide-related enzyme measurements and questionnaire data. This study investigated the changes in maternal acetylcholinesterase (AChE) and paraoxonase 1 (PON1) activities and their relation to urinary diakylphosphates (DAPs), class-related metabolites of OP pesticides, during pregnancy. Maternal AChE, butyrylcholinesterase (BChE) and PON1 activities were measured three times during pregnancy and urinary DAP concentrations were measured, on average, 8 times from enrollment during pregnancy until delivery. Among the individuals in the group with low maternal PON1 activity (n=23), newborn head circumference was negatively correlated with log10 maternal ∑DEAP and ∑DAP at enrollment (gestational age=12±3 weeks; β=-1.0 cm, p=0.03 and β=-1.8 cm, p<0.01, respectively) and at 32 weeks pregnancy (β=-1.1cm, p=0.04 and β=-2.6 cm, p=0.01, respectively). Furthermore, among these mothers, newborn birthweight was also negatively associated with log10 maternal ∑DEAP and ∑DAP at enrollment (β=-219.7 g, p=0.05 and β=-371.3g, p=0.02, respectively). Associations between maternal DAP levels and newborn outcomes were not observed in the group of participants with high maternal PON1 activity. Our results support previous findings from US birth

  8. CIP2A Promotes T-Cell Activation and Immune Response to Listeria monocytogenes Infection.

    PubMed

    Côme, Christophe; Cvrljevic, Anna; Khan, Mohd Moin; Treise, Irina; Adler, Thure; Aguilar-Pimentel, Juan Antonio; Au-Yeung, Byron; Sittig, Eleonora; Laajala, Teemu Daniel; Chen, Yiling; Oeder, Sebastian; Calzada-Wack, Julia; Horsch, Marion; Aittokallio, Tero; Busch, Dirk H; Ollert, Markus W; Neff, Frauke; Beckers, Johannes; Gailus-Durner, Valerie; Fuchs, Helmut; Hrabě de Angelis, Martin; Chen, Zhi; Lahesmaa, Riitta; Westermarck, Jukka

    2016-01-01

    The oncoprotein Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A) is overexpressed in most malignancies and is an obvious candidate target protein for future cancer therapies. However, the physiological importance of CIP2A-mediated PP2A inhibition is largely unknown. As PP2A regulates immune responses, we investigated the role of CIP2A in normal immune system development and during immune response in vivo. We show that CIP2A-deficient mice (CIP2AHOZ) present a normal immune system development and function in unchallenged conditions. However when challenged with Listeria monocytogenes, CIP2AHOZ mice display an impaired adaptive immune response that is combined with decreased frequency of both CD4+ T-cells and CD8+ effector T-cells. Importantly, the cell autonomous effect of CIP2A deficiency for T-cell activation was confirmed. Induction of CIP2A expression during T-cell activation was dependent on Zap70 activity. Thus, we reveal CIP2A as a hitherto unrecognized mediator of T-cell activation during adaptive immune response. These results also reveal CIP2AHOZ as a possible novel mouse model for studying the role of PP2A activity in immune regulation. On the other hand, the results also indicate that CIP2A targeting cancer therapies would not cause serious immunological side-effects.

  9. Virus-associated activation of innate immunity induces rapid disruption of Peyer's patches in mice.

    PubMed

    Heidegger, Simon; Anz, David; Stephan, Nicolas; Bohn, Bernadette; Herbst, Tina; Fendler, Wolfgang Peter; Suhartha, Nina; Sandholzer, Nadja; Kobold, Sebastian; Hotz, Christian; Eisenächer, Katharina; Radtke-Schuller, Susanne; Endres, Stefan; Bourquin, Carole

    2013-10-10

    Early in the course of infection, detection of pathogen-associated molecular patterns by innate immune receptors can shape the subsequent adaptive immune response. Here we investigate the influence of virus-associated innate immune activation on lymphocyte distribution in secondary lymphoid organs. We show for the first time that virus infection of mice induces rapid disruption of the Peyer's patches but not of other secondary lymphoid organs. The observed effect was not dependent on an active infectious process, but due to innate immune activation and could be mimicked by virus-associated molecular patterns such as the synthetic double-stranded RNA poly(I:C). Profound histomorphologic changes in Peyer's patches were associated with depletion of organ cellularity, most prominent among the B-cell subset. We demonstrate that the disruption is entirely dependent on type I interferon (IFN). At the cellular level, we show that virus-associated immune activation by IFN-α blocks B-cell trafficking to the Peyer's patches by downregulating expression of the homing molecule α4β7-integrin. In summary, our data identify a mechanism that results in type I IFN-dependent rapid but reversible disruption of intestinal lymphoid organs during systemic viral immune activation. We propose that such rerouted lymphocyte trafficking may impact the development of B-cell immunity to systemic viral pathogens. PMID:23823318

  10. CIP2A Promotes T-Cell Activation and Immune Response to Listeria monocytogenes Infection

    PubMed Central

    Cvrljevic, Anna; Khan, Mohd Moin; Treise, Irina; Adler, Thure; Aguilar-Pimentel, Juan Antonio; Au-Yeung, Byron; Sittig, Eleonora; Laajala, Teemu Daniel; Chen, Yiling; Oeder, Sebastian; Calzada-Wack, Julia; Horsch, Marion; Aittokallio, Tero; Busch, Dirk H.; Ollert, Markus W.; Neff, Frauke; Beckers, Johannes; Gailus-Durner, Valerie; Fuchs, Helmut; de Angelis, Martin Hrabě; Chen, Zhi; Lahesmaa, Riitta; Westermarck, Jukka

    2016-01-01

    The oncoprotein Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A) is overexpressed in most malignancies and is an obvious candidate target protein for future cancer therapies. However, the physiological importance of CIP2A-mediated PP2A inhibition is largely unknown. As PP2A regulates immune responses, we investigated the role of CIP2A in normal immune system development and during immune response in vivo. We show that CIP2A-deficient mice (CIP2AHOZ) present a normal immune system development and function in unchallenged conditions. However when challenged with Listeria monocytogenes, CIP2AHOZ mice display an impaired adaptive immune response that is combined with decreased frequency of both CD4+ T-cells and CD8+ effector T-cells. Importantly, the cell autonomous effect of CIP2A deficiency for T-cell activation was confirmed. Induction of CIP2A expression during T-cell activation was dependent on Zap70 activity. Thus, we reveal CIP2A as a hitherto unrecognized mediator of T-cell activation during adaptive immune response. These results also reveal CIP2AHOZ as a possible novel mouse model for studying the role of PP2A activity in immune regulation. On the other hand, the results also indicate that CIP2A targeting cancer therapies would not cause serious immunological side-effects. PMID:27100879

  11. Virus-associated activation of innate immunity induces rapid disruption of Peyer's patches in mice.

    PubMed

    Heidegger, Simon; Anz, David; Stephan, Nicolas; Bohn, Bernadette; Herbst, Tina; Fendler, Wolfgang Peter; Suhartha, Nina; Sandholzer, Nadja; Kobold, Sebastian; Hotz, Christian; Eisenächer, Katharina; Radtke-Schuller, Susanne; Endres, Stefan; Bourquin, Carole

    2013-10-10

    Early in the course of infection, detection of pathogen-associated molecular patterns by innate immune receptors can shape the subsequent adaptive immune response. Here we investigate the influence of virus-associated innate immune activation on lymphocyte distribution in secondary lymphoid organs. We show for the first time that virus infection of mice induces rapid disruption of the Peyer's patches but not of other secondary lymphoid organs. The observed effect was not dependent on an active infectious process, but due to innate immune activation and could be mimicked by virus-associated molecular patterns such as the synthetic double-stranded RNA poly(I:C). Profound histomorphologic changes in Peyer's patches were associated with depletion of organ cellularity, most prominent among the B-cell subset. We demonstrate that the disruption is entirely dependent on type I interferon (IFN). At the cellular level, we show that virus-associated immune activation by IFN-α blocks B-cell trafficking to the Peyer's patches by downregulating expression of the homing molecule α4β7-integrin. In summary, our data identify a mechanism that results in type I IFN-dependent rapid but reversible disruption of intestinal lymphoid organs during systemic viral immune activation. We propose that such rerouted lymphocyte trafficking may impact the development of B-cell immunity to systemic viral pathogens.

  12. Innate immune system activation by viral RNA: How to predict it?

    PubMed

    Kondili, M; Roux, M; Vabret, N; Bailly-Bechet, M

    2016-01-15

    The immune system is able to identify foreign pathogens via different pathways. In the case of viral infection, recognition of the viral RNA is a crucial step, and many efforts have been made to understand which features of viral RNA are detected by the immune system. The biased viral RNA composition, measured as host-virus nucleotidic divergence, or CpG enrichment, has been proposed as salient signal. Peculiar structural features of these RNA could also be related to the immune system activation. Here, we gather multiple datasets and proceed to a meta-analysis to uncover the best predictors of immune system activation by viral RNA. "A" nucleotide content and Minimum Folding Energy are good predictors, and are more easily generalized than more complex indicators suggested previously. As RNA composition and structure are highly correlated, we suggest further experiments on synthetic sequences to identify the viral RNA sensing mechanisms by immune system receptors.

  13. Innate immune system activation by viral RNA: How to predict it?

    PubMed

    Kondili, M; Roux, M; Vabret, N; Bailly-Bechet, M

    2016-01-15

    The immune system is able to identify foreign pathogens via different pathways. In the case of viral infection, recognition of the viral RNA is a crucial step, and many efforts have been made to understand which features of viral RNA are detected by the immune system. The biased viral RNA composition, measured as host-virus nucleotidic divergence, or CpG enrichment, has been proposed as salient signal. Peculiar structural features of these RNA could also be related to the immune system activation. Here, we gather multiple datasets and proceed to a meta-analysis to uncover the best predictors of immune system activation by viral RNA. "A" nucleotide content and Minimum Folding Energy are good predictors, and are more easily generalized than more complex indicators suggested previously. As RNA composition and structure are highly correlated, we suggest further experiments on synthetic sequences to identify the viral RNA sensing mechanisms by immune system receptors. PMID:26650692

  14. Effect of maternal deprivation on N-acetyltransferase activity rhythm in blinded rat pups.

    PubMed

    Katoh, Y; Takeuchi, Y; Yamazaki, K; Takahashi, K

    1998-02-15

    It has been reported that the rhythms of infant rats synchronize with the mother's rhythm until the light-dark cycle comes and has strong effects on their endogenous clocks. We found that periodic maternal deprivation (PMD) was able to cause a phase shift of serotonin N-acetyltransferase (NAT) in neonatal blinded rat pups. PMD in which contact with the mother was allowed for only 4 h caused a phase shift of NAT rhythm, irrespective of the timing of contact with the mother in a day. Acute single mother deprivation caused an excess of NAT activity for more hours than usual and contact with the mother prevented such an excessive response. Mother deprivation may act as a cold stress, since artificial warming of pups gave the same results as contact with the mother. When the pups were artificially warmed by a heater during a 1-week deprivation period, a flat 24-h pattern of NAT was observed. The mechanism causing a phase shift of NAT activity rhythm of rat pups may be complicated. PMID:9523895

  15. Responses of ram lambs to active immunization against testosterone and luteinizing hormone-releasing hormone.

    PubMed

    Schanbacher, B D

    1982-03-01

    Active immunization of young ram lambs against testosterone and luteinizing hormone-releasing hormone (LHRH) was shown to block the growth attributes characteristic of intact ram lambs. Testosterone and LHRH-immunized lambs grew at a slower rate and converted feed to live weight gain less efficiently than albumin-immunized controls. Lambs immunized against testosterone and LHRH had high antibody titers for their respective antigens. Moreover, testosterone-immunized lambs had high serum concentrations of luteinizing hormone (LH) and testosterone, whereas LHRH-immunized lambs had low to nondetectable serum concentrations of these hormones. Release of LH and testosterone following the intravenous administration of LHRH (250 ng) was absent in LHRH-immunized lambs, but quantitatively similar for intact and albumin-immunized control lambs. Testosterone-immunized lambs responded as did conventional castrates with a large LH release, but testosterone concentrations were unchanged. These findings are discussed relative to the integrity of the hypothalamic-pituitary-testicular endocrine axis and the importance of gonadotropin support for normal testicular development. These data show that LHRH immunoneutralization effectively retards testicular development and produces a castration effect in young ram lambs.

  16. From Wasting to Obesity: The Contribution of Nutritional Status to Immune Activation in HIV Infection.

    PubMed

    Koethe, John R; Heimburger, Douglas C; PrayGod, George; Filteau, Suzanne

    2016-10-01

    The impact of human immunodeficiency virus (HIV) infection on innate and adaptive immune activation occurs in the context of host factors, which serve to augment or dampen the physiologic response to the virus. Independent of HIV infection, nutritional status, particularly body composition, affects innate immune activation through a variety of conditions, including reduced mucosal barrier defenses and microbiome dysbiosis in malnutrition and the proinflammatory contribution of adipocytes and stromal vascular cells in obesity. Similarly, T-cell activation, proliferation, and cytokine expression are reduced in the setting of malnutrition and increased in obesity, potentially due to adipokine regulatory mechanisms restraining energy-avid adaptive immunity in times of starvation and exerting a paradoxical effect in overnutrition. The response to HIV infection is situated within these complex interactions between host nutritional health and immunologic function, which contribute to the varied phenotypes of immune activation among HIV-infected patients across a spectrum from malnutrition to obesity.

  17. From Wasting to Obesity: The Contribution of Nutritional Status to Immune Activation in HIV Infection.

    PubMed

    Koethe, John R; Heimburger, Douglas C; PrayGod, George; Filteau, Suzanne

    2016-10-01

    The impact of human immunodeficiency virus (HIV) infection on innate and adaptive immune activation occurs in the context of host factors, which serve to augment or dampen the physiologic response to the virus. Independent of HIV infection, nutritional status, particularly body composition, affects innate immune activation through a variety of conditions, including reduced mucosal barrier defenses and microbiome dysbiosis in malnutrition and the proinflammatory contribution of adipocytes and stromal vascular cells in obesity. Similarly, T-cell activation, proliferation, and cytokine expression are reduced in the setting of malnutrition and increased in obesity, potentially due to adipokine regulatory mechanisms restraining energy-avid adaptive immunity in times of starvation and exerting a paradoxical effect in overnutrition. The response to HIV infection is situated within these complex interactions between host nutritional health and immunologic function, which contribute to the varied phenotypes of immune activation among HIV-infected patients across a spectrum from malnutrition to obesity. PMID:27625434

  18. Increasing maternal body mass index is associated with systemic inflammation in the mother and the activation of distinct placental inflammatory pathways.

    PubMed

    Aye, Irving L M H; Lager, Susanne; Ramirez, Vanessa I; Gaccioli, Francesca; Dudley, Donald J; Jansson, Thomas; Powell, Theresa L

    2014-06-01

    Obese pregnant women have increased levels of proinflammatory cytokines in maternal circulation and placental tissues. However, the pathways contributing to placental inflammation in obesity are largely unknown. We tested the hypothesis that maternal body mass index (BMI) was associated with elevated proinflammatory cytokines in maternal and fetal circulations and increased activation of placental inflammatory pathways. A total of 60 women of varying pre-/early pregnancy BMI, undergoing delivery by Cesarean section at term, were studied. Maternal and fetal (cord) plasma were collected for analysis of insulin, leptin, IL-1beta, IL-6, IL-8, monocyte chemoattractant protein (MCP) 1, and TNFalpha by multiplex ELISA. Activation of the inflammatory pathways in the placenta was investigated by measuring the phosphorylated and total protein expression of p38-mitogen-activated protein kinase (MAPK), c-Jun-N-terminal kinase (JNK)-MAPK, signal transducer-activated transcription factor (STAT) 3, caspase-1, IL-1beta, IkappaB-alpha protein, and p65 DNA-binding activity. To determine the link between activated placental inflammatory pathways and elevated maternal cytokines, cultured primary human trophoblast (PHT) cells were treated with physiological concentrations of insulin, MCP-1, and TNFalpha, and inflammatory signaling analyzed by Western blot. Maternal BMI was positively correlated with maternal insulin, leptin, MCP-1, and TNFalpha, whereas only fetal leptin was increased with BMI. Placental phosphorylation of p38-MAPK and STAT3, and the expression of IL-1beta protein, were increased with maternal BMI; phosphorylation of p38-MAPK was also correlated with birth weight. In contrast, placental NFkappaB, JNK and caspase-1 signaling, and fetal cytokine levels were unaffected by maternal BMI. In PHT cells, p38-MAPK was activated by MCP-1 and TNFalpha, whereas STAT3 phosphorylation was increased following TNFalpha treatment. Maternal BMI is associated with elevated maternal

  19. Immune complexes that contain HIV antigens activate peripheral blood T cells.

    PubMed

    Korolevskaya, L B; Shmagel, K V; Saidakova, E V; Shmagel, N G; Chereshnev, V A

    2016-07-01

    Uninfected donor T cells were treated in vitro by model immune complexes that contained either HIV or hepatitis C virus (HCV) antigens. Unlike HCV antigen-containing complexes, the immune complexes that contained HIV antigens have been shown to activate peripheral blood T cells of uninfected donors under in vitro conditions. Both the antiviral antibodies and HIV antigen were involved in the activation process. The unique properties of the immune complexes formed by HIV antigens and antiviral antibodies are believed to result from the virus-specific antibody properties and molecular conformation of the antigen-antibody complex. PMID:27595830

  20. Screening of Immune-Active Lactic Acid Bacteria

    PubMed Central

    Hwang, E-Nam; Kang, Sang-Mo; Kim, Mi-Jung

    2015-01-01

    The purpose of this study was to investigate the effect of lactic acid bacteria (LAB) cell wall extract on the proliferation and cytokine production of immune cells to select suitable probiotics for space food. Ten strains of LAB (Lactobacillus bulgaricus, L. paracasei, L. casei, L. acidophilus, L. plantarum, L. delbruekii, Lactococcus lactis, Streptococcus thermophilus, Bifidobacterium breve, and Pedicoccus pentosaceus) were sub-cultured and further cultured for 3 d to reach 7-10 Log colony-forming units (CFU)/mL prior to cell wall extractions. All LAB cell wall extracts failed to inhibit the proliferation of BALB/c mouse splenocytes or mesenteric lymphocytes. Most LAB cell wall extracts except those of L. plantarum and L. delbrueckii induced the proliferation of both immune cells at tested concentrations. In addition, the production of TH1 cytokine (IFN-γ) rather than that of TH2 cytokine (IL-4) was enhanced by LAB cell wall extracts. Of ten LAB extracts, four (from L. acidophilus, L. bulgaricus, L. casei, and S. thermophiles) promoted both cell proliferating and TH1 cytokine production. These results suggested that these LAB could be used as probiotics to maintain immunity and homeostasis for astronauts in extreme space environment and for general people in normal life. PMID:26761877

  1. [Immune defense is both stimulated and inhibited by physical activity].

    PubMed

    Malm, Christer; Celsing, Fredrik; Friman, Göran

    Physical exercise may enhance some and depress other immune functions. The biological importance of these changes is not fully elucidated. Acute endurance exercise results in a relatively large redistribution of leukocytes between circulating blood and other tissues, as well as an increase in circulating cytokines. Some of these changes have been related to energy metabolism. A temporal correlation has been observed between altered immune functions and resistance to infections. A post-exercise infection can be either the result of a pre-exercise, sub-clinical infection amplified by the performed work or a novel infection, acquired during a period of decreased immune function shortly after exercise. Animal experiments have demonstrated that the susceptibility to infections after exercise depends on exercise intensity and duration, type of pathogen and time of inoculation. Exercise before inoculation with some bacterial agents can enhance resistance to infection, while exercise during an ongoing viral or bacterial infection worsens symptoms and enhances the risk for complications. Most studies demonstrate a deleterious effect of physical exercise in conjunction with infectious episodes.

  2. Screening of Immune-Active Lactic Acid Bacteria.

    PubMed

    Hwang, E-Nam; Kang, Sang-Mo; Kim, Mi-Jung; Lee, Ju-Woon

    2015-01-01

    The purpose of this study was to investigate the effect of lactic acid bacteria (LAB) cell wall extract on the proliferation and cytokine production of immune cells to select suitable probiotics for space food. Ten strains of LAB (Lactobacillus bulgaricus, L. paracasei, L. casei, L. acidophilus, L. plantarum, L. delbruekii, Lactococcus lactis, Streptococcus thermophilus, Bifidobacterium breve, and Pedicoccus pentosaceus) were sub-cultured and further cultured for 3 d to reach 7-10 Log colony-forming units (CFU)/mL prior to cell wall extractions. All LAB cell wall extracts failed to inhibit the proliferation of BALB/c mouse splenocytes or mesenteric lymphocytes. Most LAB cell wall extracts except those of L. plantarum and L. delbrueckii induced the proliferation of both immune cells at tested concentrations. In addition, the production of TH1 cytokine (IFN-γ) rather than that of TH2 cytokine (IL-4) was enhanced by LAB cell wall extracts. Of ten LAB extracts, four (from L. acidophilus, L. bulgaricus, L. casei, and S. thermophiles) promoted both cell proliferating and TH1 cytokine production. These results suggested that these LAB could be used as probiotics to maintain immunity and homeostasis for astronauts in extreme space environment and for general people in normal life. PMID:26761877

  3. Maternal recasts and activity variations: a comparison of mother-child dyads involving children with and without SLI.

    PubMed

    Rezzonico, Stefano; de Weck, Geneviève; Salazar Orvig, Anne; da Silva Genest, Christine; Rahmati, Somayeh

    2014-04-01

    This study investigated maternal recast and the children's responses comparing dyads made up of a mother and a child with typical language development (TD) or a child with specific language impairment (SLI). More specifically, this article deals with the influence of the type of activity being carried out on the number and types of maternal recasts. A sample of 17 French-speaking children with SLI (age 5 to 7 years) matched with 17 TD same-age peers was observed in interaction with their mother during four different activities (joint reading, symbolic play, question guessing game and clue guessing game). The results showed that group and activity had an impact on the number and type of recasts. Mothers of children with SLI offered more recasts than mothers of TD children. The former preferred phonological recasts whereas the latter preferred lexical ones. Moreover, recasts were more frequently used in joint reading than in other activities. Regarding the children's responses, no significant difference was observed between the two groups. Children with SLI took up the maternal proposition more frequently after a lexical recast than after a recast of another type. The findings provide evidence for considering the features of the activities in clinical settings.

  4. Maternal and paternal parenting practices and their influence on children's adiposity, screen-time, diet and physical activity.

    PubMed

    Lloyd, Adam B; Lubans, David R; Plotnikoff, Ronald C; Collins, Clare E; Morgan, Philip J

    2014-08-01

    The primary aim of this study was to examine a range of potential behavioral and maternal/paternal correlates of adiposity in children. Secondary aims were to examine (a) correlates of screen-time, diet and physical activity and (b) if there were differences in maternal and paternal physical activity- and dietary-related parenting practices. Cross-sectional analysis was conducted using 70 families with children (59% boys (41/70), mean age 8.4 (±2.4) years). Parenting practices were measured using the Parenting Strategies for Eating and Activity Scale. Children's outcomes included: 7-day pedometry (physical activity), screen-time, percent energy from core foods (Food frequency questionnaire) and BMI z-score. Multiple regression models were generated to examine the associations between maternal and paternal parenting practices and children's variables. In the regression analyses, fathers' BMI (p < .01) and mothers' control (p < .001) were significantly associated with child weight status. Fathers' reinforcement (p < .01) was significantly associated with child physical activity. For screen-time, mothers' monitoring (p < .001) and child characteristics [age (p = .01), sex (p = .01), BMI z-score (p = .03)] were significant predictors. Mothers' parenting practices [limit setting (p = .01), reinforcement (p = .02)] and child screen-time (p = .02) were significantly associated with intake of core foods. Despite some similarities within families, three out of five parenting constructs were significantly different between mothers and fathers. Mothers and fathers have different parental influences on their children's weight status and lifestyle behaviors and both should be included in lifestyle interventions targeting children. A focus on maternal parenting specifically relating to screen-time and diet, and father's physical activity parenting and weight status may support their children in developing more healthy behaviors.

  5. Lactic acid bacteria activating innate immunity improve survival in bacterial infection model of silkworm.

    PubMed

    Nishida, Satoshi; Ono, Yasuo; Sekimizu, Kazuhisa

    2016-02-01

    Lactic acid bacteria (LAB) have been thought to be helpful for human heath in the gut as probiotics. It recently was noted that activity of LAB stimulating immune systems is important. Innate immune systems are conserved in mammals and insects. Silkworm has innate immunity in response to microbes. Microbe-associated molecular pattern (ex. peptidoglycan and β-glucan) induces a muscle contraction of silkworm larva. In this study, we established an efficient method to isolate lactic acid bacteria derived from natural products. We selected a highly active LAB to activate the innate immunity in silkworm by using the silkworm muscle contraction assay, as well. The assay revealed that Lactococcus lactis 11/19-B1 was highly active on the stimulation of the innate immunity in silkworm. L. lactis 11/19-B1 solely fermented milk with casamino acid and glucose. This strain would be a starter strain to make yogurt. Compared to commercially available yogurt LAB, L. lactis 11/19-B1 has higher activity on silkworm contraction. Silkworm normally ingested an artificial diet mixed with L. lactis 11/19-B1 or a yogurt fermented with L. lactis 11/19-B1. Interestingly, silkworms that ingested the LAB showed tolerance against the pathogenicity of Pseudomonas aeruginosa. These data suggest that Lactococcus lactis 11/19-B1 would be expected to be useful for making yogurt and probiotics to activate innate immunity. PMID:26971556

  6. Sexually dimorphic effects of neonatal immune system activation with lipopolysaccharide on the behavioural response to a homotypic adult immune challenge.

    PubMed

    Tenk, Christine M; Kavaliers, Martin; Ossenkopp, Klaus-Peter

    2008-01-01

    Research has shown that acute immune activation during the early postnatal period with the Gram-negative endotoxin, lipopolysaccharide (LPS), alters a variety of physiological and behavioural processes in the adult animal. For example, neonatal LPS exposure affects disease susceptibility later in life, though these effects appear to be modulated by time of exposure, sex, and immune stimulus. The current study examined sex differences in the effect of neonatal LPS treatment on the locomotor activity response to adult LPS administration. Male and female Long-Evans rats were treated systemically with either LPS (50 microg/kg) or saline (0.9%) on postnatal days 3 and 5. Later in adulthood (postnatal day 92), all animals were subjected to an adult LPS challenge and were injected (i.p.) with 200 microg/kg LPS. Two hours after injection, animals were placed in a non-novel open-field and locomotor activity was assessed for 30 min. Body weights were determined both at the time of injection and 24h later to examine LPS-induced weight loss. Adult males treated neonatally with LPS exhibited significantly less horizontal and vertical activity in response to the LPS challenge relative to males treated neonatally with saline. This effect was not observed in females. Thus, the current study provides important evidence of sexual dimorphism in the long-term effects of neonatal LPS exposure on the responses to an adult homotypic immune challenge in rats. These findings have potential clinical significance given that neonatal exposure to pathogens is a fairly common occurrence and Gram-negative bacteria are a common cause of neonatal bacterial infections.

  7. Activism: working to reduce maternal mortality through civil society and health professional alliances in sub-Saharan Africa.

    PubMed

    Ray, Sunanda; Madzimbamuto, Farai; Fonn, Sharon

    2012-06-01

    Partnerships between civil society groups campaigning for reproductive and human rights, health professionals and others could contribute more to the strengthening of health systems needed to bring about declines in maternal deaths in Africa. The success of the HIV treatment literacy model developed by the Treatment Action Campaign in South Africa provides useful lessons for activism on maternal mortality, especially the combination of a right-to-health approach with learning and capacity building, community networking, popular mobilisation and legal action. This paper provides examples of these from South Africa, Botswana, Kenya and Uganda. Confidential enquiries into maternal deaths can be powerful instruments for change if pressure to act on their recommendations is brought to bear. Shadow reports presented during UN human rights country assessments can be used in a similar way. Public protests and demonstrations over avoidable deaths have succeeded in drawing attention to under-resourced services, shortages of supplies, including blood for transfusion, poor morale among staff, and lack of training and supervision. Activists could play a bigger role in holding health services, governments, and policy-makers accountable for poor maternity services, developing user-friendly information materials for women and their families, and motivating appropriate human resources strategies. Training and support for patients' groups, in how to use health facility complaints procedures is also a valuable strategy. PMID:22789081

  8. Activism: working to reduce maternal mortality through civil society and health professional alliances in sub-Saharan Africa.

    PubMed

    Ray, Sunanda; Madzimbamuto, Farai; Fonn, Sharon

    2012-06-01

    Partnerships between civil society groups campaigning for reproductive and human rights, health professionals and others could contribute more to the strengthening of health systems needed to bring about declines in maternal deaths in Africa. The success of the HIV treatment literacy model developed by the Treatment Action Campaign in South Africa provides useful lessons for activism on maternal mortality, especially the combination of a right-to-health approach with learning and capacity building, community networking, popular mobilisation and legal action. This paper provides examples of these from South Africa, Botswana, Kenya and Uganda. Confidential enquiries into maternal deaths can be powerful instruments for change if pressure to act on their recommendations is brought to bear. Shadow reports presented during UN human rights country assessments can be used in a similar way. Public protests and demonstrations over avoidable deaths have succeeded in drawing attention to under-resourced services, shortages of supplies, including blood for transfusion, poor morale among staff, and lack of training and supervision. Activists could play a bigger role in holding health services, governments, and policy-makers accountable for poor maternity services, developing user-friendly information materials for women and their families, and motivating appropriate human resources strategies. Training and support for patients' groups, in how to use health facility complaints procedures is also a valuable strategy.

  9. Adolescent adrenocortical activity and adiposity: differences by sex and exposure to early maternal depression.

    PubMed

    Ruttle, Paula L; Klein, Marjorie H; Slattery, Marcia J; Kalin, Ned H; Armstrong, Jeffrey M; Essex, Marilyn J

    2014-09-01

    Prior research has linked either basal cortisol levels or stress-induced cortisol responses to adiposity; however, it remains to be determined whether these distinct cortisol measures exert joint or independent effects. Further, it is unclear how they interact with individual and environmental characteristics to predict adiposity. The present study aims to address whether morning cortisol levels and cortisol responses to a psychosocial stressor independently and/or interactively influence body mass index (BMI) in 218 adolescents (117 female) participating in a longitudinal community study, and whether associations are moderated by sex and exposure to early maternal depression. Reports of maternal depressive symptoms were obtained in infancy and preschool. Salivary cortisol measures included a longitudinal morning cortisol measure comprising sampling points across ages 11, 13, 15, and 18 and measures of stress-induced cortisol responses assessed via the Trier Social Stress Test (TSST) at age 18. Lower morning cortisol and higher TSST cortisol reactivity independently predicted higher age 18 BMI. Morning cortisol also interacted with sex and exposure to early maternal depression to predict BMI. Specifically, girls exposed to lower levels of early maternal depression displayed a strong negative morning cortisol-BMI association, and girls exposed to higher levels of maternal depression demonstrated a weaker negative association. Among boys, those exposed to lower levels of maternal depression displayed no association, while those exposed to higher levels of maternal depression displayed a negative morning cortisol-BMI association. Results point to the independent, additive effects of morning and reactive cortisol in the prediction of BMI and suggest that exposure to early maternal depression may exert sexually dimorphic effects on normative cortisol-BMI associations.

  10. Role of lymphatic vessels in tumor immunity: passive conduits or active participants?

    PubMed

    Lund, Amanda W; Swartz, Melody A

    2010-09-01

    Research in lymphatic biology and cancer immunology may soon intersect as emerging evidence implicates the lymphatics in the progression of chronic inflammation and autoimmunity as well as in tumor metastasis and immune escape. Like the blood vasculature, the lymphatic system comprises a highly dynamic conduit system that regulates fluid homeostasis, antigen transport and immune cell trafficking, which all play important roles in the progression and resolution of inflammation, autoimmune diseases, and cancer. This review presents emerging evidence that lymphatic vessels are active modulators of immunity, perhaps fine-tuning the response to adjust the balance between peripheral tolerance and immunity. This suggests that the tumor-associated lymphatic vessels and draining lymph node may be important in tumor immunity which in turn governs metastasis.

  11. A mathematical model of immune activation with a unified self-nonself concept.

    PubMed

    Khailaie, Sahamoddin; Bahrami, Fariba; Janahmadi, Mahyar; Milanez-Almeida, Pedro; Huehn, Jochen; Meyer-Hermann, Michael

    2013-01-01

    The adaptive immune system reacts against pathogenic nonself, whereas it normally remains tolerant to self. The initiation of an immune response requires a critical antigen(Ag)-stimulation and a critical number of Ag-specific T cells. Autoreactive T cells are not completely deleted by thymic selection and partially present in the periphery of healthy individuals that respond in certain physiological conditions. A number of experimental and theoretical models are based on the concept that structural differences discriminate self from nonself. In this article, we establish a mathematical model for immune activation in which self and nonself are not distinguished. The model considers the dynamic interplay of conventional T cells, regulatory T cells (Tregs), and IL-2 molecules and shows that the renewal rate ratio of resting Tregs to naïve T cells as well as the proliferation rate of activated T cells determine the probability of immune stimulation. The actual initiation of an immune response, however, relies on the absolute renewal rate of naïve T cells. This result suggests that thymic selection reduces the probability of autoimmunity by increasing the Ag-stimulation threshold of self reaction which is established by selection of a low number of low-avidity autoreactive T cells balanced with a proper number of Tregs. The stability analysis of the ordinary differential equation model reveals three different possible immune reactions depending on critical levels of Ag-stimulation: a subcritical stimulation, a threshold stimulation inducing a proper immune response, and an overcritical stimulation leading to chronic co-existence of Ag and immune activity. The model exhibits oscillatory solutions in the case of persistent but moderate Ag-stimulation, while the system returns to the homeostatic state upon Ag clearance. In this unifying concept, self and nonself appear as a result of shifted Ag-stimulation thresholds which delineate these three regimes of immune

  12. Effects of maternal natural (RRR alpha-tocopherol acetate) or synthetic (all-rac alpha-tocopherol acetate) vitamin E supplementation on suckling calf performance, colostrum immunoglobulin G, and immune function.

    PubMed

    Horn, M J; Van Emon, M L; Gunn, P J; Eicher, S D; Lemenager, R P; Burgess, J; Pyatt, N; Lake, S L

    2010-09-01

    The objective of this study was to determine the effects of maternally supplemented natural- or synthetic-source vitamin E on suckling calf performance and immune response. In a 2-yr study, one hundred fifty-two 2- and 3-yr-old, spring-calving, Angus-cross beef cows were blocked by age, BW, and BCS into 1 of 3 isocaloric, corn-based dietary supplements containing 1) no additional vitamin E (CON), 2) 1,000 IU/d of synthetic-source vitamin E (SYN), or 3) 1,000 IU/d of natural-source vitamin E (NAT). Maternal supplementation began approximately 6 wk prepartum and continued until the breeding season. Colostrum from cows and blood from calves was collected 24 h postpartum for analysis of IgG concentration as an indicator of passive transfer and circulating alpha-tocopherol concentration. At 19 d of age, blood was collected from calves to determine the expression of CD14 and CD18 molecules on leukocytes. At 21 and 35 d of age, humoral immune response was measured by a subcutaneous injection, in the neck, with ovalbumin (20 mg; OVA) and blood samples collected weekly until d 63 of age to determine antibodies produced against OVA. At d 63 of age, calves were administered an intradermal injection of OVA (1 mg) in the neck to assess cell-mediated immunity, which was determined on d 65 of age by measuring nodule size with calipers. Circulating alpha-tocopherol concentrations were increased at both 24 h (P = 0.001) and at the day of initial OVA challenge (P < 0.001) in SYN and NAT compared with CON calves. No differences were detected (P > 0.05) for calf birth BW, ADG, or weaning BW. There were no differences (P > 0.05) in calf serum total IgG or cow colostrum total IgG at 24 h or presence of CD14 and CD18 receptors at d 19 of age. The NAT calves had a greater antigen response to OVA at d 63 than SYN calves (P = 0.01; treatment x day interaction). As an indicator of cell-mediated immunity to OVA, nodule size at 65 d of age was not affected (P = 0.92) by maternal dietary

  13. Decline of maternal antibodies to plague in Norway rats.

    PubMed

    Williams, J E; Eisenberg, G H; Cavanaugh, D C

    1977-02-01

    The decline of maternal antibodies to the fraciton I antigen of Yersinia pestis was investigated in newly weaned Rattus norvegicus obtained from dams vaccinated with strain EV76(51F) of Y. pestis. IHA titre decreased by 50% each 7-3 days and CF titre declined 50% each 10-0 days in young rats. An analysis of available data indicated that maternal IHA and CF antibodies could persist to 3 months of age. Therefore, positive serologic reactions in young R. norvegicus, detected in the course of serological surveys, could be the result either of active immunization after exposure to the plague bacillus or of transient passive immunization (i.e. maternal antibody). PMID:264498

  14. Mechanisms of immune system activation in mammalians by small interfering RNA (siRNA).

    PubMed

    Mansoori, Behzad; Mohammadi, Ali; Shir Jang, Solmaz; Baradaran, Behzad

    2016-11-01

    RNA interference (RNAi) guided by small interfering RNAs (siRNA), because of its potential to target and silence the expression of specific genes is utilized as an effective tool in a variety of biological applications. RNAi guided by siRNAs is a powerful tool to attain gene silencing in mammalian cells. One of the features which make siRNA as an amazing biological tool is extremely specific knockdown of target genes by degradation of analogous mRNAs. However, various non-specific effects limit the use of RNAi including the activation of innate immunity and inhibition of inadvertent target genes. One of the most common non-specific effects is inducing the innate immune system including cytoplasmic and endosomal activation of innate immune system, potentially offending the single in mammals. This activation is mainly interceded by immune cells, regularly through a Toll-like receptor (TLR) pathway. The siRNA sequence association of these pathways changes with the sort and position of the TLR involved. In contrast, non-immune cell activation can also arise generally siRNAs which enter into cytoplasm interacting with cytoplasmic RNA sensors such as retinoic acid-inducible gene I. Here, we explain the off-target effects of siRNAs that activate innate immune system and methods to alleviate them, to help enable impressive application of this exciting technology, Also we bold the aspect of molecular strategies permitting the design of therapeutic siRNAs with minute off-target effects.

  15. Lgt Processing Is an Essential Step in Streptococcus suis Lipoprotein Mediated Innate Immune Activation

    PubMed Central

    Wichgers Schreur, Paul J.; Rebel, Johanna M. J.; Smits, Mari A.; van Putten, Jos P. M.; Smith, Hilde E.

    2011-01-01

    Background Streptococcus suis causes invasive infections in pigs and occasionally in humans. The host innate immune system plays a major role in counteracting S. suis infections. The main components of S. suis able to activate the innate immune system likely include cell wall constituents that may be released during growth or after cell wall integrity loss, however characterization of these components is still limited. Methology/Principal Findings A concentrated very potent innate immunity activating supernatant of penicillin-treated S. suis was SDS-PAGE fractionated and tested for porcine peripheral blood mononucleated cell (PBMC) stimulating activity using cytokine gene transcript analysis. More than half of the 24 tested fractions increased IL-1β and IL-8 cytokine gene transcript levels in porcine PBMCs. Mass spectrometry of the active fractions indicated 24 proteins including 9 lipoproteins. Genetic inactivation of a putative prolipoprotein diacylglyceryl transferase (Lgt) gene resulted in deficient lipoprotein synthesis as evidenced by palmitate labeling. The Lgt mutant showed strongly reduced activation of porcine PBMCs, indicating that lipoproteins are dominant porcine PBMC activating molecules of S. suis. Conclusion/Significance This study for the first time identifies and characterizes lipoproteins of S. suis as major activators of the innate immune system of the pig. In addition, we provide evidence that Lgt processing of lipoproteins is required for lipoprotein mediated innate immune activation. PMID:21811583

  16. Evidence that FcRn mediates the transplacental passage of maternal IgE in the form of IgG anti-IgE/IgE immune complexes

    PubMed Central

    Bundhoo, Arvin; Paveglio, Sara; Rafti, Ektor; Dhongade, Ashish; Blumberg, Richard S.; Matson, Adam P.

    2015-01-01

    Background The mechanism(s) responsible for acquisition of maternal antibody isotypes other than IgG are not fully understood. This uncertainty is a major reason underlying the continued controversy regarding whether cord blood (CB) IgE originates in the mother or fetus. Objective To investigate the capacity of maternal IgE to be transported across the placenta in the form of IgG anti-IgE/IgE immune complexes (ICs) and to determine the role of the neonatal Fc receptor (FcRn) in mediating this process. Methods Maternal and CB serum concentrations of IgE, IgG anti-IgE, and IgG anti-IgE/IgE ICs were determined in a cohort of allergic and non-allergic mother/infant dyads. Madin-Darby Canine Kidney (MDCK) cells stably transfected with human FcRn were used to study the binding and transcytosis of IgE in the form of IgG anti-IgE/IgE ICs. Results Maternal and CB serum concentrations of IgG anti-IgE/IgE ICs were highly correlated, regardless of maternal allergic status. IgG anti-IgE/IgE ICs generated in vitro bound strongly to FcRn-expressing MDCK cells and were transcytosed in an FcRn-dependent manner. Conversely, monomeric IgE did not bind to FcRn and was not transcytosed. IgE was detected in solutions of transcytosed IgG anti-IgE/IgE ICs, even though essentially all the IgE remained in complex form. Similarly, the majority of IgE in CB sera was found to be complexed to IgG. Conclusions and Clinical Relevance These data indicate that human FcRn facilitates the transepithelial transport of IgE in the form of IgG anti-IgE/IgE ICs. They also strongly suggest that the majority of IgE in CB sera is the result of FcRn-mediated transcytosis of maternal-derived IgG anti-IgE/IgE ICs. These findings challenge the widespread perception that maternal IgE does not cross the placenta. Measuring maternal or CB levels of IgG anti-IgE/IgE ICs may be a more accurate predictor of allergic risk. PMID:25652137

  17. A maternal high-fat diet modulates fetal SIRT1 histone and protein deacetylase activity in nonhuman primates

    PubMed Central

    Suter, Melissa A.; Chen, Aishe; Burdine, Marie S.; Choudhury, Mahua; Harris, R. Alan; Lane, Robert H.; Friedman, Jacob E.; Grove, Kevin L.; Tackett, Alan J.; Aagaard, Kjersti M.

    2012-01-01

    In nonhuman primates, we previously demonstrated that a maternal high-fat diet (MHFD) induces fetal nonalcoholic fatty liver disease (NAFLD) and alters the fetal metabolome. These changes are accompanied by altered acetylation of histone H3 (H3K14ac). However, the mechanism behind this alteration in acetylation remains unknown. As SIRT1 is both a lysine deacetylase and a crucial sensor of cellular metabolism, we hypothesized that SIRT1 may be involved in fetal epigenomic alterations. Here we show that in utero exposure to a MHFD, but not maternal obesity per se, increases fetal H3K14ac with concomitant decreased SIRT1 expression and diminished in vitro protein and histone deacetylase activity. MHFD increased H3K14ac and DBC1-SIRT1 complex formation in fetal livers, both of which were abrogated with diet reversal despite persistent maternal obesity. Moreover, MHFD was associated with altered expression of known downstream effectors deregulated in NAFLD and modulated by SIRT1 (e.g., PPARΑ, PPARG, SREBF1, CYP7A1, FASN, and SCD). Finally, ex vivo purified SIRT1 retains deacetylase activity on an H3K14ac peptide substrate with preferential activity toward acetylated histone H3; mutagenesis of the catalytic domain of SIRT1 (H363Y) abrogates H3K14ac deacetylation. Our data implicate SIRT1 as a likely molecular mediator of the fetal epigenome and metabolome under MHFD conditions.—Suter, M. A., Chen, A., Burdine, M. S., Choudhury, M., Harris, R. A., Lane, R. H., Friedman, J. E., Grove, K. L., Tackett, A. J., Aagaard, K. M. A maternal high-fat diet modulates fetal SIRT1 histone and protein deacetylase activity in nonhuman primates. PMID:22982377

  18. Persistently Active Microbial Molecules Prolong Innate Immune Tolerance In Vivo

    PubMed Central

    Lu, Mingfang; Varley, Alan W.; Munford, Robert S.

    2013-01-01

    Measures that bolster the resolution phase of infectious diseases may offer new opportunities for improving outcome. Here we show that inactivation of microbial lipopolysaccharides (LPS) can be required for animals to recover from the innate immune tolerance that follows exposure to Gram-negative bacteria. When wildtype mice are exposed to small parenteral doses of LPS or Gram-negative bacteria, their macrophages become reprogrammed (tolerant) for a few days before they resume normal function. Mice that are unable to inactivate LPS, in contrast, remain tolerant for several months; during this time they respond sluggishly to Gram-negative bacterial challenge, with high mortality. We show here that prolonged macrophage reprogramming is maintained in vivo by the persistence of stimulatory LPS molecules within the cells' in vivo environment, where naïve cells can acquire LPS via cell-cell contact or from the extracellular fluid. The findings provide strong evidence that inactivation of a stimulatory microbial molecule can be required for animals to regain immune homeostasis following parenteral exposure to bacteria. Measures that disable microbial molecules might enhance resolution of tissue inflammation and help restore innate defenses in individuals recovering from many different infectious diseases. PMID:23675296

  19. Platelet activating factor receptor binding plays a critical role in jet fuel-induced immune suppression.

    PubMed

    Ramos, Gerardo; Kazimi, Nasser; Nghiem, Dat X; Walterscheid, Jeffrey P; Ullrich, Stephen E

    2004-03-15

    Applying military jet fuel (JP-8) or commercial jet fuel (Jet-A) to the skin of mice suppresses the immune response in a dose-dependent manner. The release of biological response modifiers, particularly prostaglandin E2 (PGE2), is a critical step in activating immune suppression. Previous studies have shown that injecting selective cyclooxygenase-2 inhibitors into jet fuel-treated mice blocks immune suppression. Because the inflammatory phospholipid mediator, platelet-activating factor (PAF), up-regulates cyclooxygenase-2 production and PGE2 synthesis by keratinocytes, we tested the hypothesis that PAF-receptor binding plays a role in jet fuel-induced immune suppression. Treating keratinocyte cultures with PAF and/or jet fuel (JP-8 and Jet-A) stimulates PGE2 secretion. Jet fuel-induced PGE2 production was suppressed by treating the keratinocytes with specific PAF-receptor antagonists. Injecting mice with PAF, or treating the skin of the mice with JP-8, or Jet-A, induced immune suppression. Jet fuel-induced immune suppression was blocked when the jet fuel-treated mice were injected with PAF-receptor antagonists before treatment. Jet fuel treatment has been reported to activate oxidative stress and treating the mice with anti-oxidants (Vitamins C, or E or beta-hydroxy toluene), before jet fuel application, interfered with immune suppression. These findings confirm previous studies showing that PAF-receptor binding can modulate immune function. Furthermore, they suggest that PAF-receptor binding may be an early event in the induction of immune suppression by immunotoxic environmental agents that target the skin. PMID:15020195

  20. Methods to Evaluate the Antitumor Activity of Immune Checkpoint Inhibitors in Preclinical Studies.

    PubMed

    Allard, Bertrand; Allard, David; Stagg, John

    2016-01-01

    Immune checkpoint inhibitors (ICI) are a new class of drugs characterized by their ability to enhance antitumor immune responses through the blockade of critical cell surface receptors involved in the maintenance of peripheral tolerance. The recent approval of ICI targeting CTLA-4 or PD-1 for the treatment of cancer constitutes a major breakthrough in the field of oncology and demonstrates the potential of immune-mediated therapies in achieving durable cancer remissions. The identification of new immune regulatory pathways that could be targeted to reactivate or boost antitumor immunity is now a very active field of research. In this context, the use of syngeneic mouse models and immune monitoring techniques are the cornerstone of proof-of-concept studies. In this chapter, we describe the general methodology to evaluate antitumor activity of ICI in immunocompetent mice. We outline protocols to reliably establish tumors in mice and generate lung metastasis through tail vein injections with the aim of testing the efficacy of ICI. We also present methods to analyze the composition of the tumor immune-infiltrate by multicolor flow cytometry. PMID:27581021

  1. Zinc deficiency enhanced inflammatory response by increasing immune cell activation and inducing IL6 promoter demethylation

    PubMed Central

    Wong, Carmen P.; Rinaldi, Nicole A.; Ho, Emily

    2015-01-01

    Scope Zinc deficiency results in immune dysfunction and promotes systemic inflammation. The objective of this study was to examine the effects of zinc deficiency on cellular immune activation and epigenetic mechanisms that promote inflammation. This work is potentially relevant to the aging population given that age-related immune defects, including chronic inflammation, coincide with declining zinc status. Methods and results An in vitro cell culture system and the aged mouse model were used to characterize immune activation and DNA methylation profiles that may contribute to the enhanced proinflammatory response mediated by zinc deficiency. Zinc deficiency up-regulated cell activation markers ICAM1, MHC class II, and CD86 in THP1 cells, that coincided with increased IL1β and IL6 responses following LPS stimulation. A decreased zinc status in aged mice was similarly associated with increased ICAM1 and IL6 gene expression. Reduced IL6 promoter methylation was observed in zinc deficient THP1 cells, as well as in aged mice and human lymphoblastoid cell lines derived from aged individuals. Conclusion Zinc deficiency induced inflammatory response in part by eliciting aberrant immune cell activation and altered promoter methylation. Our results suggested potential interactions between zinc status, epigenetics, and immune function, and how their dysregulation could contribute to chronic inflammation. PMID:25656040

  2. Possible activation of auto-immune thyroiditis from continuous subcutaneous infusion of genapol-containing insulin.

    PubMed

    Chantelau, E

    2000-09-01

    A case of a type 1 diabetic woman with auto-immune thyroiditis is reported, in whom repeated exposure to insulin containing Genapol(R) (polyethylen-polypropylenglycol) over 3 years reproducibly parallels with an increase of serum TSH (thyroid-stimulating hormone) above the normal limit. Previously, adverse effects of Genapol(R) insulin have been related to its intraperitoneal application, and thought to be restricted to anti-insulin-immunity; activating effects on thyroid auto-immunity have been repeatedly disputed. We suggest that Genapol(R) insulin should be replaced by other insulin preparations with a better safety record.

  3. Spatiotemporal Regulation of Hsp90-Ligand Complex Leads to Immune Activation.

    PubMed

    Tamura, Yasuaki; Yoneda, Akihiro; Takei, Norio; Sawada, Kaori

    2016-01-01

    Although heat shock proteins (HSPs) primarily play a pivotal role in the maintenance of cellular homeostasis while reducing extracellular as well as intracellular stresses, their role in immunologically relevant scenarios, including activation of innate immunity as danger signals, antitumor immunity, and autoimmune diseases, is now gaining much attention. The most prominent feature of HSPs is that they function both in their own and as an HSP-ligand complex. We here show as a unique feature of extracellular HSPs that they target chaperoned molecules into a particular endosomal compartment of dendritic cells, thereby inducing innate and adaptive immune responses via spatiotemporal regulation. PMID:27252703

  4. Spatiotemporal Regulation of Hsp90–Ligand Complex Leads to Immune Activation

    PubMed Central

    Tamura, Yasuaki; Yoneda, Akihiro; Takei, Norio; Sawada, Kaori

    2016-01-01

    Although heat shock proteins (HSPs) primarily play a pivotal role in the maintenance of cellular homeostasis while reducing extracellular as well as intracellular stresses, their role in immunologically relevant scenarios, including activation of innate immunity as danger signals, antitumor immunity, and autoimmune diseases, is now gaining much attention. The most prominent feature of HSPs is that they function both in their own and as an HSP–ligand complex. We here show as a unique feature of extracellular HSPs that they target chaperoned molecules into a particular endosomal compartment of dendritic cells, thereby inducing innate and adaptive immune responses via spatiotemporal regulation. PMID:27252703

  5. Maternal microchimerism

    PubMed Central

    Ye, Jody; Vives-Pi, Marta; Gillespie, Kathleen M

    2014-01-01

    Increased levels of non-inherited maternal HLA alleles have been detected in the periphery of children with type 1 diabetes and an increased frequency of maternal cells have been identified in type 1 diabetes pancreas. It is now clear that the phenotype of these cells is pancreatic,1 supporting the hypothesis that maternal cells in human pancreas are derived from multipotent maternal progenitors. Here we hypothesize how increased levels of maternal cells could play a role in islet autoimmunity. PMID:25093746

  6. Modern Radiotherapy Concepts and the Impact of Radiation on Immune Activation

    PubMed Central

    Deloch, Lisa; Derer, Anja; Hartmann, Josefin; Frey, Benjamin; Fietkau, Rainer; Gaipl, Udo S.

    2016-01-01

    Even though there is extensive research carried out in radiation oncology, most of the clinical studies focus on the effects of radiation on the local tumor tissue and deal with normal tissue side effects. The influence of dose fractionation and timing particularly with regard to immune activation is not satisfactorily investigated so far. This review, therefore, summarizes current knowledge on concepts of modern radiotherapy (RT) and evaluates the potential of RT for immune activation. Focus is set on radiation-induced forms of tumor cell death and consecutively the immunogenicity of the tumor cells. The so-called non-targeted, abscopal effects can contribute to anti-tumor responses in a specific and systemic manner and possess the ability to target relapsing tumor cells as well as metastases. The impact of distinct RT concepts on immune activation is outlined and pre-clinical evidence and clinical observations on RT-induced immunity will be discussed. Knowledge on the radiosensitivity of immune cells as well as clinical evidence for enhanced immunity after RT will be considered. While stereotactic ablative body radiotherapy seem to have a beneficial outcome over classical RT fractionation in pre-clinical animal models, in vitro model systems suggest an advantage for classical fractionated RT for immune activation. Furthermore, the optimal approach may differ based on the tumor site and/or genetic signature. These facts highlight that clinical trials are urgently needed to identify whether high-dose RT is superior to induce anti-tumor immune responses compared to classical fractionated RT and in particular how the outcome is when RT is combined with immunotherapy in selected tumor entities. PMID:27379203

  7. Modern Radiotherapy Concepts and the Impact of Radiation on Immune Activation.

    PubMed

    Deloch, Lisa; Derer, Anja; Hartmann, Josefin; Frey, Benjamin; Fietkau, Rainer; Gaipl, Udo S

    2016-01-01

    Even though there is extensive research carried out in radiation oncology, most of the clinical studies focus on the effects of radiation on the local tumor tissue and deal with normal tissue side effects. The influence of dose fractionation and timing particularly with regard to immune activation is not satisfactorily investigated so far. This review, therefore, summarizes current knowledge on concepts of modern radiotherapy (RT) and evaluates the potential of RT for immune activation. Focus is set on radiation-induced forms of tumor cell death and consecutively the immunogenicity of the tumor cells. The so-called non-targeted, abscopal effects can contribute to anti-tumor responses in a specific and systemic manner and possess the ability to target relapsing tumor cells as well as metastases. The impact of distinct RT concepts on immune activation is outlined and pre-clinical evidence and clinical observations on RT-induced immunity will be discussed. Knowledge on the radiosensitivity of immune cells as well as clinical evidence for enhanced immunity after RT will be considered. While stereotactic ablative body radiotherapy seem to have a beneficial outcome over classical RT fractionation in pre-clinical animal models, in vitro model systems suggest an advantage for classical fractionated RT for immune activation. Furthermore, the optimal approach may differ based on the tumor site and/or genetic signature. These facts highlight that clinical trials are urgently needed to identify whether high-dose RT is superior to induce anti-tumor immune responses compared to classical fractionated RT and in particular how the outcome is when RT is combined with immunotherapy in selected tumor entities. PMID:27379203

  8. Activation of NLRC4 downregulates TLR5-mediated antibody immune responses against flagellin

    PubMed Central

    Li, Wei; Yang, Jingyi; Zhang, Ejuan; Zhong, Maohua; Xiao, Yang; Yu, Jie; Zhou, Dihan; Cao, Yuan; Yang, Yi; Li, Yaoming; Yan, Huimin

    2016-01-01

    Bacterial flagellin is a unique pathogen-associated molecular pattern (PAMP), which can be recognized by surface localized Toll-like receptor 5 (TLR5) and the cytosolic NOD-like receptor (NLR) protein 4 (NLRC4) receptors. Activation of the TLR5 and/or NLRC4 signaling pathways by flagellin and the resulting immune responses play important roles in anti-bacterial immunity. However, it remains unclear how the dual activities of flagellin that activate the TLR5 and/or NLRC4 signaling pathways orchestrate the immune responses. In this study, we assessed the effects of flagellin and its mutants lacking the ability to activate TLR5 and NLRC4 alone or in combination on the adaptive immune responses against flagellin. Flagellin that was unable to activate NLRC4 induced a significantly higher antibody response than did wild-type flagellin. The increased antibody response could be eliminated when macrophages were depleted in vivo. The activation of NLRC4 by flagellin downregulated the flagellin-induced and TLR5-mediated immune responses against flagellin. PMID:25914934

  9. Proinflammatory Activity and the Sensitization of Depressive-Like Behavior during Maternal Separation

    PubMed Central

    Hennessy, Michael B.; Paik, Kristopher D.; Caraway, Jessica D.; Schiml, Patricia A.; Deak, Terrence

    2011-01-01

    When guinea pig pups are isolated for a few hours in a novel environment, they exhibit a distinctive passive behavioral response that appears to be mediated by proinflammatory activity. Recently, we observed that pups separated on two consecutive days show an enhanced (sensitized) passive response on the second day. In Experiment 1, pups receiving intracerebroventricular infusion of 50 ng of the anti-inflammatory cytokine Interleukin-10 prior to a first separation failed to show a sensitized behavioral response to separation the next day. In Experiment 2, pups separated on Days 1 and 2, or just 2, showed an increase in passive responding during separation on Day 5. Pups injected with the bacterial antigen lipopolysacchride (LPS; 75μg/kg body weight, intraperitoneal) prior to separation on Day 1 showed an increase in passive behavior several days later not shown by pups injected with saline prior to Day 1 separation. However, injection of LPS without separation on the first day did not enhance responding during an initial separation on the second day. These results suggest that immune activation is necessary, but not sufficient, to account for the sensitization of passive behavior of isolated guinea pig pups the following day, that boosting proinflammatory activity during an initial separation may promote sensitization several days later, and that the sensitized response persists for at least several days. PMID:21500883

  10. The Mitochondria-Regulated Immune Pathway Activated in the C. elegans Intestine Is Neuroprotective.

    PubMed

    Chikka, Madhusudana Rao; Anbalagan, Charumathi; Dvorak, Katherine; Dombeck, Kyle; Prahlad, Veena

    2016-08-30

    Immunological mediators that originate outside the nervous system can affect neuronal health. However, their roles in neurodegeneration remain largely unknown. Here, we show that the p38MAPK-mediated immune pathway activated in intestinal cells of Caenorhabditis elegans upon mitochondrial dysfunction protects neurons in a cell-non-autonomous fashion. Specifically, mitochondrial complex I dysfunction induced by rotenone activates the p38MAPK/CREB/ATF-7-dependent innate immune response pathway in intestinal cells of C. elegans. Activation of p38MAPK in the gut is neuroprotective. Enhancing the p38MAPK-mediated immune pathway in intestinal cells alone suppresses rotenone-induced dopaminergic neuron loss, while downregulating it in the intestine exacerbates neurodegeneration. The p38MAPK/ATF-7 immune pathway modulates autophagy and requires autophagy and the PTEN-induced putative kinase PINK-1 for conferring neuroprotection. Thus, mitochondrial damage induces the clearance of mitochondria by the immune pathway, protecting the organism from the toxic effects of mitochondrial dysfunction. We propose that mitochondria are subject to constant surveillance by innate immune mechanisms.

  11. Food Intolerance: Immune Activation Through Diet-associated Stimuli in Chronic Disease.

    PubMed

    Pietschmann, Nicole

    2015-01-01

    The immune response is a very complex interplay of specific and nonspecific branches that have evolved to distinguish between nondangerous and dangerous or nontolerated factors. In the past, research has focused on the specific immune system much more than the host's innate defense. Studies have shown that a key component of the immune response involves activation of the inflammasome. A direct relationship between the presence of the inflammasome and the onset of disease has already been characterized for a variety of chronic and food-related diseases, including arthrosclerosis, metabolic syndrome, and chronic bowel diseases, such as Crohn's disease and ulcerative colitis. The leukocyte activation (ALCAT test), an immunological blood test for food intolerance reactions, is ideal to identify and eliminate individual food stimuli that may act as triggers for the cellular nonspecific immune response. Although the test is not diagnostic, studies have established that it can be a useful screening tool for the identification of foreign substances that may trigger immune cell activation, particularly of neutrophils, leading to inflammatory disorders. The ALCAT test, coupled with a targeted diet that is individually tailored according to the test's results, may support immune homeostasis and provide a valuable complementary approach for therapy and overall health.

  12. RAC1 activation drives pathologic interactions between the epidermis and immune cells

    PubMed Central

    Winge, Mårten C.G.; Ohyama, Bungo; Dey, Clara N.; Boxer, Lisa M.; Li, Wei; Ehsani-Chimeh, Nazanin; Truong, Allison K.; Wu, Diane; Armstrong, April W.; Makino, Teruhiko; Davidson, Matthew; Starcevic, Daniela; Nguyen, Ngon T.; Hashimoto, Takashi; Homey, Bernard; Khavari, Paul A.; Bradley, Maria; Waterman, Elizabeth A.; Marinkovich, M. Peter

    2016-01-01

    Interactions between the epidermis and the immune system govern epidermal tissue homeostasis. These epidermis-immune interactions are altered in the inflammatory disease psoriasis; however, the pathways that underlie this aberrant immune response are not well understood. Here, we determined that Ras-related C3 botulinum toxin substrate 1 (RAC1) is a key mediator of epidermal dysfunction. RAC1 activation was consistently elevated in psoriatic epidermis and primary psoriatic human keratinocytes (PHKCs) exposed to psoriasis-related stimuli, but not in skin from patients with basal or squamous cell carcinoma. Expression of a constitutively active form of RAC1 (RACV12) in mice resulted in the development of lesions similar to those of human psoriasis that required the presence of an intact immune system. RAC1V12-expressing mice and human psoriatic skin showed similar RAC1-dependent signaling as well as transcriptional overlap of differentially expressed epidermal and immune pathways. Coculture of PHKCs with immunocytes resulted in the upregulation of RAC1-dependent proinflammatory cytokines, an effect that was reproduced by overexpressing RAC1 in normal human keratinocytes. In keratinocytes, modulating RAC1 activity altered differentiation, proliferation, and inflammatory pathways, including STAT3, NFκB, and zinc finger protein 750 (ZNF750). Finally, RAC1 inhibition in xenografts composed of human PHKCs and immunocytes abolished psoriasiform hyperplasia and inflammation in vivo. These studies implicate RAC1 as a potential therapeutic target for psoriasis and as a key orchestrator of pathologic epidermis-immune interactions. PMID:27294528

  13. The Mitochondria-Regulated Immune Pathway Activated in the C. elegans Intestine Is Neuroprotective.

    PubMed

    Chikka, Madhusudana Rao; Anbalagan, Charumathi; Dvorak, Katherine; Dombeck, Kyle; Prahlad, Veena

    2016-08-30

    Immunological mediators that originate outside the nervous system can affect neuronal health. However, their roles in neurodegeneration remain largely unknown. Here, we show that the p38MAPK-mediated immune pathway activated in intestinal cells of Caenorhabditis elegans upon mitochondrial dysfunction protects neurons in a cell-non-autonomous fashion. Specifically, mitochondrial complex I dysfunction induced by rotenone activates the p38MAPK/CREB/ATF-7-dependent innate immune response pathway in intestinal cells of C. elegans. Activation of p38MAPK in the gut is neuroprotective. Enhancing the p38MAPK-mediated immune pathway in intestinal cells alone suppresses rotenone-induced dopaminergic neuron loss, while downregulating it in the intestine exacerbates neurodegeneration. The p38MAPK/ATF-7 immune pathway modulates autophagy and requires autophagy and the PTEN-induced putative kinase PINK-1 for conferring neuroprotection. Thus, mitochondrial damage induces the clearance of mitochondria by the immune pathway, protecting the organism from the toxic effects of mitochondrial dysfunction. We propose that mitochondria are subject to constant surveillance by innate immune mechanisms. PMID:27545884

  14. Arabidopsis resistance protein SNC1 activates immune responses through association with a transcriptional corepressor

    PubMed Central

    Zhu, Zhaohai; Xu, Fang; Zhang, Yaxi; Cheng, Yu Ti; Wiermer, Marcel; Li, Xin; Zhang, Yuelin

    2010-01-01

    In both plants and animals, nucleotide-binding (NB) domain and leucine-rich repeat (LRR)-containing proteins (NLR) function as sensors of pathogen-derived molecules and trigger immune responses. Although NLR resistance (R) proteins were first reported as plant immune receptors more than 15 years ago, how these proteins activate downstream defense responses is still unclear. Here we report that the Toll-like/interleukin-1 receptor (TIR)-NB-LRR R protein, suppressor of npr1-1, constitutive 1 (SNC1) functions through its associated protein, Topless-related 1 (TPR1). Knocking out TPR1 and its close homologs compromises immunity mediated by SNC1 and several other TIR-NB-LRR–type R proteins, whereas overexpression of TPR1 constitutively activates SNC1-mediated immune responses. TPR1 functions as a transcriptional corepressor and associates with histone deacetylase 19 in vivo. Among the target genes of TPR1 are Defense no Death 1 (DND1) and Defense no Death 2 (DND2), two known negative regulators of immunity that are repressed during pathogen infection, suggesting that TPR1 activates R protein-mediated immune responses through repression of negative regulators. PMID:20647385

  15. Luman/CREB3 recruitment factor regulates glucocorticoid receptor activity and is essential for prolactin-mediated maternal instinct.

    PubMed

    Martyn, Amanda C; Choleris, Elena; Gillis, Daniel J; Armstrong, John N; Amor, Talya R; McCluggage, Adam R R; Turner, Patricia V; Liang, Genqing; Cai, Kimberly; Lu, Ray

    2012-12-01

    The hypothalamic-pituitary-adrenal (HPA) axis is a major part of the neuroendocrine system in animal responses to stress. It is known that the HPA axis is attenuated at parturition to prevent detrimental effects of glucocorticoid secretion including inhibition of lactation and maternal responsiveness. Luman/CREB3 recruitment factor (LRF) was identified as a negative regulator of CREB3 which is involved in the endoplasmic reticulum stress response. Here, we report a LRF gene knockout mouse line that has a severe maternal behavioral defect. LRF(-/-) females lacked the instinct to tend pups; 80% of their litters died within 24 h, while most pups survived if cross-fostered. Prolactin levels were significantly repressed in lactating LRF(-/-) dams, with glucocorticoid receptor (GR) signaling markedly augmented. In cell culture, LRF repressed transcriptional activity of GR and promoted its protein degradation. LRF was found to colocalize with the known GR repressor, RIP140/NRIP1, which inhibits the activity by GR within specific nuclear punctates that are similar to LRF nuclear bodies. Furthermore, administration of prolactin or the GR antagonist RU486 restored maternal responses in mutant females. We thus postulate that LRF plays a critical role in the attenuation of the HPA axis through repression of glucocorticoid stress signaling during parturition and the postpartum period.

  16. Luman/CREB3 Recruitment Factor Regulates Glucocorticoid Receptor Activity and Is Essential for Prolactin-Mediated Maternal Instinct

    PubMed Central

    Martyn, Amanda C.; Choleris, Elena; Gillis, Daniel J.; Armstrong, John N.; Amor, Talya R.; McCluggage, Adam R. R.; Turner, Patricia V.; Liang, Genqing; Cai, Kimberly

    2012-01-01

    The hypothalamic-pituitary-adrenal (HPA) axis is a major part of the neuroendocrine system in animal responses to stress. It is known that the HPA axis is attenuated at parturition to prevent detrimental effects of glucocorticoid secretion including inhibition of lactation and maternal responsiveness. Luman/CREB3 recruitment factor (LRF) was identified as a negative regulator of CREB3 which is involved in the endoplasmic reticulum stress response. Here, we report a LRF gene knockout mouse line that has a severe maternal behavioral defect. LRF−/− females lacked the instinct to tend pups; 80% of their litters died within 24 h, while most pups survived if cross-fostered. Prolactin levels were significantly repressed in lactating LRF−/− dams, with glucocorticoid receptor (GR) signaling markedly augmented. In cell culture, LRF repressed transcriptional activity of GR and promoted its protein degradation. LRF was found to colocalize with the known GR repressor, RIP140/NRIP1, which inhibits the activity by GR within specific nuclear punctates that are similar to LRF nuclear bodies. Furthermore, administration of prolactin or the GR antagonist RU486 restored maternal responses in mutant females. We thus postulate that LRF plays a critical role in the attenuation of the HPA axis through repression of glucocorticoid stress signaling during parturition and the postpartum period. PMID:23071095

  17. Subversion of innate and adaptive immune activation induced by structurally modified lipopolysaccharide from Salmonella typhimurium.

    PubMed

    Pastelin-Palacios, Rodolfo; Gil-Cruz, Cristina; Pérez-Shibayama, Christian I; Moreno-Eutimio, Mario A; Cervantes-Barragán, Luisa; Arriaga-Pizano, Lourdes; Ludewig, Burkhard; Cunningham, Adam F; García-Zepeda, Eduardo A; Becker, Ingeborg; Alpuche-Aranda, Celia; Bonifaz, Laura; Gunn, John S; Isibasi, Armando; López-Macías, Constantino

    2011-08-01

    Salmonella are successful pathogens that infect millions of people every year. During infection, Salmonella typhimurium changes the structure of its lipopolysaccharide (LPS) in response to the host environment, rendering bacteria resistant to cationic peptide lysis in vitro. However, the role of these structural changes in LPS as in vivo virulence factors and their effects on immune responses and the generation of immunity are largely unknown. We report that modified LPS are less efficient than wild-type LPS at inducing pro-inflammatory responses. The impact of this LPS-mediated subversion of innate immune responses was demonstrated by increased mortality in mice infected with a non-lethal dose of an attenuated S. typhimurium strain mixed with the modified LPS moieties. Up-regulation of co-stimulatory molecules on antigen-presenting cells and CD4(+) T-cell activation were affected by these modified LPS. Strains of S. typhimurium carrying structurally modified LPS are markedly less efficient at inducing specific antibody responses. Immunization with modified LPS moiety preparations combined with experimental antigens, induced an impaired Toll-like receptor 4-mediated adjuvant effect. Strains of S. typhimurium carrying structurally modified LPS are markedly less efficient at inducing immunity against challenge with virulent S. typhimurium. Hence, changes in S. typhimurium LPS structure impact not only on innate immune responses but also on both humoral and cellular adaptive immune responses.

  18. Subversion of innate and adaptive immune activation induced by structurally modified lipopolysaccharide from Salmonella typhimurium

    PubMed Central

    Pastelin-Palacios, Rodolfo; Gil-Cruz, Cristina; Pérez-Shibayama, Christian I; Moreno-Eutimio, Mario A; Cervantes-Barragán, Luisa; Arriaga-Pizano, Lourdes; Ludewig, Burkhard; Cunningham, Adam F; García-Zepeda, Eduardo A; Becker, Ingeborg; Alpuche-Aranda, Celia; Bonifaz, Laura; Gunn, John S; Isibasi, Armando; López-Macías, Constantino

    2011-01-01

    Salmonella are successful pathogens that infect millions of people every year. During infection, Salmonella typhimurium changes the structure of its lipopolysaccharide (LPS) in response to the host environment, rendering bacteria resistant to cationic peptide lysis in vitro. However, the role of these structural changes in LPS as in vivo virulence factors and their effects on immune responses and the generation of immunity are largely unknown. We report that modified LPS are less efficient than wild-type LPS at inducing pro-inflammatory responses. The impact of this LPS-mediated subversion of innate immune responses was demonstrated by increased mortality in mice infected with a non-lethal dose of an attenuated S. typhimurium strain mixed with the modified LPS moieties. Up-regulation of co-stimulatory molecules on antigen-presenting cells and CD4+ T-cell activation were affected by these modified LPS. Strains of S. typhimurium carrying structurally modified LPS are markedly less efficient at inducing specific antibody responses. Immunization with modified LPS moiety preparations combined with experimental antigens, induced an impaired Toll-like receptor 4-mediated adjuvant effect. Strains of S. typhimurium carrying structurally modified LPS are markedly less efficient at inducing immunity against challenge with virulent S. typhimurium. Hence, changes in S. typhimurium LPS structure impact not only on innate immune responses but also on both humoral and cellular adaptive immune responses. PMID:21631497

  19. Antiviral Protection via RdRP-Mediated Stable Activation of Innate Immunity.

    PubMed

    Painter, Meghan M; Morrison, James H; Zoecklein, Laurie J; Rinkoski, Tommy A; Watzlawik, Jens O; Papke, Louisa M; Warrington, Arthur E; Bieber, Allan J; Matchett, William E; Turkowski, Kari L; Poeschla, Eric M; Rodriguez, Moses

    2015-12-01

    For many emerging and re-emerging infectious diseases, definitive solutions via sterilizing adaptive immunity may require years or decades to develop, if they are even possible. The innate immune system offers alternative mechanisms that do not require antigen-specific recognition or a priori knowledge of the causative agent. However, it is unclear whether effective stable innate immune system activation can be achieved without triggering harmful autoimmunity or other chronic inflammatory sequelae. Here, we show that transgenic expression of a picornavirus RNA-dependent RNA polymerase (RdRP), in the absence of other viral proteins, can profoundly reconfigure mammalian innate antiviral immunity by exposing the normally membrane-sequestered RdRP activity to sustained innate immune detection. RdRP-transgenic mice have life-long, quantitatively dramatic upregulation of 80 interferon-stimulated genes (ISGs) and show profound resistance to normally lethal viral challenge. Multiple crosses with defined knockout mice (Rag1, Mda5, Mavs, Ifnar1, Ifngr1, and Tlr3) established that the mechanism operates via MDA5 and MAVS and is fully independent of the adaptive immune system. Human cell models recapitulated the key features with striking fidelity, with the RdRP inducing an analogous ISG network and a strict block to HIV-1 infection. This RdRP-mediated antiviral mechanism does not depend on secondary structure within the RdRP mRNA but operates at the protein level and requires RdRP catalysis. Importantly, despite lifelong massive ISG elevations, RdRP mice are entirely healthy, with normal longevity. Our data reveal that a powerfully augmented MDA5-mediated activation state can be a well-tolerated mammalian innate immune system configuration. These results provide a foundation for augmenting innate immunity to achieve broad-spectrum antiviral protection. PMID:26633895

  20. Antiviral Protection via RdRP-Mediated Stable Activation of Innate Immunity.

    PubMed

    Painter, Meghan M; Morrison, James H; Zoecklein, Laurie J; Rinkoski, Tommy A; Watzlawik, Jens O; Papke, Louisa M; Warrington, Arthur E; Bieber, Allan J; Matchett, William E; Turkowski, Kari L; Poeschla, Eric M; Rodriguez, Moses

    2015-12-01

    For many emerging and re-emerging infectious diseases, definitive solutions via sterilizing adaptive immunity may require years or decades to develop, if they are even possible. The innate immune system offers alternative mechanisms that do not require antigen-specific recognition or a priori knowledge of the causative agent. However, it is unclear whether effective stable innate immune system activation can be achieved without triggering harmful autoimmunity or other chronic inflammatory sequelae. Here, we show that transgenic expression of a picornavirus RNA-dependent RNA polymerase (RdRP), in the absence of other viral proteins, can profoundly reconfigure mammalian innate antiviral immunity by exposing the normally membrane-sequestered RdRP activity to sustained innate immune detection. RdRP-transgenic mice have life-long, quantitatively dramatic upregulation of 80 interferon-stimulated genes (ISGs) and show profound resistance to normally lethal viral challenge. Multiple crosses with defined knockout mice (Rag1, Mda5, Mavs, Ifnar1, Ifngr1, and Tlr3) established that the mechanism operates via MDA5 and MAVS and is fully independent of the adaptive immune system. Human cell models recapitulated the key features with striking fidelity, with the RdRP inducing an analogous ISG network and a strict block to HIV-1 infection. This RdRP-mediated antiviral mechanism does not depend on secondary structure within the RdRP mRNA but operates at the protein level and requires RdRP catalysis. Importantly, despite lifelong massive ISG elevations, RdRP mice are entirely healthy, with normal longevity. Our data reveal that a powerfully augmented MDA5-mediated activation state can be a well-tolerated mammalian innate immune system configuration. These results provide a foundation for augmenting innate immunity to achieve broad-spectrum antiviral protection.

  1. Antiviral Protection via RdRP-Mediated Stable Activation of Innate Immunity

    PubMed Central

    Painter, Meghan M.; Morrison, James H.; Zoecklein, Laurie J.; Rinkoski, Tommy A.; Watzlawik, Jens O.; Papke, Louisa M.; Warrington, Arthur E.; Bieber, Allan J.; Matchett, William E.; Turkowski, Kari L.; Poeschla, Eric M.; Rodriguez, Moses

    2015-01-01

    For many emerging and re-emerging infectious diseases, definitive solutions via sterilizing adaptive immunity may require years or decades to develop, if they are even possible. The innate immune system offers alternative mechanisms that do not require antigen-specific recognition or a priori knowledge of the causative agent. However, it is unclear whether effective stable innate immune system activation can be achieved without triggering harmful autoimmunity or other chronic inflammatory sequelae. Here, we show that transgenic expression of a picornavirus RNA-dependent RNA polymerase (RdRP), in the absence of other viral proteins, can profoundly reconfigure mammalian innate antiviral immunity by exposing the normally membrane-sequestered RdRP activity to sustained innate immune detection. RdRP-transgenic mice have life-long, quantitatively dramatic upregulation of 80 interferon-stimulated genes (ISGs) and show profound resistance to normally lethal viral challenge. Multiple crosses with defined knockout mice (Rag1, Mda5, Mavs, Ifnar1, Ifngr1, and Tlr3) established that the mechanism operates via MDA5 and MAVS and is fully independent of the adaptive immune system. Human cell models recapitulated the key features with striking fidelity, with the RdRP inducing an analogous ISG network and a strict block to HIV-1 infection. This RdRP-mediated antiviral mechanism does not depend on secondary structure within the RdRP mRNA but operates at the protein level and requires RdRP catalysis. Importantly, despite lifelong massive ISG elevations, RdRP mice are entirely healthy, with normal longevity. Our data reveal that a powerfully augmented MDA5-mediated activation state can be a well-tolerated mammalian innate immune system configuration. These results provide a foundation for augmenting innate immunity to achieve broad-spectrum antiviral protection. PMID:26633895

  2. Danger signals activating innate immunity in graft-versus-host disease.

    PubMed

    Zeiser, Robert; Penack, Olaf; Holler, Ernst; Idzko, Marco

    2011-09-01

    Extensive cell death with consecutive release of danger signals can cause immune-mediated tissue destruction. The abundance of cell death is likely to determine the relevance of the danger signals as physiological mechanisms that counteract immune activation may be overruled. Such constellation is conceivable in chemo-/radiotherapy-induced tissue damage, reperfusion injury, trauma, and severe infection. Studies on graft-versus-host disease (GvHD) development have to consider the effects of chemo-/radiotherapy-related tissue damage leading to the release of exogenous and endogenous danger signals. Our previous work has demonstrated a role for adenosine-5'-triphosphate (ATP) as an endogenous danger signal in GvHD. Besides ATP, uric acid or soluble extracellular matrix components are functional danger signals that activate the NLRP3 inflammasome when released from dying cells or from extracellular matrix. In contrast to sterile inflammation, GvHD is more complex since bacterial components that leak through damaged intestinal barriers and the skin can activate pattern recognition receptors and directly contribute to GvHD pathogenesis. These exogenous danger signals transmit immune activation via toll-like receptors and NOD-like receptors of the innate immune system. This review covers both the impact of endogenous and exogenous danger signals activating innate immunity in GvHD.

  3. Endocrine Factors Modulating Immune Responses in Pregnancy

    PubMed Central

    Schumacher, Anne; Costa, Serban-Dan; Zenclussen, Ana Claudia

    2014-01-01

    How the semi-allogeneic fetus is tolerated by the maternal immune system remains a fascinating phenomenon. Despite extensive research activity in this field, the mechanisms underlying fetal tolerance are still not well understood. However, there are growing evidences that immune–immune interactions as well as immune–endocrine interactions build up a complex network of immune regulation that ensures fetal survival within the maternal uterus. In the present review, we aim to summarize emerging research data from our and other laboratories on immune modulating properties of pregnancy hormones with a special focus on progesterone, estradiol, and human chorionic gonadotropin. These pregnancy hormones are critically involved in the successful establishment, maintenance, and termination of pregnancy. They suppress detrimental maternal alloresponses while promoting tolerance pathways. This includes the reduction of the antigen-presenting capacity of dendritic cells (DCs), monocytes, and macrophages as well as the blockage of natural killer cells, T and B cells. Pregnancy hormones also support the proliferation of pregnancy supporting uterine killer cells, retain tolerogenic DCs, and efficiently induce regulatory T (Treg) cells. Furthermore, they are involved in the recruitment of mast cells and Treg cells into the fetal–maternal interface contributing to a local accumulation of pregnancy-protective cells. These findings highlight the importance of endocrine factors for the tolerance induction during pregnancy and encourage further research in the field. PMID:24847324

  4. Attenuation of Cocaine-Induced Locomotor Activity in Male and Female Mice by Active Immunization

    PubMed Central

    Kosten, Therese A.; Shen, Xiaoyun Y.; Kinsey, Berma M.; Kosten, Thomas R.; Orson, Frank M.

    2014-01-01

    Background and objectives Immunotherapy for drug addiction is being investigated in several laboratories but most studies are conducted in animals of one sex. Yet, women show heightened immune responses and are more likely to develop autoimmune diseases than men. The purpose of this study was to compare the effects of an active anti-cocaine vaccine, succinyl-norcocaine conjugated to keyhole limpet hemocyanin, for its ability to elicit antibodies and alter cocaine-induced ambulatory activity in male versus female mice. Methods Male and female BALB/c mice were vaccinated (n=44) or served as non-vaccinated controls (n=34). Three weeks after initial vaccination, a booster was given. Ambulatory activity induced by cocaine (20 mg/kg) was assessed at 7-wk and plasma obtained at 8-wk to assess antibody levels. Results High antibody titers were produced in mice of both sexes. The vaccine reduced ambulatory activity cocaine-induced but this effect was greater in female compared to male mice. Discussion and conclusions The efficacy of this anti-cocaine vaccine is demonstrated in mice of both sexes but its functional consequences are greater in females than males. Scientific significance Results point to the importance of testing animals of both sexes in studies of immunotherapies for addiction. PMID:25251469

  5. Maternal behavior.

    PubMed

    Crowell-Davis, S L; Houpt, K A

    1986-12-01

    Parturition in mares is rapid and is followed by a brief period of sensitivity to imprinting on a foal. There is large individual variation in normal maternal style, but normal mothers actively defend their foal, remain near the foal when it is sleeping, tolerate or assist nursing, and do not injure their own foal. Disturbance of a mare and foal during the early imprinting period can predispose a mare to rejection of her foal; therefore, it should be avoided. There are a variety of forms of foal rejection and numerous etiologies. Therefore, each case should be evaluated individually. PMID:3492245

  6. Cure of Trypanosoma musculi infection by heat-labile activity in immune plasma.

    PubMed

    Wechsler, D S; Kongshavn, P A

    1984-06-01

    Passive transfer of plasma from a mouse cured of parasitemia to a Trypanosoma musculi-infected host rapidly eliminates parasitemia; this curative activity, presumably mediated by an immunoglobulin, is sensitive to heat treatment (56 degrees C, 30 min). In addition, pretreatment with immune plasma, even after heat treatment, prevents the development of a patent parasitemia in a naive host (protective activity).

  7. Maternal and Child Health Bureau Active Projects FY 1991: An Annotated Listing.

    ERIC Educational Resources Information Center

    National Center for Education in Maternal and Child Health, Washington, DC.

    This annotated listing provides brief descriptions of the 591 projects funded during 1991 by federal set-aside funds of the Maternal and Child Health (MCH) Services Block Grant and identified as special projects of regional and national significance (SPRANS). Preliminary information includes an introduction, an organization chart of the Maternal…

  8. Learning Innovative Maternal Instinct: Activity Designing Semantic Factors of Alcohol Modification in Rural Communities of Thailand

    ERIC Educational Resources Information Center

    Yodmongkol, Pitipong; Jaimung, Thunyaporn; Chakpitak, Nopasit; Sureephong, Pradorn

    2014-01-01

    At present, Thailand is confronting a serious problem of alcohol drinking behavior which needs to be solved urgently. This research aimed to identify the semantic factors on alcohol drinking behavior and to use maternal instinct driving for housewives as village health volunteers in rural communities, Thailand. Two methods were implemented as the…

  9. Maternal diet-induced obesity alters mitochondrial activity and redox status in mouse oocytes and zygotes.

    PubMed

    Igosheva, Natalia; Abramov, Andrey Y; Poston, Lucilla; Eckert, Judith J; Fleming, Tom P; Duchen, Michael R; McConnell, Josie

    2010-01-01

    The negative impact of obesity on reproductive success is well documented but the stages at which development of the conceptus is compromised and the mechanisms responsible for the developmental failure still remain unclear. Recent findings suggest that mitochondria may be a contributing factor. However to date no studies have directly addressed the consequences of maternal obesity on mitochondria in early embryogenesis.Using an established murine model of maternal diet induced obesity and a live cell dynamic fluorescence imaging techniques coupled with molecular biology we have investigated the underlying mechanisms of obesity-induced reduced fertility. Our study is the first to show that maternal obesity prior to conception is associated with altered mitochondria in mouse oocytes and zygotes. Specifically, maternal diet-induced obesity in mice led to an increase in mitochondrial potential, mitochondrial DNA content and biogenesis. Generation of reactive oxygen species (ROS) was raised while glutathione was depleted and the redox state became more oxidised, suggestive of oxidative stress. These altered mitochondrial properties were associated with significant developmental impairment as shown by the increased number of obese mothers who failed to support blastocyst formation compared to lean dams. We propose that compromised oocyte and early embryo mitochondrial metabolism, resulting from excessive nutrient exposure prior to and during conception, may underlie poor reproductive outcomes frequently reported in obese women.

  10. Maternal soothing and infant stress responses: soothing, crying and adrenocortical activity during inoculation.

    PubMed

    Braarud, Hanne Cecilie; Stormark, Kjell Morten

    2006-01-01

    The relation between maternal soothing and infant stress response during inoculation was examined in a sample of 37 mothers and their 3-month-old infants. The mothers' soothing and the infants' cry vocalizations and the mothers' and the infants' salivary cortisol level pre- and post-injection were analysed. There was a positive relation between infants' cry vocalization post-injection and maternal soothing pre- and post-injection. The sample was divided in two sub-groups depending on whether the mothers evidenced most soothing of the infants in the period before (Preparatory group; n=20) or after (Contingent group; n=17) the syringe injection. In the Preparatory group, the duration of infant cry vocalizations was related to amount of maternal soothing before and after the injection, while cry vocalizations in the Contingent group was related to amount of maternal soothing after the injection. The Contingent infants responded to the injection with a significant increase in cortisol, while there was no increase in the Preparatory infants. The Preparatory infants evidenced significantly longer duration of looking at the target stimuli in a visual marking task, suggesting greater difficulties in disengaging attention. These findings indicate that 3-month-olds' stress responses and their mothers' situational behaviour are mutually regulated.

  11. Maternal overweight induces integrative changes in gene expression in the offspring in metabolically active tissues

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gestational exposure to maternal overweight (OW) influences the risk of obesity in adult-life. Male offspring from OW rat dams (Sprague Dawley) gain greater body weight (p less than 0.005), fat mass and develop insulin resistance when fed high-fat diets (45 percent fat). Hepatic microarray analyses ...

  12. A Strategy for the Evaluation of Activities to Reduce Maternal Mortality in Developing Countries.

    ERIC Educational Resources Information Center

    Ward, Victoria M.; And Others

    1994-01-01

    An evaluation strategy in which a set of process indicators is applied to programs to reduce maternal mortality in developing countries is presented. The four-stage strategy is illustrated for three interventions: (1) providing safe abortion services; (2) increasing knowledge of obstetric complications; and (3) improving medical care quality. (SLD)

  13. Phenoloxidase activity in the infraorder Isoptera: unraveling life-history correlates of immune investment.

    PubMed

    Rosengaus, Rebeca B; Reichheld, Jennifer L

    2016-02-01

    Within the area of ecological immunology, the quantification of phenoloxidase (PO) activity has been used as a proxy for estimating immune investment. Because termites have unique life-history traits and significant inter-specific differences exist regarding their nesting and foraging habits, comparative studies on PO activity can shed light on the general principles influencing immune investment against the backdrop of sociality, reproductive potential, and gender. We quantified PO activity across four termite species ranging from the phylogenetically basal to the most derived, each with their particular nesting/foraging strategies. Our data indicate that PO activity varies across species, with soil-dwelling termites exhibiting significantly higher PO levels than the above-ground wood nester species which in turn have higher PO levels than arboreal species. Moreover, our comparative approach suggests that pathogenic risks can override reproductive potential as a more important driver of immune investment. No gender-based differences in PO activities were recorded. Although termite PO activity levels vary in accordance with a priori predictions made from life-history theory, our data indicate that nesting and foraging strategies (and their resulting pathogenic pressures) can supersede reproductive potential and other life-history traits in influencing investment in PO. Termites, within the eusocial insects, provide a unique perspective for inferring how different ecological pressures may have influenced immune function in general and their levels of PO activity, in particular.

  14. Phenoloxidase activity in the infraorder Isoptera: unraveling life-history correlates of immune investment

    NASA Astrophysics Data System (ADS)

    Rosengaus, Rebeca B.; Reichheld, Jennifer L.

    2016-02-01

    Within the area of ecological immunology, the quantification of phenoloxidase (PO) activity has been used as a proxy for estimating immune investment. Because termites have unique life-history traits and significant inter-specific differences exist regarding their nesting and foraging habits, comparative studies on PO activity can shed light on the general principles influencing immune investment against the backdrop of sociality, reproductive potential, and gender. We quantified PO activity across four termite species ranging from the phylogenetically basal to the most derived, each with their particular nesting/foraging strategies. Our data indicate that PO activity varies across species, with soil-dwelling termites exhibiting significantly higher PO levels than the above-ground wood nester species which in turn have higher PO levels than arboreal species. Moreover, our comparative approach suggests that pathogenic risks can override reproductive potential as a more important driver of immune investment. No gender-based differences in PO activities were recorded. Although termite PO activity levels vary in accordance with a priori predictions made from life-history theory, our data indicate that nesting and foraging strategies (and their resulting pathogenic pressures) can supersede reproductive potential and other life-history traits in influencing investment in PO. Termites, within the eusocial insects, provide a unique perspective for inferring how different ecological pressures may have influenced immune function in general and their levels of PO activity, in particular.

  15. Phenoloxidase activity in the infraorder Isoptera: unraveling life-history correlates of immune investment.

    PubMed

    Rosengaus, Rebeca B; Reichheld, Jennifer L

    2016-02-01

    Within the area of ecological immunology, the quantification of phenoloxidase (PO) activity has been used as a proxy for estimating immune investment. Because termites have unique life-history traits and significant inter-specific differences exist regarding their nesting and foraging habits, comparative studies on PO activity can shed light on the general principles influencing immune investment against the backdrop of sociality, reproductive potential, and gender. We quantified PO activity across four termite species ranging from the phylogenetically basal to the most derived, each with their particular nesting/foraging strategies. Our data indicate that PO activity varies across species, with soil-dwelling termites exhibiting significantly higher PO levels than the above-ground wood nester species which in turn have higher PO levels than arboreal species. Moreover, our comparative approach suggests that pathogenic risks can override reproductive potential as a more important driver of immune investment. No gender-based differences in PO activities were recorded. Although termite PO activity levels vary in accordance with a priori predictions made from life-history theory, our data indicate that nesting and foraging strategies (and their resulting pathogenic pressures) can supersede reproductive potential and other life-history traits in influencing investment in PO. Termites, within the eusocial insects, provide a unique perspective for inferring how different ecological pressures may have influenced immune function in general and their levels of PO activity, in particular. PMID:26838762

  16. IgE epitope proximity determines immune complex shape and effector cell activation capacity

    PubMed Central

    Gieras, Anna; Linhart, Birgit; Roux, Kenneth H.; Dutta, Moumita; Khodoun, Marat; Zafred, Domen; Cabauatan, Clarissa R.; Lupinek, Christian; Weber, Milena; Focke-Tejkl, Margarete; Keller, Walter; Finkelman, Fred D.; Valenta, Rudolf

    2016-01-01

    Background IgE-allergen complexes induce mast cell and basophil activation and thus immediate allergic inflammation. They are also important for IgE-facilitated allergen presentation to T cells by antigen-presenting cells. Objective To investigate whether the proximity of IgE binding sites on an allergen affects immune complex shape and subsequent effector cell activation in vitro and in vivo. Methods We constructed artificial allergens by grafting IgE epitopes in different numbers and proximity onto a scaffold protein. The shape of immune complexes formed between artificial allergens and the corresponding IgE was studied by negative-stain electron microscopy. Allergenic activity was determined using basophil activation assays. Mice were primed with IgE, followed by injection of artificial allergens to evaluate their in vivo allergenic activity. Severity of systemic anaphylaxis was measured by changes in body temperature. Results We could demonstrate simultaneous binding of 4 IgE antibodies in close vicinity to each other. The proximity of IgE binding sites on allergens influenced the shape of the resulting immune complexes and the magnitude of effector cell activation and in vivo inflammation. Conclusions Our results demonstrate that the proximity of IgE epitopes on an allergen affects its allergenic activity. We thus identified a novel mechanism by which IgE-allergen complexes regulate allergic inflammation. This mechanism should be important for allergy and other immune complex–mediated diseases. PMID:26684291

  17. A Novel Polysaccharide in Insects Activates the Innate Immune System in Mouse Macrophage RAW264 Cells

    PubMed Central

    Ohta, Takashi; Ido, Atsushi; Kusano, Kie; Miura, Chiemi; Miura, Takeshi

    2014-01-01

    A novel water-soluble polysaccharide was identified in the pupae of the melon fly (Bactrocera cucurbitae) as a molecule that activates the mammalian innate immune response. We attempted to purify this innate immune activator using nitric oxide (NO) production in mouse RAW264 macrophages as an indicator of immunostimulatory activity. A novel acidic polysaccharide was identified, which we named “dipterose”, with a molecular weight of 1.01×106 and comprising nine monosaccharides. Dipterose was synthesized in the melon fly itself at the pupal stage. The NO-producing activity of dipterose was approximately equal to that of lipopolysaccharide, a potent immunostimulator. Inhibition of Toll-like receptor 4 (TLR4) led to the suppression of NO production by dipterose. Furthermore, dipterose induced the expression of proinflammatory cytokines and interferon β (IFNβ) and promoted the activation of nuclear factor kappa B (NF-κB) in macrophages, indicating that it stimulates the induction of various cytokines in RAW264 cells via the TLR4 signaling pathway. Our results thus suggest that dipterose activates the innate immune response against various pathogenic microorganisms and viral infections. This is the first identification of an innate immune-activating polysaccharide from an animal. PMID:25490773

  18. CRF-R1 activation in the anterior-dorsal BNST induces maternal neglect in lactating rats via an HPA axis-independent central mechanism

    PubMed Central

    Klampfl, Stefanie M.; Brunton, Paula J.; Bayerl, Doris S.; Bosch, Oliver J.

    2016-01-01

    Adequate maternal behavior in rats requires minimal corticotropin-releasing factor receptor (CRF-R) activation in the medial-posterior bed nucleus of the stria terminalis (mpBNST). Based on the architectural heterogeneity of the BNST and its distinct inter-neural connectivity, we tested whether CRF-R manipulation in another functional part, the anterior-dorsal BNST (adBNST), differentially modulates maternal behavior. We demonstrate that in the adBNST, activation of CRF-R1 reduced arched back nursing (ABN) and nursing, whereas activation of CRF-R2 resulted in an initial reduction in nursing but significantly increased the incidence of ABN 5 h after the treatment. Following stressor exposure, which is detrimental to maternal care, ABN tended to be protected by CRF-R1 blockade. Maternal motivation, maternal aggression, and anxiety were unaffected by any manipulation. Furthermore, under basal and stress conditions, activation of adBNST CRF-R1 increased plasma ACTH and corticosterone concentrations, whereas stimulation of adBNST CRF-R2 increased basal plasma ACTH and corticosterone concentrations, but blocked the stress-induced increase in plasma corticosterone secretion. Moreover, both the CRF-R1 and -R2 antagonists prevented the stress-induced increase in plasma corticosterone secretion. Importantly, elevated levels of circulating corticosterone induced by intra-adBNST administration of CRF-R1 or -R2 agonist did not impact maternal care. Finally, Crf mRNA expression in the adBNST was increased during lactation; however, Crfr1 mRNA expression was similar between lactating and virgin rats. In conclusion, maternal care is impaired by adBNST CRF-R1 activation, and this appears to be the result of a central action, rather than an effect of elevated circulating levels of CORT. These data provide new insights into potential causes of disturbed maternal behavior postpartum. PMID:26630389

  19. CRF-R1 activation in the anterior-dorsal BNST induces maternal neglect in lactating rats via an HPA axis-independent central mechanism.

    PubMed

    Klampfl, Stefanie M; Brunton, Paula J; Bayerl, Doris S; Bosch, Oliver J

    2016-02-01

    Adequate maternal behavior in rats requires minimal corticotropin-releasing factor receptor (CRF-R) activation in the medial-posterior bed nucleus of the stria terminalis (mpBNST). Based on the architectural heterogeneity of the BNST and its distinct inter-neural connectivity, we tested whether CRF-R manipulation in another functional part, the anterior-dorsal BNST (adBNST), differentially modulates maternal behavior. We demonstrate that in the adBNST, activation of CRF-R1 reduced arched back nursing (ABN) and nursing, whereas activation of CRF-R2 resulted in an initial reduction in nursing but significantly increased the incidence of ABN 5h after the treatment. Following stressor exposure, which is detrimental to maternal care, ABN tended to be protected by CRF-R1 blockade. Maternal motivation, maternal aggression, and anxiety were unaffected by any manipulation. Furthermore, under basal and stress conditions, activation of adBNST CRF-R1 increased plasma ACTH and corticosterone concentrations, whereas stimulation of adBNST CRF-R2 increased basal plasma ACTH and corticosterone concentrations, but blocked the stress-induced increase in plasma corticosterone secretion. Moreover, both the CRF-R1 and -R2 antagonists prevented the stress-induced increase in plasma corticosterone secretion. Importantly, elevated levels of circulating corticosterone induced by intra-adBNST administration of CRF-R1 or -R2 agonist did not impact maternal care. Finally, Crf mRNA expression in the adBNST was increased during lactation; however, Crfr1 mRNA expression was similar between lactating and virgin rats. In conclusion, maternal care is impaired by adBNST CRF-R1 activation, and this appears to be the result of a central action, rather than an effect of elevated circulating levels of CORT. These data provide new insights into potential causes of disturbed maternal behavior postpartum.

  20. Vitamin D3 alters microglia immune activation by an IL-10 dependent SOCS3 mechanism.

    PubMed

    Boontanrart, Mandy; Hall, Samuel D; Spanier, Justin A; Hayes, Colleen E; Olson, Julie K

    2016-03-15

    Microglia become activated immune cells during infection or disease in the central nervous system (CNS). However, the mechanisms that downregulate activated microglia to prevent immune-mediated damage are not completely understood. Vitamin D3 has been suggested to have immunomodulatory affects, and high levels of vitamin D3 have been correlated with a decreased risk for developing some neurological diseases. Recent studies have demonstrated the synthesis of active vitamin D3, 1,25-dihydroxyvitamin D3, within the CNS, but its cellular source and neuroprotective actions remain unknown. Therefore, we wanted to determine whether microglia can respond to vitamin D3 and whether vitamin D3 alters immune activation of microglia. We have previously shown that microglia become activated by IFNγ or LPS or by infection with virus to express pro-inflammatory cytokines, chemokines, and effector molecules. In this study, activated microglia increased the expression of the vitamin D receptor and Cyp27b1, which encodes the enzyme for converting vitamin D3 into its active form, thereby enhancing their responsiveness to vitamin D3. Most importantly, the activated microglia exposed to vitamin D3 had reduced expression of pro-inflammatory cytokines, IL-6, IL-12, and TNFα, and increased expression of IL-10. The reduction in pro-inflammatory cytokines was dependent on IL-10 induction of suppressor of cytokine signaling-3 (SOCS3). Therefore, vitamin D3 increases the expression of IL-10 creating a feedback loop via SOCS3 that downregulates the pro-inflammatory immune response by activated microglia which would likewise prevent immune mediated damage in the CNS. PMID:26943970

  1. Vitamin D3 alters microglia immune activation by an IL-10 dependent SOCS3 mechanism.

    PubMed

    Boontanrart, Mandy; Hall, Samuel D; Spanier, Justin A; Hayes, Colleen E; Olson, Julie K

    2016-03-15

    Microglia become activated immune cells during infection or disease in the central nervous system (CNS). However, the mechanisms that downregulate activated microglia to prevent immune-mediated damage are not completely understood. Vitamin D3 has been suggested to have immunomodulatory affects, and high levels of vitamin D3 have been correlated with a decreased risk for developing some neurological diseases. Recent studies have demonstrated the synthesis of active vitamin D3, 1,25-dihydroxyvitamin D3, within the CNS, but its cellular source and neuroprotective actions remain unknown. Therefore, we wanted to determine whether microglia can respond to vitamin D3 and whether vitamin D3 alters immune activation of microglia. We have previously shown that microglia become activated by IFNγ or LPS or by infection with virus to express pro-inflammatory cytokines, chemokines, and effector molecules. In this study, activated microglia increased the expression of the vitamin D receptor and Cyp27b1, which encodes the enzyme for converting vitamin D3 into its active form, thereby enhancing their responsiveness to vitamin D3. Most importantly, the activated microglia exposed to vitamin D3 had reduced expression of pro-inflammatory cytokines, IL-6, IL-12, and TNFα, and increased expression of IL-10. The reduction in pro-inflammatory cytokines was dependent on IL-10 induction of suppressor of cytokine signaling-3 (SOCS3). Therefore, vitamin D3 increases the expression of IL-10 creating a feedback loop via SOCS3 that downregulates the pro-inflammatory immune response by activated microglia which would likewise prevent immune mediated damage in the CNS.

  2. Immune activation promotes evolutionary conservation of T-cell epitopes in HIV-1.

    PubMed

    Sanjuán, Rafael; Nebot, Miguel R; Peris, Joan B; Alcamí, José

    2013-01-01

    The immune system should constitute a strong selective pressure promoting viral genetic diversity and evolution. However, HIV shows lower sequence variability at T-cell epitopes than elsewhere in the genome, in contrast with other human RNA viruses. Here, we propose that epitope conservation is a consequence of the particular interactions established between HIV and the immune system. On one hand, epitope recognition triggers an anti-HIV response mediated by cytotoxic T-lymphocytes (CTLs), but on the other hand, activation of CD4(+) helper T lymphocytes (TH cells) promotes HIV replication. Mathematical modeling of these opposite selective forces revealed that selection at the intrapatient level can promote either T-cell epitope conservation or escape. We predict greater conservation for epitopes contributing significantly to total immune activation levels (immunodominance), and when TH cell infection is concomitant to epitope recognition (trans-infection). We suggest that HIV-driven immune activation in the lymph nodes during the chronic stage of the disease may offer a favorable scenario for epitope conservation. Our results also support the view that some pathogens draw benefits from the immune response and suggest that vaccination strategies based on conserved TH epitopes may be counterproductive.

  3. Activation of antitumor immune responses by Ganoderma formosanum polysaccharides in tumor-bearing mice.

    PubMed

    Wang, Cheng-Li; Lu, Chiu-Ying; Hsueh, Ying-Chao; Liu, Wen-Hsiung; Chen, Chun-Jen

    2014-11-01

    Fungi of the genus Ganoderma are basidiomycetes that have been used as traditional medicine in Asia and have been shown to exhibit various pharmacological activities. We recently found that PS-F2, a polysaccharide fraction purified from the submerged culture broth of Ganoderma formosanum, stimulates the maturation of dendritic cells and primes a T helper 1 (Th1)-polarized adaptive immune response in vivo. In this study, we investigated whether the immune adjuvant function of PS-F2 can stimulate antitumor immune responses in tumor-bearing mice. Continuous intraperitoneal or oral administration of PS-F2 effectively suppressed the growth of colon 26 (C26) adenocarcinoma, B16 melanoma, and sarcoma 180 (S180) tumor cells in mice without adverse effects on the animals' health. PS-F2 did not cause direct cytotoxicity on tumor cells, and it lost the antitumor effect in mice with severe combined immunodeficiency (SCID). CD4(+) T cells, CD8(+) T cells, and serum from PS-F2-treated tumor-bearing mice all exhibited antitumor activities when adoptively transferred to naïve animals, indicating that PS-F2 treatment stimulates tumor-specific cellular and humoral immune responses. These data demonstrate that continuous administration of G. formosanum polysaccharide PS-F2 can activate host immune responses against ongoing tumor growth, suggesting that PS-F2 can potentially be developed into a preventive/therapeutic agent for cancer immunotherapy.

  4. Imaging Granzyme B Activity Assesses Immune-Mediated Myocarditis

    PubMed Central

    Weissleder, Ralph; Lichtman, Andrew H.; McCarthy, Jason R.; Libby, Peter

    2015-01-01

    Rationale The development of molecular imaging approaches that assess specific immunopathologic mechanisms can advance the study of myocarditides. Objective This study validates a novel molecular imaging tool that enables the in vivo visualization of granzyme B activity, a major effector of cytotoxic CD8+ T lymphocytes. Methods and Results We synthesized and optimized a fluorogenic substrate capable of reporting on granzyme B activity and examined its specificity ex vivo in mice hearts with experimental cytotoxic CD8+ T lymphocyte-mediated myocarditis using fluorescence reflectance imaging (FRI), validated by histologic examination. In vivo experiments localized granzyme B activity in hearts with acute myocarditis monitored by fluorescent molecular tomography in conjunction with co-registered computed tomography imaging (FMT-CT). A model anti-inflammatory intervention (dexamethasone administration) in vivo reduced granzyme B activity (vehicle vs. dexamethasone: 504±263 vs. 194±77 fluorescence intensities in hearts, P=0.002). Conclusions Molecular imaging of granzyme B activity can visualize T cell-mediated myocardial injury and monitor the response to an anti-inflammatory intervention. PMID:26199323

  5. Immune effects and antiacetylcholinesterase activity of Polygonum hydropiper L.

    PubMed

    Miyazaki, Yoshiko

    2016-01-01

    To determine the potential utility of Polygonum hydropiper (tade) as an anti-dementia functional food, the present study assessed the acetylcholinesterase inhibitory and anti-inflammatory activities of tade crude extracts in human cells. Crude extracts of tade were obtained by homogenizing tade in distilled water and then heating the resulting crude extracts. The hot aqueous extracts were purified by centrifugation and freeze-dried. The inhibition of acetylcholinesterase (AChE) by tade was investigated quantitatively by Ellman's method. Furthermore, the in vitro effects on human leukocytes (phagocytic activity, phagosome-lysosome fusion, and superoxide anion release) of coating inactive Staphylococcus aureus cells with tade crude extracts were studied. The tade crude extracts inhibited AChE activity. Furthermore, they increased phagocytic activity and phagosome-lysosome fusion in human neutrophils and monocytes in a nominally dose-dependent manner. However, the tade crude extracts did not alter superoxide anion release (O2 (-)) from neutrophils. Our results confirmed that crude extracts of P. hydropiper exhibit antiacetylcholinesterase and immunostimulation activities in vitro. P. hydropiper thus is a candidate functional food for the prevention of dementia. PMID:27200260

  6. Immune effects and antiacetylcholinesterase activity of Polygonum hydropiper L.

    PubMed Central

    MIYAZAKI, Yoshiko

    2015-01-01

    To determine the potential utility of Polygonum hydropiper (tade) as an anti-dementia functional food, the present study assessed the acetylcholinesterase inhibitory and anti-inflammatory activities of tade crude extracts in human cells. Crude extracts of tade were obtained by homogenizing tade in distilled water and then heating the resulting crude extracts. The hot aqueous extracts were purified by centrifugation and freeze-dried. The inhibition of acetylcholinesterase (AChE) by tade was investigated quantitatively by Ellman’s method. Furthermore, the in vitro effects on human leukocytes (phagocytic activity, phagosome-lysosome fusion, and superoxide anion release) of coating inactive Staphylococcus aureus cells with tade crude extracts were studied. The tade crude extracts inhibited AChE activity. Furthermore, they increased phagocytic activity and phagosome-lysosome fusion in human neutrophils and monocytes in a nominally dose-dependent manner. However, the tade crude extracts did not alter superoxide anion release (O2−) from neutrophils. Our results confirmed that crude extracts of P. hydropiper exhibit antiacetylcholinesterase and immunostimulation activities in vitro. P. hydropiper thus is a candidate functional food for the prevention of dementia. PMID:27200260

  7. Immune effects and antiacetylcholinesterase activity of Polygonum hydropiper L.

    PubMed

    Miyazaki, Yoshiko

    2016-01-01

    To determine the potential utility of Polygonum hydropiper (tade) as an anti-dementia functional food, the present study assessed the acetylcholinesterase inhibitory and anti-inflammatory activities of tade crude extracts in human cells. Crude extracts of tade were obtained by homogenizing tade in distilled water and then heating the resulting crude extracts. The hot aqueous extracts were purified by centrifugation and freeze-dried. The inhibition of acetylcholinesterase (AChE) by tade was investigated quantitatively by Ellman's method. Furthermore, the in vitro effects on human leukocytes (phagocytic activity, phagosome-lysosome fusion, and superoxide anion release) of coating inactive Staphylococcus aureus cells with tade crude extracts were studied. The tade crude extracts inhibited AChE activity. Furthermore, they increased phagocytic activity and phagosome-lysosome fusion in human neutrophils and monocytes in a nominally dose-dependent manner. However, the tade crude extracts did not alter superoxide anion release (O2 (-)) from neutrophils. Our results confirmed that crude extracts of P. hydropiper exhibit antiacetylcholinesterase and immunostimulation activities in vitro. P. hydropiper thus is a candidate functional food for the prevention of dementia.

  8. MALT1 Protease Activity Is Required for Innate and Adaptive Immune Responses

    PubMed Central

    Yu, Jong W.; Hoffman, Sandy; Beal, Allison M.; Dykon, Angela; Ringenberg, Michael A.; Hughes, Anna C.; Dare, Lauren; Anderson, Amber D.; Finger, Joshua; Kasparcova, Viera; Rickard, David; Berger, Scott B.; Ramanjulu, Joshi; Emery, John G.; Gough, Peter J.; Bertin, John; Foley, Kevin P.

    2015-01-01

    CARMA-BCL10-MALT1 signalosomes play important roles in antigen receptor signaling and other pathways. Previous studies have suggested that as part of this complex, MALT1 functions as both a scaffolding protein to activate NF-κB through recruitment of ubiquitin ligases, and as a protease to cleave and inactivate downstream inhibitory signaling proteins. However, our understanding of the relative importance of these two distinct MALT1 activities has been hampered by a lack of selective MALT1 protease inhibitors with suitable pharmacologic properties. To fully investigate the role of MALT1 protease activity, we generated mice homozygous for a protease-dead mutation in MALT1. We found that some, but not all, MALT1 functions in immune cells were dependent upon its protease activity. Protease-dead mice had defects in the generation of splenic marginal zone and peritoneal B1 B cells. CD4+ and CD8+ T cells displayed decreased T cell receptor-stimulated proliferation and IL-2 production while B cell receptor-stimulated proliferation was partially dependent on protease activity. In dendritic cells, stimulation of cytokine production through the Dectin-1, Dectin-2, and Mincle C-type lectin receptors was also found to be partially dependent upon protease activity. In vivo, protease-dead mice had reduced basal immunoglobulin levels, and showed defective responses to immunization with T-dependent and T-independent antigens. Surprisingly, despite these decreased responses, MALT1 protease-dead mice, but not MALT1 null mice, developed mixed inflammatory cell infiltrates in multiple organs, suggesting MALT1 protease activity plays a role in immune homeostasis. These findings highlight the importance of MALT1 protease activity in multiple immune cell types, and in integrating immune responses in vivo. PMID:25965667

  9. Pregnancy Associated with Systemic Lupus Erythematosus: Immune Tolerance in Pregnancy and Its Deficiency in Systemic Lupus Erythematosus—An Immunological Dilemma

    PubMed Central

    Velciov, Silvia; Gluhovschi, Adrian

    2015-01-01

    Pregnancy is a physiological condition that requires immune tolerance to the product of conception. Systemic lupus erythematosus (SLE) is a disease with well-represented immune mechanisms that disturb immune tolerance. The association of pregnancy with systemic lupus erythematosus creates a particular immune environment in which the immune tolerance specific of pregnancy is required to coexist with alterations of the immune system caused by SLE. The main role is played by T regulatory (Treg) cells, which attempt to regulate and adapt the immune system of the mother to the new conditions of pregnancy. Other components of the immune system also participate to maintain maternal-fetal immune tolerance. If the immune system of pregnant women with SLE is not able to maintain maternal immune tolerance to the fetus, pregnancy complications (miscarriage, fetal hypotrophy, and preterm birth) or maternal complications (preeclampsia or activation of SLE, especially in conditions of lupus nephritis) may occur. In certain situations this can be responsible for neonatal lupus. At the same time, it must be noted that during pregnancy, the immune system is able to achieve immune tolerance while maintaining the anti-infectious immune capacity of the mother. Immunological monitoring of pregnancy during SLE, as well as of the mother's disease, is required. It is important to understand immune tolerance to grafts in transplant pathology. PMID:26090485

  10. Effects of immunomodulators on functional activity of innate immunity cells infected with Streptococcus pneumoniae.

    PubMed

    Plekhova, N G; Kondrashova, N M; Somova, L M; Drobot, E I; Lyapun, I N

    2015-02-01

    Low activity of bactericidal enzymes was found in innate immunity cells infected with S. pneumonia. The death of these cells was fastened under these conditions. On the contrary, treatment with antibiotic maxifloxacin was followed by an increase in activity of bactericidal enzymes in phagocytes and induced their death via necrosis. Analysis of the therapeutic properties of immunomodulators tinrostim and licopid in combination with maxifloxacin showed that these combinations correct functional activity of cells infected with S. pneumonia. PMID:25708326

  11. Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression.

    PubMed

    Fairfax, Benjamin P; Humburg, Peter; Makino, Seiko; Naranbhai, Vivek; Wong, Daniel; Lau, Evelyn; Jostins, Luke; Plant, Katharine; Andrews, Robert; McGee, Chris; Knight, Julian C

    2014-03-01

    To systematically investigate the impact of immune stimulation upon regulatory variant activity, we exposed primary monocytes from 432 healthy Europeans to interferon-γ (IFN-γ) or differing durations of lipopolysaccharide and mapped expression quantitative trait loci (eQTLs). More than half of cis-eQTLs identified, involving hundreds of genes and associated pathways, are detected specifically in stimulated monocytes. Induced innate immune activity reveals multiple master regulatory trans-eQTLs including the major histocompatibility complex (MHC), coding variants altering enzyme and receptor function, an IFN-β cytokine network showing temporal specificity, and an interferon regulatory factor 2 (IRF2) transcription factor-modulated network. Induced eQTL are significantly enriched for genome-wide association study loci, identifying context-specific associations to putative causal genes including CARD9, ATM, and IRF8. Thus, applying pathophysiologically relevant immune stimuli assists resolution of functional genetic variants.

  12. Critical roles of co-activation receptor DNAX accessory molecule-1 in natural killer cell immunity

    PubMed Central

    Xiong, Peng; Sang, Hai-Wei; Zhu, Min

    2015-01-01

    Natural killer (NK) cells, which can exert early and powerful anti-tumour and anti-viral responses, are important components of the innate immune system. DNAX accessory molecule-1 (DNAM-1) is an activating receptor molecule expressed on the surface of NK cells. Recent findings suggest that DNAM-1 is a critical regulator of NK cell biology. DNAM-1 is involved in NK cell education and differentiation, and also plays a pivotal role in the development of cancer, viral infections and immune-related diseases. However, tumours and viruses have developed multiple mechanisms to evade the immune system. They are able to impair DNAM-1 activity by targeting the DNAM-1 receptor–ligand system. We have reviewed the roles of DNAM-1, and its biological functions, with respect to NK cell biology and DNAM-1 chimeric antigen receptor-based immunotherapy. PMID:26235210

  13. Innate Immune Activity Conditions the Effect of Regulatory Variants upon Monocyte Gene Expression

    PubMed Central

    Fairfax, Benjamin P.; Naranbhai, Vivek; Wong, Daniel; Lau, Evelyn; Jostins, Luke; Plant, Katharine; Andrews, Robert; McGee, Chris; Knight, Julian C.

    2014-01-01

    To systematically investigate the impact of immune stimulation upon regulatory variant activity, we exposed primary monocytes from 432 healthy Europeans to interferon-γ (IFN-γ) or differing durations of lipopolysaccharide and mapped expression quantitative trait loci (eQTLs). More than half of cis-eQTLs identified, involving hundreds of genes and associated pathways, are detected specifically in stimulated monocytes. Induced innate immune activity reveals multiple master regulatory trans-eQTLs including the major histocompatibility complex (MHC), coding variants altering enzyme and receptor function, an IFN-β cytokine network showing temporal specificity, and an interferon regulatory factor 2 (IRF2) transcription factor–modulated network. Induced eQTL are significantly enriched for genome-wide association study loci, identifying context-specific associations to putative causal genes including CARD9, ATM, and IRF8. Thus, applying pathophysiologically relevant immune stimuli assists resolution of functional genetic variants. PMID:24604202

  14. Quantitative Evaluation of Stomatal Cytoskeletal Patterns during the Activation of Immune Signaling in Arabidopsis thaliana

    PubMed Central

    Shimono, Masaki; Higaki, Takumi; Kaku, Hanae; Shibuya, Naoto; Hasezawa, Seiichiro

    2016-01-01

    Historically viewed as primarily functioning in the regulation of gas and water vapor exchange, it is now evident that stomata serve an important role in plant immunity. Indeed, in addition to classically defined functions related to cell architecture and movement, the actin cytoskeleton has emerged as a central component of the plant immune system, underpinning not only processes related to cell shape and movement, but also receptor activation and signaling. Using high resolution quantitative imaging techniques, the temporal and spatial changes in the actin microfilament array during diurnal cycling of stomatal guard cells has revealed a highly orchestrated transition from random arrays to ordered bundled filaments. While recent studies have demonstrated that plant stomata close in response to pathogen infection, an evaluation of stimulus-induced changes in actin cytoskeletal dynamics during immune activation in the guard cell, as well as the relationship of these changes to the function of the actin cytoskeleton and stomatal aperture, remains undefined. In the current study, we employed quantitative cell imaging and hierarchical clustering analyses to define the response of the guard cell actin cytoskeleton to pathogen infection and the elicitation of immune signaling. Using this approach, we demonstrate that stomatal-localized actin filaments respond rapidly, and specifically, to both bacterial phytopathogens and purified pathogen elicitors. Notably, we demonstrate that higher order temporal and spatial changes in the filament array show distinct patterns of organization during immune activation, and that changes in the naïve diurnal oscillations of guard cell actin filaments are perturbed by pathogens, and that these changes parallel pathogen-induced stomatal gating. The data presented herein demonstrate the application of a highly tractable and quantifiable method to assign transitions in actin filament organization to the activation of immune signaling in

  15. Quantitative Evaluation of Stomatal Cytoskeletal Patterns during the Activation of Immune Signaling in Arabidopsis thaliana.

    PubMed

    Shimono, Masaki; Higaki, Takumi; Kaku, Hanae; Shibuya, Naoto; Hasezawa, Seiichiro; Day, Brad

    2016-01-01

    Historically viewed as primarily functioning in the regulation of gas and water vapor exchange, it is now evident that stomata serve an important role in plant immunity. Indeed, in addition to classically defined functions related to cell architecture and movement, the actin cytoskeleton has emerged as a central component of the plant immune system, underpinning not only processes related to cell shape and movement, but also receptor activation and signaling. Using high resolution quantitative imaging techniques, the temporal and spatial changes in the actin microfilament array during diurnal cycling of stomatal guard cells has revealed a highly orchestrated transition from random arrays to ordered bundled filaments. While recent studies have demonstrated that plant stomata close in response to pathogen infection, an evaluation of stimulus-induced changes in actin cytoskeletal dynamics during immune activation in the guard cell, as well as the relationship of these changes to the function of the actin cytoskeleton and stomatal aperture, remains undefined. In the current study, we employed quantitative cell imaging and hierarchical clustering analyses to define the response of the guard cell actin cytoskeleton to pathogen infection and the elicitation of immune signaling. Using this approach, we demonstrate that stomatal-localized actin filaments respond rapidly, and specifically, to both bacterial phytopathogens and purified pathogen elicitors. Notably, we demonstrate that higher order temporal and spatial changes in the filament array show distinct patterns of organization during immune activation, and that changes in the naïve diurnal oscillations of guard cell actin filaments are perturbed by pathogens, and that these changes parallel pathogen-induced stomatal gating. The data presented herein demonstrate the application of a highly tractable and quantifiable method to assign transitions in actin filament organization to the activation of immune signaling in

  16. Innate immune-stimulating and immune genes up-regulating activities of three types of alginate from Sargassum siliquosum in Pacific white shrimp, Litopenaeus vannamei.

    PubMed

    Yudiati, Ervia; Isnansetyo, Alim; Murwantoko; Ayuningtyas; Triyanto; Handayani, Christina Retna

    2016-07-01

    The Total Haemocyte Count (THC), phenoloxidase (PO), Superoxide Dismutase (SOD) activity, Phagocytic Activity/Index and Total Protein Plasma (TPP) were examined after feeding the white shrimp Litopenaeus vannamei with diets supplemented with three different types of alginates (acid, calcium and sodium alginates). Immune-related genes expression was evaluated by quantitative Real Time PCR (qRT-PCR). Results indicated that the immune parameters directly increased according to the doses of alginates and time. The 2.0 g kg(-1) of acid and sodium alginate treatments were gave better results. Four immune-related genes expression i.e. LGBP, Toll, Lectin, proPO were up regulated. It is therefore concluded that the supplementation of alginate of Sargassum siliquosum on the diet of L. vannamei enhanced the innate immunity as well as the expression of immune-related genes. It is the first report on the simultaneous evaluation of three alginate types to enhance innate immune parameters and immune-related genes expression in L. vannamei. PMID:26993614

  17. Innate immune-stimulating and immune genes up-regulating activities of three types of alginate from Sargassum siliquosum in Pacific white shrimp, Litopenaeus vannamei.

    PubMed

    Yudiati, Ervia; Isnansetyo, Alim; Murwantoko; Ayuningtyas; Triyanto; Handayani, Christina Retna

    2016-07-01

    The Total Haemocyte Count (THC), phenoloxidase (PO), Superoxide Dismutase (SOD) activity, Phagocytic Activity/Index and Total Protein Plasma (TPP) were examined after feeding the white shrimp Litopenaeus vannamei with diets supplemented with three different types of alginates (acid, calcium and sodium alginates). Immune-related genes expression was evaluated by quantitative Real Time PCR (qRT-PCR). Results indicated that the immune parameters directly increased according to the doses of alginates and time. The 2.0 g kg(-1) of acid and sodium alginate treatments were gave better results. Four immune-related genes expression i.e. LGBP, Toll, Lectin, proPO were up regulated. It is therefore concluded that the supplementation of alginate of Sargassum siliquosum on the diet of L. vannamei enhanced the innate immunity as well as the expression of immune-related genes. It is the first report on the simultaneous evaluation of three alginate types to enhance innate immune parameters and immune-related genes expression in L. vannamei.

  18. Persistent Activation of the Innate Immune Response in Adult Drosophila Following Radiation Exposure During Larval Development.

    PubMed

    Sudmeier, Lisa J; Samudrala, Sai-Suma; Howard, Steven P; Ganetzky, Barry

    2015-11-01

    Cranial radiation therapy (CRT) is an effective treatment for pediatric central nervous system malignancies, but survivors often suffer from neurological and neurocognitive side effects that occur many years after radiation exposure. Although the biological mechanisms underlying these deleterious side effects are incompletely understood, radiation exposure triggers an acute inflammatory response that may evolve into chronic inflammation, offering one avenue of investigation. Recently, we developed a Drosophila model of the neurotoxic side effects of radiation exposure. Here we use this model to investigate the role of the innate immune system in response to radiation exposure. We show that the innate immune response and NF-ĸB target gene expression is activated in the adult Drosophila brain following radiation exposure during larval development, and that this response is sustained in adult flies weeks after radiation exposure. We also present preliminary data suggesting that innate immunity is radioprotective during Drosophila development. Together our data suggest that activation of the innate immune response may be beneficial initially for survival following radiation exposure but result in long-term deleterious consequences, with chronic inflammation leading to impaired neuronal function and viability at later stages. This work lays the foundation for future studies of how the innate immune response is triggered by radiation exposure and its role in mediating the biological responses to radiation. These studies may facilitate the development of strategies to reduce the deleterious side effects of CRT.

  19. Influence of physical activity and nutrition on obesity-related immune function.

    PubMed

    Huang, Chun-Jung; Zourdos, Michael C; Jo, Edward; Ormsbee, Michael J

    2013-01-01

    Research examining immune function during obesity suggests that excessive adiposity is linked to impaired immune responses leading to pathology. The deleterious effects of obesity on immunity have been associated with the systemic proinflammatory profile generated by the secretory molecules derived from adipose cells. These include inflammatory peptides, such as TNF- α , CRP, and IL-6. Consequently, obesity is now characterized as a state of chronic low-grade systemic inflammation, a condition considerably linked to the development of comorbidity. Given the critical role of adipose tissue in the inflammatory process, especially in obese individuals, it becomes an important clinical objective to identify lifestyle factors that may affect the obesity-immune system relationship. For instance, stress, physical activity, and nutrition have each shown to be a significant lifestyle factor influencing the inflammatory profile associated with the state of obesity. Therefore, the purpose of this review is to comprehensively evaluate the impact of lifestyle factors, in particular psychological stress, physical activity, and nutrition, on obesity-related immune function with specific focus on inflammation.

  20. Influence of Physical Activity and Nutrition on Obesity-Related Immune Function

    PubMed Central

    Zourdos, Michael C.; Jo, Edward; Ormsbee, Michael J.

    2013-01-01

    Research examining immune function during obesity suggests that excessive adiposity is linked to impaired immune responses leading to pathology. The deleterious effects of obesity on immunity have been associated with the systemic proinflammatory profile generated by the secretory molecules derived from adipose cells. These include inflammatory peptides, such as TNF-α, CRP, and IL-6. Consequently, obesity is now characterized as a state of chronic low-grade systemic inflammation, a condition considerably linked to the development of comorbidity. Given the critical role of adipose tissue in the inflammatory process, especially in obese individuals, it becomes an important clinical objective to identify lifestyle factors that may affect the obesity-immune system relationship. For instance, stress, physical activity, and nutrition have each shown to be a significant lifestyle factor influencing the inflammatory profile associated with the state of obesity. Therefore, the purpose of this review is to comprehensively evaluate the impact of lifestyle factors, in particular psychological stress, physical activity, and nutrition, on obesity-related immune function with specific focus on inflammation. PMID:24324381

  1. Effect of solar particle event radiation on gastrointestinal tract bacterial translocation and immune activation.

    PubMed

    Ni, Houping; Balint, Klara; Zhou, Yu; Gridley, Daila S; Maks, Casey; Kennedy, Ann R; Weissman, Drew

    2011-04-01

    Space flight conditions within the protection of Earth's gravitational field have been shown to alter immune responses, which could lead to potentially detrimental pathology. An additional risk of extended space travel outside the Earth's gravitational field is the effect of solar particle event (SPE) radiation exposure on the immune system. Organisms that could lead to infection include endogenous, latent viruses, colonizing pathogenics, and commensals, as well as exogenous microbes present in the spacecraft or other astronauts. In this report, the effect of SPE-like radiation on containment of commensal bacteria and the innate immune response induced by its breakdown was investigated at the radiation energies, doses and dose rates expected during an extravehicular excursion outside the Earth's gravitational field. A transient increase in serum lipopolysaccharide was observed 1 day after irradiation and was accompanied by an increase in acute-phase reactants and circulating proinflammatory cytokines, indicating immune activation. Baseline levels were reestablished by 5 days postirradiation. These findings suggest that astronauts exposed to SPE radiation could have impaired containment of colonizing bacteria and associated immune activation.

  2. Effect of Solar Particle Event Radiation on Gastrointestinal Tract Bacterial Translocation and Immune Activation

    PubMed Central

    Ni, Houping; Balint, Klara; Zhou, Yu; Gridley, Daila S.; Maks, Casey; Kennedy, Ann R.; Weissman, Drew

    2013-01-01

    Space flight conditions within the protection of Earth’s gravitational field have been shown to alter immune responses, which could lead to potentially detrimental pathology. An additional risk of extended space travel outside the Earth’s gravitational field is the effect of solar particle event (SPE) radiation exposure on the immune system. Organisms that could lead to infection include endogenous, latent viruses, colonizing pathogenics, and commensals, as well as exogenous microbes present in the spacecraft or other astronauts. In this report, the effect of SPE-like radiation on containment of commensal bacteria and the innate immune response induced by its breakdown was investigated at the radiation energies, doses and dose rates expected during an extravehicular excursion outside the Earth’s gravitational field. A transient increase in serum lipopolysaccharide was observed 1 day after irradiation and was accompanied by an increase in acute-phase reactants and circulating proinflammatory cytokines, indicating immune activation. Baseline levels were reestablished by 5 days postirradiation. These findings suggest that astronauts exposed to SPE radiation could have impaired containment of colonizing bacteria and associated immune activation. PMID:21294608

  3. Persistent Activation of the Innate Immune Response in Adult Drosophila Following Radiation Exposure During Larval Development

    PubMed Central

    Sudmeier, Lisa J.; Samudrala, Sai-Suma; Howard, Steven P.; Ganetzky, Barry

    2015-01-01

    Cranial radiation therapy (CRT) is an effective treatment for pediatric central nervous system malignancies, but survivors often suffer from neurological and neurocognitive side effects that occur many years after radiation exposure. Although the biological mechanisms underlying these deleterious side effects are incompletely understood, radiation exposure triggers an acute inflammatory response that may evolve into chronic inflammation, offering one avenue of investigation. Recently, we developed a Drosophila model of the neurotoxic side effects of radiation exposure. Here we use this model to investigate the role of the innate immune system in response to radiation exposure. We show that the innate immune response and NF-ĸB target gene expression is activated in the adult Drosophila brain following radiation exposure during larval development, and that this response is sustained in adult flies weeks after radiation exposure. We also present preliminary data suggesting that innate immunity is radioprotective during Drosophila development. Together our data suggest that activation of the innate immune response may be beneficial initially for survival following radiation exposure but result in long-term deleterious consequences, with chronic inflammation leading to impaired neuronal function and viability at later stages. This work lays the foundation for future studies of how the innate immune response is triggered by radiation exposure and its role in mediating the biological responses to radiation. These studies may facilitate the development of strategies to reduce the deleterious side effects of CRT. PMID:26333838

  4. Protumor Activities of the Immune Response: Insights in the Mechanisms of Immunological Shift, Oncotraining, and Oncopromotion

    PubMed Central

    Chimal-Ramírez, G. K.; Espinoza-Sánchez, N. A.; Fuentes-Pananá, E. M.

    2013-01-01

    Experimental and clinical studies indicate that cells of the innate and adaptive immune system have both anti- and pro-tumor activities. This dual role of the immune system has led to a conceptual shift in the role of the immune system's regulation of cancer, in which immune-tumor cell interactions are understood as a dynamic process that comprises at least five phases: immunosurveillance, immunoselection, immunoescape, oncotraining, and oncopromotion. The tumor microenvironment shifts immune cells to perform functions more in tune with the tumor needs (oncotraining); these functions are related to chronic inflammation and tissue remodeling activities. Among them are increased proliferation and survival, increased angiogenesis and vessel permeability, protease secretion, acquisition of migratory mesenchymal characteristics, and self-renewal properties that altogether promote tumor growth and metastasis (oncopromotion). Important populations in all these pro-tumor processes are M2 macrophages, N2 neutrophils, regulatory T cells, and myeloid derived suppressor cells; the main effectors molecules are CSF-1, IL-6, metalloproteases, VEGF, PGE-2, TGF-β, and IL-10. Cancer prognosis correlates with densities and concentrations of protumoral populations and molecules, providing ideal targets for the intelligent design of directed preventive or anticancer therapies. PMID:23577028

  5. Autoimmune activation toward embryo implantation is rare in immune-privileged human endometrium.

    PubMed

    Haller-Kikkatalo, Kadri; Altmäe, Signe; Tagoma, Aili; Uibo, Raivo; Salumets, Andres

    2014-09-01

    Human embryo implantation represents embryo apposition, adhesion to the endometrial epithelium, and invasion into the stromal extracellular matrix within 1 to 2 days during days 6 to 9 after ovulation. The major molecular mechanisms mediating implantation include adhesion molecules, including mucins, selectins, integrins, and cadherins; extracellular matrix components, such as laminins and collagens and their degrading enzymes; phospholipids and immune regulatory molecules, including prostaglandins, cytokines; and immunosuppressive molecules expressed by invasive trophoblasts and endometrial cells. Many of these molecules are the targets for autoimmune reactions in autoimmune diseases and cancer; however, the relevance of those in immune-mediated implantation failure has not been defined. In this review, we will describe the molecules involved in 2-day event of human embryo implantation, which may also be involved in immune system activation and subsequently cause immune-mediated implantation failure. We speculate that the data in the literature are limited concerning antiendometrial antibodies because the endometrium might be taken as an immune-privileged site that avoids autoimmune activation that might harm the implantation process. Antibodies affecting human fertility in ways other than impairing implantation are outside the scope of the current article and will not be discussed. PMID:24959819

  6. Maternal and Umbilical Cord Blood Levels of Zinc and Copper in Active Labor Versus Elective Caesarean Delivery at Khartoum Hospital, Sudan.

    PubMed

    Elhadi, Alaeldin; Rayis, Duria A; Abdullahi, Hala; Elbashir, Leana M; Ali, Naji I; Adam, Ishag

    2016-01-01

    A case-control study was conducted in Khartoum Hospital Sudan to determine maternal and umbilical cord blood levels of zinc and copper in active labor versus elective cesarean delivery. Cases were women delivered vaginally and controls were women delivered by elective cesarean (before initiation of labor). Paired maternal and cord zinc and copper were measured using atomic absorption spectrophotometry. The two groups (52 paired maternal and cord in each arm) were well matched in their basic characteristics. In comparison with cesarean delivery, the median (interquartile range) of both maternal [87.0 (76.1-111.4) vs. 76.1 (65.2-88.3) μg/dL, P = 0.004] and cord zinc [97.8 (87.0-114.1) vs. 81.5(65.2-110.2) μg/dL P = 0.034] levels were significantly higher in the vaginal delivery. While there was no significant difference in the maternal copper [78.8 (48.1-106.1) vs. 92.4 (51.9-114.9) μg/dL, P = 0.759], the cord copper [43.5(29.9-76.1) vs. 32.2(21.7-49.6) μg/dL, P = 0.019] level was significantly higher in vaginal delivery. There was no significant correlation between zinc (both maternal and cord) and copper. While the cord zinc was significantly correlated with maternal zinc, there was no significant correlation between maternal and cord copper. The current study showed significantly higher levels of maternal and cord zinc and cord copper in women who delivered vaginally compared with caesarean delivery.

  7. The Effect of Maternal Stress Activation on the Offspring during Lactation in Light of Vasopressin

    PubMed Central

    2014-01-01

    Although it is obvious that preconceptional effects as well as stressors during pregnancy profoundly influence the progeny, the lactation period seems to be at least as important. Here we summarize how maternal stressors during the lactation period affect the offspring. As vasopressin is one of the crucial components both for stress adaptation and social behavior, special emphasis was given to this neuropeptide. We can conclude that stressing the mother does not have the same acute effect on the hypothalamo-pituitary-adrenocortical axis (as the main target of stress adaptation) of the pups as stressing the pups, but later endocrine and behavioral consequences can be similar. Vasopressin plays a role in acute and later consequences of perinatal stressor applied either to the mother or to the offspring, thereby contributing to transmitting the mothers' stress to the progeny. This mother-infant interaction does not necessarily mean a direct transmission of molecules, but rather is the result of programming the brain development through changes in maternal behavior. Thus, there is a time lag between maternal stress and stress-related changes in the offspring. The interactions are bidirectional as not only stress in the dam but also stress in the progeny has an effect on nursing. PMID:24550698

  8. Passive immunization and active vaccination against Hendra and Nipah viruses.

    PubMed

    Broder, C C

    2013-01-01

    Hendra virus and Nipah virus are viral zoonoses first recognized in the mid and late 1990's and are now categorized as the type species of the genus Henipavirus within the family Paramyxoviridae. Their broad species tropism together with their capacity to cause severe and often fatal disease in both humans and animals make Hendra and Nipah "overlap agents" and significant biosecurity threats. The development of effective vaccination strategies to prevent or treat henipavirus infection and disease has been an important area of research. Here, henipavirus active and passive vaccination strategies that have been examined in animal challenge models of Hendra and Nipah virus disease are summarized and discussed.

  9. Activated T cells sustain myeloid-derived suppressor cell-mediated immune suppression

    PubMed Central

    Damuzzo, Vera; Francescato, Samuela; Pozzuoli, Assunta; Berizzi, Antonio; Mocellin, Simone; Rossi, Carlo Riccardo; Bronte, Vincenzo; Mandruzzato, Susanna

    2016-01-01

    The expansion of myeloid derived suppressor cells (MDSCs), a suppressive population able to hamper the immune response against cancer, correlates with tumor progression and overall survival in several cancer types. We have previously shown that MDSCs can be induced in vitro from precursors present in the bone marrow and observed that these cells are able to actively proliferate in the presence of activated T cells, whose activation level is critical to drive the suppressive activity of MDSCs. Here we investigated at molecular level the mechanisms involved in the interplay between MDSCs and activated T cells. We found that activated T cells secrete IL-10 following interaction with MDSCs which, in turn, activates STAT3 phosphorylation on MDSCs then leading to B7-H1 expression. We also demonstrated that B7-H1+ MDSCs are responsible for immune suppression through a mechanism involving ARG-1 and IDO expression. Finally, we show that the expression of ligands B7-H1 and MHC class II both on in vitro-induced MDSCs and on MDSCs in the tumor microenvironment of cancer patients is paralleled by an increased expression of their respective receptors PD-1 and LAG-3 on T cells, two inhibitory molecules associated with T cell dysfunction. These findings highlight key molecules and interactions responsible for the extensive cross-talk between MDSCs and activated T cells that are at the basis of immune suppression. PMID:26700461

  10. Activated T cells sustain myeloid-derived suppressor cell-mediated immune suppression.

    PubMed

    Pinton, Laura; Solito, Samantha; Damuzzo, Vera; Francescato, Samuela; Pozzuoli, Assunta; Berizzi, Antonio; Mocellin, Simone; Rossi, Carlo Riccardo; Bronte, Vincenzo; Mandruzzato, Susanna

    2016-01-12

    The expansion of myeloid derived suppressor cells (MDSCs), a suppressive population able to hamper the immune response against cancer, correlates with tumor progression and overall survival in several cancer types. We have previously shown that MDSCs can be induced in vitro from precursors present in the bone marrow and observed that these cells are able to actively proliferate in the presence of activated T cells, whose activation level is critical to drive the suppressive activity of MDSCs. Here we investigated at molecular level the mechanisms involved in the interplay between MDSCs and activated T cells. We found that activated T cells secrete IL-10 following interaction with MDSCs which, in turn, activates STAT3 phosphorylation on MDSCs then leading to B7-H1 expression. We also demonstrated that B7-H1+ MDSCs are responsible for immune suppression through a mechanism involving ARG-1 and IDO expression. Finally, we show that the expression of ligands B7-H1 and MHC class II both on in vitro-induced MDSCs and on MDSCs in the tumor microenvironment of cancer patients is paralleled by an increased expression of their respective receptors PD-1 and LAG-3 on T cells, two inhibitory molecules associated with T cell dysfunction. These findings highlight key molecules and interactions responsible for the extensive cross-talk between MDSCs and activated T cells that are at the basis of immune suppression.

  11. Evaluation of in vivo immune complex formation and complement activation in patients receiving intravenous streptokinase.

    PubMed Central

    Freysdottir, J; Ormarsdottir, S; Sigfusson, A

    1993-01-01

    The usefulness of several different methods for detecting immune complex formation and complement activation in the circulation were applied to samples from patients receiving intravenous Streptokinase therapy for myocardial infarction. Streptokinase is a foreign antigen and can cause immune reactions. We collected samples from 13 patients, before Streptokinase administration (baseline), at the end of infusion (1 h), 12 h later and on day 7. We measured IgG containing immune complexes (IgG-IC), free C3d and antibodies to Streptokinase by ELISA, and CR1, C3d and C4d on erythrocytes by flow cytometric assay. Antibodies to Streptokinase are common, as all but two of the patients had measurable antibody levels. During Streptokinase treatment there was a drop in antibody levels, most prominent in those patients who had high baseline levels. At the same time increased levels of free C3d and erythrocyte-bound C3d were observed. After 12 h free C3d was usually back to baseline level, but C3d on erythrocytes was still raised. These data indicate the formation of Streptokinase immune complexes in patients with high Streptokinase antibody levels, and show that these complexes are cleared rapidly from the circulation, leaving more persistent signs of complement activation. We conclude that free C3d is a good indicator of ongoing complement activation, whereas C3d on erythrocytes indicates that complement activation has recently taken place. PMID:8222319

  12. Scavenging iron: a novel mechanism of plant immunity activation by microbial siderophores.

    PubMed

    Aznar, Aude; Chen, Nicolas W G; Rigault, Martine; Riache, Nassima; Joseph, Delphine; Desmaële, Didier; Mouille, Grégory; Boutet, Stéphanie; Soubigou-Taconnat, Ludivine; Renou, Jean-Pierre; Thomine, Sébastien; Expert, Dominique; Dellagi, Alia

    2014-04-01

    Siderophores are specific ferric iron chelators synthesized by virtually all microorganisms in response to iron deficiency. We have previously shown that they promote infection by the phytopathogenic enterobacteria Dickeya dadantii and Erwinia amylovora. Siderophores also have the ability to activate plant immunity. We have used complete Arabidopsis transcriptome microarrays to investigate the global transcriptional modifications in roots and leaves of Arabidopsis (Arabidopsis thaliana) plants after leaf treatment with the siderophore deferrioxamine (DFO). Physiological relevance of these transcriptional modifications was validated experimentally. Immunity and heavy-metal homeostasis were the major processes affected by DFO. These two physiological responses could be activated by a synthetic iron chelator ethylenediamine-di(o-hydroxyphenylacetic) acid, indicating that siderophores eliciting activities rely on their strong iron-chelating capacity. DFO was able to protect Arabidopsis against the pathogenic bacterium Pseudomonas syringae pv tomato DC3000. Siderophore treatment caused local modifications of iron distribution in leaf cells visible by ferrocyanide and diaminobenzidine-H₂O₂ staining. Metal quantifications showed that DFO causes a transient iron and zinc uptake at the root level, which is presumably mediated by the metal transporter iron regulated transporter1 (IRT1). Defense gene expression and callose deposition in response to DFO were compromised in an irt1 mutant. Consistently, plant susceptibility to D. dadantii was increased in the irt1 mutant. Our work shows that iron scavenging is a unique mechanism of immunity activation in plants. It highlights the strong relationship between heavy-metal homeostasis and immunity. PMID:24501001

  13. Scavenging Iron: A Novel Mechanism of Plant Immunity Activation by Microbial Siderophores1[C][W

    PubMed Central

    Aznar, Aude; Chen, Nicolas W.G.; Rigault, Martine; Riache, Nassima; Joseph, Delphine; Desmaële, Didier; Mouille, Grégory; Boutet, Stéphanie; Soubigou-Taconnat, Ludivine; Renou, Jean-Pierre; Thomine, Sébastien; Expert, Dominique; Dellagi, Alia

    2014-01-01

    Siderophores are specific ferric iron chelators synthesized by virtually all microorganisms in response to iron deficiency. We have previously shown that they promote infection by the phytopathogenic enterobacteria Dickeya dadantii and Erwinia amylovora. Siderophores also have the ability to activate plant immunity. We have used complete Arabidopsis transcriptome microarrays to investigate the global transcriptional modifications in roots and leaves of Arabidopsis (Arabidopsis thaliana) plants after leaf treatment with the siderophore deferrioxamine (DFO). Physiological relevance of these transcriptional modifications was validated experimentally. Immunity and heavy-metal homeostasis were the major processes affected by DFO. These two physiological responses could be activated by a synthetic iron chelator ethylenediamine-di(o-hydroxyphenylacetic) acid, indicating that siderophores eliciting activities rely on their strong iron-chelating capacity. DFO was able to protect Arabidopsis against the pathogenic bacterium Pseudomonas syringae pv tomato DC3000. Siderophore treatment caused local modifications of iron distribution in leaf cells visible by ferrocyanide and diaminobenzidine-H2O2 staining. Metal quantifications showed that DFO causes a transient iron and zinc uptake at the root level, which is presumably mediated by the metal transporter iron regulated transporter1 (IRT1). Defense gene expression and callose deposition in response to DFO were compromised in an irt1 mutant. Consistently, plant susceptibility to D. dadantii was increased in the irt1 mutant. Our work shows that iron scavenging is a unique mechanism of immunity activation in plants. It highlights the strong relationship between heavy-metal homeostasis and immunity. PMID:24501001

  14. Maternal inflammation activated ROS-p38 MAPK predisposes offspring to heart damages caused by isoproterenol via augmenting ROS generation

    PubMed Central

    Zhang, Qi; Deng, Yafei; Lai, Wenjing; Guan, Xiao; Sun, Xiongshan; Han, Qi; Wang, Fangjie; Pan, Xiaodong; Ji, Yan; Luo, Hongqin; Huang, Pei; Tang, Yuan; Gu, Liangqi; Dan, Guorong; Yu, Jianhua; Namaka, Michael; Zhang, Jianxiang; Deng, Youcai; Li, Xiaohui

    2016-01-01

    Maternal inflammation contributes to the increased incidence of adult cardiovascular disease. The current study investigated the susceptibility of cardiac damage responding to isoproterenol (ISO) in adult offspring that underwent maternal inflammation (modeled by pregnant Sprague-Dawley rats with lipopolysaccharides (LPS) challenge). We found that 2 weeks of ISO treatment in adult offspring of LPS-treated mothers led to augmented heart damage, characterized by left-ventricular systolic dysfunction, cardiac hypertrophy and myocardial fibrosis. Mechanistically, prenatal exposure to LPS led to up-regulated expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, antioxidant enzymes, and p38 MAPK activity in left ventricular of adult offspring at resting state. ISO treatment exaggerated ROS generation, p38 MAPK activation but down-regulated reactive oxygen species (ROS) elimination capacity in the left ventricular of offspring from LPS-treated mothers, while antioxidant N-acetyl-L-cysteine (NAC) reversed these changes together with improved cardiac functions. The p38 inhibitor SB202190 alleviated the heart damage only via inhibiting the expression of NADPH oxidases. Collectively, our data demonstrated that prenatal inflammation programs pre-existed ROS activation in the heart tissue, which switches on the early process of oxidative damages on heart rapidly through a ROS-p38 MAPK-NADPH oxidase-ROS positive feedback loop in response to a myocardial hypertrophic challenge in adulthood. PMID:27443826

  15. Immune regulatory activities of fowlicidin-1, a cathelicidin host defense peptide.

    PubMed

    Bommineni, Yugendar R; Pham, Giang H; Sunkara, Lakshmi T; Achanta, Mallika; Zhang, Guolong

    2014-05-01

    Appropriate modulation of immunity is beneficial in antimicrobial therapy and vaccine development. Host defense peptides (HDPs) constitute critically important components of innate immunity with both antimicrobial and immune regulatory activities. We previously showed that a chicken HDP, namely fowlicidin-1(6-26), has potent antibacterial activities in vitro and in vivo. Here we further revealed that fowl-1(6-26) possesses strong immunomodulatory properties. The peptide is chemotactic specifically to neutrophils, but not monocytes or lymphocytes, after injected into the mouse peritoneum. Fowl-1(6-26) also has the capacity to activate macrophages by inducing the expression of inflammatory mediators including IL-1β, CCL2, and CCL3. However, unlike bacterial lipopolysaccharide that triggers massive production of inflammatory cytokines and chemokines, fowl-1(6-26) only marginally increased their expression in mouse RAW264.7 macrophages. Additionally, fowl-1(6-26) enhanced the surface expression of MHC II and CD86 on RAW264.7 cells, suggesting that it may facilitate development of adaptive immune response. Indeed, co-immunization of mice with chicken ovalbumin (OVA) and fowl-1(6-26) augmented both OVA-specific IgG1 and IgG2a titers, relative to OVA alone. We further showed that fowl-1(6-26) is capable of preventing a methicillin-resistant Staphylococcus aureus (MRSA) infection due to its enhancement of host defense. All mice survived from an otherwise lethal infection when the peptide was administered 1-2 days prior to MRSA infection, and 50% mice were protected if receiving the peptide 4 days before infection. Taken together, with a strong capacity to stimulate innate and adaptive immunity, fowl-1(6-26) may have potential to be developed as a novel antimicrobial and a vaccine adjuvant.

  16. Ubiquitin in the activation and attenuation of innate antiviral immunity

    PubMed Central

    Heaton, Steven M.

    2016-01-01

    Viral infection activates danger signals that are transmitted via the retinoic acid–inducible gene 1–like receptor (RLR), nucleotide-binding oligomerization domain-like receptor (NLR), and Toll-like receptor (TLR) protein signaling cascades. This places host cells in an antiviral posture by up-regulating antiviral cytokines including type-I interferon (IFN-I). Ubiquitin modifications and cross-talk between proteins within these signaling cascades potentiate IFN-I expression, and inversely, a growing number of viruses are found to weaponize the ubiquitin modification system to suppress IFN-I. Here we review how host- and virus-directed ubiquitin modification of proteins in the RLR, NLR, and TLR antiviral signaling cascades modulate IFN-I expression. PMID:26712804

  17. Intracellular sensing of complement C3 activates cell autonomous immunity

    PubMed Central

    Tam, Jerry C.H.; Bidgood, Susanna R.; McEwan, William A.; James, Leo C.

    2014-01-01

    Pathogens traverse multiple barriers during infection including cell membranes. Here we show that during this transition pathogens carry covalently attached complement C3 into the cell, triggering immediate signalling and effector responses. Sensing of C3 in the cytosol activates MAVS-dependent signalling cascades and induces proinflammatory cytokine secretion. C3 also flags viruses for rapid proteasomal degradation, thereby preventing their replication. This system can detect both viral and bacterial pathogens but is antagonized by enteroviruses, such as rhinovirus and poliovirus, which cleave C3 using their 3C protease. The antiviral Rupintrivir inhibits 3C protease and prevents C3 cleavage, rendering enteroviruses susceptible to intracellular complement sensing. Thus, complement C3 allows cells to detect and disable pathogens that have invaded the cytosol. PMID:25190799

  18. Formation of disulfide bonds in insect prophenoloxidase enhances immunity through improving enzyme activity and stability.

    PubMed

    Lu, Anrui; Peng, Qin; Ling, Erjun

    2014-06-01

    Type 3 copper proteins, including insect prophenoloxidase (PPO), contain two copper atoms in the active site pocket and can oxidize phenols. Insect PPO plays an important role in immunity. Insects and other invertebrates show limited recovery from pathogen invasion and wounds if phenoloxidase (PO) activity is low. In most insect PPOs, two disulfide bonds are present near the C-terminus. However, in Pimpla hypochondriaca (a parasitoid wasp), each PPO contains one disulfide bond. We thus questioned whether the formation of two sulfide bonds in insect PPOs improved protein stability and/or increased insect innate immunity over time. Using Drosophila melanogaster PPO1 as a model, one or two disulfide bonds were deleted to evaluate the importance of disulfide bonds in insect immunity. rPPO1 and mutants lacking disulfide bonds could be expressed and showed PO activity. However, the PO activities of mutants lacking one or two disulfide bonds significantly decreased. Deletion of disulfide bonds also reduced PPO thermostability. Furthermore, antibacterial activities against Escherichia coli and Bacillus subtilis significantly decreased when disulfide bonds were deleted. Therefore, the formation of two disulfide bond(s) in insect PPO enhances antibacterial activity by increasing PO activity and stability.

  19. Design of host defence peptides for antimicrobial and immunity enhancing activities.

    PubMed

    McPhee, Joseph B; Scott, Monisha G; Hancock, Robert E W

    2005-05-01

    Host defense peptides are a vital component of the innate immune systems of humans, other mammals, amphibians, and arthropods. The related cationic antimicrobial peptides are also produced by many species of bacteria and function as part of the antimicrobial arsenal to help the producing organism reduce competition for resources from sensitive species. The antimicrobial activities of many of these peptides have been extensively characterized and the structural requirements for these activities are also becoming increasingly clear. In addition to their known antimicrobial role, many host defense peptides are also involved in a plethora of immune functions in the host. In this review, we examine the role of structure in determining antimicrobial activity of certain prototypical cationic peptides and ways that bacteria have evolved to usurp these activities. We also review recent literature on what structural components are related to these immunomodulatory effects. It must be stressed however that these studies, and the area of peptide research, are still in their infancy.

  20. Mechanistic insights on immunosenescence and chronic immune activation in HIV-tuberculosis co-infection

    PubMed Central

    Shankar, Esaki M; Velu, Vijayakumar; Kamarulzaman, Adeeba; Larsson, Marie

    2015-01-01

    Immunosenescence is marked by accelerated degradation of host immune responses leading to the onset of opportunistic infections, where senescent T cells show remarkably higher ontogenic defects as compared to healthy T cells. The mechanistic association between T-cell immunosenescence and human immunodeficiency virus (HIV) disease progression, and functional T-cell responses in HIV-tuberculosis (HIV-TB) co-infection remains to be elaborately discussed. Here, we discussed the association of immunosenescence and chronic immune activation in HIV-TB co-infection and reviewed the role played by mediators of immune deterioration in HIV-TB co-infection necessitating the importance of designing therapeutic strategies against HIV disease progression and pathogenesis. PMID:25674514

  1. Supramolecular organizing centers (SMOCs) as signaling machines in innate immune activation

    PubMed Central

    Qi, QIAO; Hao, WU

    2016-01-01

    Innate immunity offers the first line of defense against infections and other types of danger such as tumorigenesis. Its discovery provides tremendous therapeutic opportunities for numerous human diseases. Delving into the structural basis of signal transduction by innate immune receptors, our lab has recently helped to establish the new paradigm in which innate immune receptors transduce ligand-binding signals through formation of higher-order assemblies containing intracellular adapters, signaling enzymes and their substrates. These large signalosome assemblies may be visible under light microscopy as punctate structures in the μm scale, connecting to the underlying molecular structures in the nm scale. They drive proximity-induced enzyme activation, and provide a mechanism for signaling amplification by nucleated polymerization. These supramolecular signaling complexes also open new questions on their cellular organization and mode of regulation, pose challenges to our methodology, and afford valuable implications in drug discovery against these medically important pathways. PMID:26511517

  2. The Dual Role of Exosomes in Hepatitis A and C Virus Transmission and Viral Immune Activation.

    PubMed

    Longatti, Andrea

    2015-12-17

    Exosomes are small nanovesicles of about 100 nm in diameter that act as intercellular messengers because they can shuttle RNA, proteins and lipids between different cells. Many studies have found that exosomes also play various roles in viral pathogenesis. Hepatitis A virus (HAV; a picornavirus) and Hepatitis C virus (HCV; a flavivirus) two single strand plus-sense RNA viruses, in particular, have been found to use exosomes for viral transmission thus evading antibody-mediated immune responses. Paradoxically, both viral exosomes can also be detected by plasmacytoid dendritic cells (pDCs) leading to innate immune activation and type I interferon production. This article will review recent findings regarding these two viruses and outline how exosomes are involved in their transmission and immune sensing.

  3. Active immunization of rats with cumulus-free mouse ova: induction of infertility and antibody titers.

    PubMed

    Aitken, R J; Richardson, D W

    1981-04-01

    Active immunization of rats with cross-reacting zona pellucida antigens derived from cumulus-free mouse ova resulted in the induction in fertility without adverse side effects. Half of the immunized animals never regained their fertility despite repeated matings with fertile males. Two of the remaining animals conceived when antibody titers fell to basal levels and gave birth to litters of normal healthy young. Post mortem examination of immunized animals 24 hours after finding sperm in the vaginal smears resulted in the recovery of tubal ova exhibiting the presence of a precipitate on the outer surface of the zona pellucida. Some of these ova appeared to have been fertilized, suggesting that anti-zona antibodies may also inhibit fertility through a post-fertilization mechanism of action. PMID:7288384

  4. The Dual Role of Exosomes in Hepatitis A and C Virus Transmission and Viral Immune Activation

    PubMed Central

    Longatti, Andrea

    2015-01-01

    Exosomes are small nanovesicles of about 100 nm in diameter that act as intercellular messengers because they can shuttle RNA, proteins and lipids between different cells. Many studies have found that exosomes also play various roles in viral pathogenesis. Hepatitis A virus (HAV; a picornavirus) and Hepatitis C virus (HCV; a flavivirus) two single strand plus-sense RNA viruses, in particular, have been found to use exosomes for viral transmission thus evading antibody-mediated immune responses. Paradoxically, both viral exosomes can also be detected by plasmacytoid dendritic cells (pDCs) leading to innate immune activation and type I interferon production. This article will review recent findings regarding these two viruses and outline how exosomes are involved in their transmission and immune sensing. PMID:26694453

  5. Activation of NOD receptors by Neisseria gonorrhoeae modulates the innate immune response.

    PubMed

    Mavrogiorgos, Nikolaos; Mekasha, Samrawit; Yang, Yibin; Kelliher, Michelle A; Ingalls, Robin R

    2014-05-01

    NOD1 and NOD2 are members of the NOD-like receptor family of cytosolic pattern recognition receptors that recognize specific fragments of the bacterial cell wall component peptidoglycan. Neisseria species are unique amongst Gram-negative bacteria in that they turn over large amounts of peptidoglycan during growth. We examined the ability of NOD1 and NOD2 to recognize Neisseria gonorrhoeae, and determined the role of NOD-dependent signaling in regulating the immune response to gonococcal infection. Gonococci, as well as conditioned medium from mid-logarithmic phase grown bacteria, were capable of activating both human NOD1 and NOD2, as well as mouse NOD2, leading to the activation of the transcription factor NF-κB and polyubiquitination of the adaptor receptor-interacting serine-threonine kinase 2. We identified a number of cytokines and chemokines that were differentially expressed in wild type versus NOD2-deficient macrophages in response to gonococcal infection. Moreover, NOD2 signaling up-regulated complement pathway components and cytosolic nucleic acid sensors, suggesting a broad impact of NOD activation on innate immunity. Thus, NOD1 and NOD2 are important intracellular regulators of the immune response to infection with N. gonorrhoeae. Given the intracellular lifestyle of this pathogen, we believe these cytosolic receptors may provide a key innate immune defense mechanism for the host during gonococcal infection. PMID:23884094

  6. mTORC1-Activated Monocytes Increase Tregs and Inhibit the Immune Response to Bacterial Infections

    PubMed Central

    Tu, Huaijun; Guo, Wei; Wang, Shixuan; Xue, Ting; Yang, Fei; Zhang, Xiaoyan; Yang, Yazhi; Wan, Qian; Shi, Zhexin; Zhan, Xulong

    2016-01-01

    The TSC1/2 heterodimer, a key upstream regulator of the mTOR, can inhibit the activation of mTOR, which plays a critical role in immune responses after bacterial infections. Monocytes are an innate immune cell type that have been shown to be involved in bacteremia. However, how the mTOR pathway is involved in the regulation of monocytes is largely unknown. In our study, TSC1 KO mice and WT mice were infected with E. coli. When compared to WT mice, we found higher mortality, greater numbers of bacteria, decreased expression of coactivators in monocytes, increased numbers of Tregs, and decreased numbers of effector T cells in TSC1 KO mice. Monocytes obtained from TSC1 KO mice produced more ROS, IL-6, IL-10, and TGF-β and less IL-1, IFN-γ, and TNF-α. Taken together, our results suggest that the inhibited immune functioning in TSC1 KO mice is influenced by mTORC1 activation in monocytes. The reduced expression of coactivators resulted in inhibited effector T cell proliferation. mTORC1-activated monocytes are harmful during bacterial infections. Therefore, inhibiting mTORC1 signaling through rapamycin administration could rescue the harmful aspects of an overactive immune response, and this knowledge provides a new direction for clinical therapy. PMID:27746591

  7. ACTIVE IMMUNITY PRODUCED BY SO CALLED BALANCED OR NEUTRAL MIXTURES OF DIPHTHERIA TOXIN AND ANTITOXIN.

    PubMed

    Smith, T

    1909-03-01

    The foregoing and earlier data taken together demonstrate that an active immunity lasting several years can be produced in guinea-pigs, by the injection of toxin-antitoxin mixtures which have no recognizable harmful effect either immediate or remote. They also show, what might have been anticipated, that under the same conditions mixtures which produce local lesions and which, therefore, contain an excess of toxin produce a much higher degree of immunity than the neutral mixtures, and that an excess of antitoxin reduces the possibility of producing an active immunity, and may extinguish it altogether. There is, therefore, a certain definite relation between the components of the mixture and the degree of immunity producible. Furthermore, toxin-antitoxin mixtures do not change materially within five days at room temperature. They are apparently more efficacious at the end of forty-eight hours than immediately after preparation. The experiments finally prove that a relatively high degree of active immunity can be induced by a harmless procedure, whereas the use of toxin alone leading to very severe local lesions is incapable of producing more than an insignificant protection. The method, therefore, invites further tests in regard to its ultimate applicability to the human being. Unless the subcutis of the guinea-pig reacts to toxin-antitoxin mixtures in a manner peculiar to itself, a practical, easily controlled method for active immunization can be worked out which should afford a larger protection than the serum alone and avoid the complications associated with horse serum. That proportion of toxin and antitoxin which would produce the highest desirable immunity consistent with the least discomfort would have to be carefully worked out for the human subject. From the nature of the immunity induced it is obvious, however, that such a method of immunization cannot take the place of a large dose of antitoxin in exposed individuals who must be protected at once. It

  8. Inorganic nanoparticles and the immune system: detection, selective activation and tolerance

    NASA Astrophysics Data System (ADS)

    Bastús, Neus G.; Sánchez-Tilló, Ester; Pujals, Silvia; Comenge, Joan; Giralt, Ernest; Celada, Antonio; Lloberas, Jorge; Puntes, Victor F.

    2012-03-01

    The immune system is the responsible for body integrity and prevention of external invasion. On one side, nanoparticles are no triggers that the immune system is prepared to detect, on the other side it is known that foreign bodies, not only bacteria, viruses and parasites, but also inorganic matter, can cause various pathologies such as silicosis, asbestosis or inflammatory reactions. Therefore, nanoparticles entering the body, after interaction with proteins, will be either recognized as self-agents or detected by the immune system, encompassing immunostimulation or immunosuppression responses. The nature of these interactions seems to be dictated not specially by the composition of the material but by modifications of NP coating (composition, surface charge and structure). Herein, we explore the use of gold nanoparticles as substrates to carry multifunctional ligands to manipulate the immune system in a controlled manner, from undetection to immunostimulation. Murine bone marrow macrophages can be activated with artificial nanometric objects consisting of a gold nanoparticle functionalized with peptides. In the presence of some conjugates, macrophage proliferation was stopped and pro-inflammatory cytokines were induced. The biochemical type of response depended on the type of conjugated peptide and was correlated with the degree of ordering in the peptide coating. These findings help to illustrate the basic requirements involved in medical NP conjugate design to either activate the immune system or hide from it, in order to reach their targets before being removed by phagocytes. Additionally, it opens up the possibility to modulate the immune response in order to suppress unwanted responses resulting from autoimmunity, or allergy or to stimulate protective responses against pathogens.

  9. 22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. 40.25 Section 40.25 Foreign Relations DEPARTMENT OF... involved in serious criminal activity who have asserted immunity from prosecution....

  10. 22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. 40.25 Section 40.25 Foreign Relations DEPARTMENT OF... involved in serious criminal activity who have asserted immunity from prosecution....

  11. 22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. 40.25 Section 40.25 Foreign Relations DEPARTMENT OF... involved in serious criminal activity who have asserted immunity from prosecution....

  12. 22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. 40.25 Section 40.25 Foreign Relations DEPARTMENT OF... involved in serious criminal activity who have asserted immunity from prosecution....

  13. 22 CFR 40.25 - Certain aliens involved in serious criminal activity who have asserted immunity from prosecution...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Certain aliens involved in serious criminal activity who have asserted immunity from prosecution. 40.25 Section 40.25 Foreign Relations DEPARTMENT OF... involved in serious criminal activity who have asserted immunity from prosecution....

  14. Methylation of NR3C1 is related to maternal PTSD, parenting stress and maternal medial prefrontal cortical activity in response to child separation among mothers with histories of violence exposure

    PubMed Central

    Schechter, Daniel S.; Moser, Dominik A.; Paoloni-Giacobino, Ariane; Stenz, Ludwig; Gex-Fabry, Marianne; Aue, Tatjana; Adouan, Wafae; Cordero, María I.; Suardi, Francesca; Manini, Aurelia; Sancho Rossignol, Ana; Merminod, Gaëlle; Ansermet, Francois; Dayer, Alexandre G.; Rusconi Serpa, Sandra

    2015-01-01

    Prior research has shown that mothers with Interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) report greater difficulty in parenting their toddlers. Relative to their frequent early exposure to violence and maltreatment, these mothers display dysregulation of their hypothalamic pituitary adrenal axis (HPA-axis), characterized by hypocortisolism. Considering methylation of the promoter region of the glucocorticoid receptor gene NR3C1 as a marker for HPA-axis functioning, with less methylation likely being associated with less circulating cortisol, the present study tested the hypothesis that the degree of methylation of this gene would be negatively correlated with maternal IPV-PTSD severity and parenting stress, and positively correlated with medial prefrontal cortical (mPFC) activity in response to video-stimuli of stressful versus non-stressful mother–child interactions. Following a mental health assessment, 45 mothers and their children (ages 12–42 months) participated in a behavioral protocol involving free-play and laboratory stressors such as mother–child separation. Maternal DNA was extracted from saliva. Interactive behavior was rated on the CARE-Index. During subsequent fMRI scanning, mothers were shown films of free-play and separation drawn from this protocol. Maternal PTSD severity and parenting stress were negatively correlated with the mean percentage of methylation of NR3C1. Maternal mPFC activity in response to video-stimuli of mother–child separation versus play correlated positively to NR3C1 methylation, and negatively to maternal IPV-PTSD and parenting stress. Among interactive behavior variables, child cooperativeness in play was positively correlated with NR3C1 methylation. Thus, the present study is the first published report to our knowledge, suggesting convergence of behavioral, epigenetic, and neuroimaging data that form a psychobiological signature of parenting-risk in the context of early life stress and PTSD

  15. Monitoring polio supplementary immunization activities using an automated short text messaging system in Karachi, Pakistan

    PubMed Central

    Murtaza, A; Khoja, S; Zaidi, AK; Ali, SA

    2014-01-01

    Abstract Problem Polio remains endemic in many areas of Pakistan, including large urban centres such as Karachi. Approach During each of seven supplementary immunization activities against polio in Karachi, mobile phone numbers of the caregivers of a random sample of eligible children were obtained. A computer-based system was developed to send two questions – as short message service (SMS) texts – automatically to each number after the immunization activity: “Did the vaccinator visit your house?” and “Did the enrolled child in your household receive oral polio vaccine?” Persistent non-responders were phoned directly by an investigator. Local setting A cluster sampling technique was used to select representative samples of the caregivers of young children in Karachi in general and of such caregivers in three of the six “high-risk” districts of the city where polio cases were detected in 2011. Relevant changes In most of the supplementary immunization activities investigated, vaccine coverages estimated using the SMS system were very similar to those estimated by interviewing by phone those caregivers who never responded to the SMS messages. In the high-risk districts investigated, coverages estimated using the SMS system were also similar to those recorded – using lot quality assurance sampling – by the World Health Organization. Lessons learnt For the monitoring of coverage in supplementary immunization activities, automated SMS-based systems appear to be an attractive and relatively inexpensive option. Further research is needed to determine if coverage data collected by SMS-based systems provide estimates that are sufficiently accurate. Such systems may be useful in other large-scale immunization campaigns. PMID:24700982

  16. Human immunodeficiency virus-like particles activate multiple types of immune cells

    SciTech Connect

    Sailaja, Gangadhara; Skountzou, Ioanna; Quan, Fu-Shi; Compans, Richard W. . E-mail: compans@microbio.emory.edu; Kang, Sang-Moo . E-mail: skang2@emory.edu

    2007-06-05

    The rapid spread of human immunodeficiency virus (HIV) worldwide makes it a high priority to develop an effective vaccine. Since live attenuated or inactivated HIV is not likely to be approved as a vaccine due to safety concerns, HIV virus like particles (VLPs) offer an attractive alternative because they are safe due to the lack of a viral genome. Although HIV VLPs have been shown to induce humoral and cellular immune responses, it is important to understand the mechanisms by which they induce such responses and to improve their immunogenicity. We generated HIV VLPs, and VLPs containing Flt3 ligand (FL), a dendritic cell growth factor, to target VLPs to dendritic cells, and investigated the roles of these VLPs in the initiation of adaptive immune responses in vitro and in vivo. We found that HIV-1 VLPs induced maturation of dendritic cells and monocyte/macrophage populations in vitro and in vivo, with enhanced expression of maturation markers and cytokines. Dendritic cells pulsed with VLPs induced activation of splenocytes resulting in increased production of cytokines. VLPs containing FL were found to increase dendritic cells and monocyte/macrophage populations in the spleen when administered to mice. Administration of VLPs induced acute activation of multiple types of cells including T and B cells as indicated by enhanced expression of the early activation marker CD69 and down-regulation of the homing receptor CD62L. VLPs containing FL were an effective form of antigen in activating immune cells via dendritic cells, and immunization with HIV VLPs containing FL resulted in enhanced T helper type 2-like immune responses.

  17. Nature of "memory" in T-cell mediated antibacterial immunity: cellular parameters that distinguish between the active immune response and a state of "memory".

    PubMed Central

    North, R J; Deissler, J F

    1975-01-01

    Immunizing infection in mice with Listeria monocytogenes resulted in the generation of two distinct states of immunological reactivity. There was generated (i) a short-lived state of active immunity that functioned to urgently eliminate the infection organism from the tissues and (ii) a long-lives state of increased immunological potential that enabled the host to respond to seconday infection in an accelerated manner. Short-lived active immunity was mediated by replicating T cells and expressed by activated macrophages, and it ended when these cell types disappeared from the tissue soon after complete elimination of the parasite. Long-lived immunological protential was associated with a persistent level of delayed sensitivity and with the presence of a small number of nonreplicating protective T cells. It is suggested that the state of delayed sensitivity represents a state of immunological T-cell memory of the cell-mediated type. PMID:811559

  18. Maternal Hypoxia Increases the Activity of MMPs and Decreases the Expression of TIMPs in the Brain of Neonatal Rats

    PubMed Central

    Tong, Wenni; Chen, Wanqiu; Ostrowski, Robert P.; Ma, Qingyi; Souvenir, Rhonda; Zhang, Lubo; Zhang, John H.; Tang, Jiping

    2010-01-01

    A recent study has shown that increased activity of matrix metalloproteinases-2 and metalloproteinases-9 (MMP-2 and MMP-9) has detrimental effect on the brain after neonatal hypoxia. The present study determined the effect of maternal hypoxia on neuronal survivability and the activity of MMP-2 and MMP-9, as well as the expression of tissue inhibitors of metalloproteinase 1 and 2 (TIMP-1 and TIMP-2) in the brain of neonatal rats. Pregnant rats were exposed to 10.5% oxygen for 6 days from the gestation day 15 to day 21. Pups were sacrificed at day 0, 4, 7, 14, and 21 after birth. Body weight and brain weight of the pups were measured at each time point. The activity of MMP-2 and MMP-9 and the protein abundance of TIMP-1 and TIMP-2 were determined by zymography and Western blotting, respectively. The tissue distribution of MMPs was examined by immunofluorescence staining. The neuronal death was detected by Nissl staining. Maternal hypoxia caused significant decreases in body and brain size, increased activity of MMP-2 at day 0, and increased MMP-9 at day 0 and 4. The increased activity of the MMPs was accompanied by an overall tendency towards a reduced expression of TIMPs at all ages with the significance observed for TIMPs at day 0, 4, and 7. Immunofluorescence analysis showed an increased expression of MMP-2, MMP-9 in the hippocampus at day 0 and 4. Nissl staining revealed significant cell death in the hippocampus at day 0, 4, and 7. Functional tests showed worse neurobehavioral outcomes in the hypoxic animals. PMID:20017119

  19. Maternal Inheritance of Twist and Analysis of MAPK Activation in Embryos of the Polychaete Annelid Platynereis dumerilii

    PubMed Central

    Pfeifer, Kathrin; Schaub, Christoph; Domsch, Katrin; Dorresteijn, Adriaan; Wolfstetter, Georg

    2014-01-01

    In this study, we aimed to identify molecular mechanisms involved in the specification of the 4d (mesentoblast) lineage in Platynereis dumerilii. We employ RT-PCR and in situ hybridization against the Platynereis dumerilii twist homolog (Pdu-twist) to reveal mesodermal specification within this lineage. We show that Pdu-twist mRNA is already maternally distributed. After fertilization, ooplasmatic segregation leads to relocation of Pdu-twist transcripts into the somatoblast (2d) lineage and 4d, indicating that the maternal component of Pdu-twist might be an important prerequisite for further mesoderm specification but does not represent a defining characteristic of the mesentoblast. However, after the primordial germ cells have separated from the 4d lineage, zygotic transcription of Pdu-twist is exclusively observed in the myogenic progenitors, suggesting that mesodermal specification occurs after the 4d stage. Previous studies on spiral cleaving embryos revealed a spatio-temporal correlation between the 4d lineage and the activity of an embryonic organizer that is capable to induce the developmental fates of certain micromeres. This has raised the question if specification of the 4d lineage could be connected to the organizer activity. Therefore, we aimed to reveal the existence of such a proposed conserved organizer in Platynereis employing antibody staining against dpERK. In contrast to former observations in other spiralian embryos, activation of MAPK signaling during 2d and 4d formation cannot be detected which questions the existence of a conserved connection between organizer function and specification of the 4d lineage. However, our experiments unveil robust MAPK activation in the prospective nephroblasts as well as in the macromeres and some micromeres at the blastopore in gastrulating embryos. Inhibition of MAPK activation leads to larvae with a shortened body axis, defects in trunk muscle spreading and improper nervous system condensation, indicating a

  20. Soluble Immune Mediators and Vaginal Bacteria Impact Innate Genital Mucosal Antimicrobial Activity in Young Women

    PubMed Central

    Madan, Rebecca Pellett; Dezzutti, Charlene S.; Rabe, Lorna; Hillier, Sharon L.; Marrazzo, Jeanne; McGowan, Ian; Richardson, Barbra A.; Herold, Betsy C.

    2015-01-01

    Introduction Innate activity against Escherichia coli in female genital secretions may represent contributions from vaginal bacteria and host soluble immune mediators. We analyzed the relationship between E. coli inhibitory activity, soluble immune mediators, and vaginal bacteria in participants in MTN-004, a placebo-controlled trial of VivaGel®, a candidate product for topical HIV pre-exposure prophylaxis. Methods Escherichia coli inhibitory activity was quantified by colony reduction assay. Endocervical concentrations of interleukin (IL)-1β, IL-6, IL-12p40, macrophage inflammatory protein (MIP)-1α, granulocyte– macrophage colony-stimulating factor (GM-CSF), lactoferrin, and secretory leukocyte protease inhibitor (SLPI) were quantified to generate a cumulative mediator score. Vaginal bacteria were characterized by quantitative cultures. Results In the two placebo arms, higher soluble immune mediator score was associated with greater E. coli inhibitory activity (β = 17.49, 95% CI [12.77, 22.21] and β = 13.28, 95% CI [4.76, 21.80]). However, in the VivaGel arm, higher concentrations of E. coli (β = −3.80, 95% CI [−6.36, −1.25]) and group B Streptococcus (β = −3.91, 95% CI [−6.21, −1.60]) were associated with reduced E. coli inhibitory activity. Conclusions Both host mediators and vaginal bacteria impact E. coli inhibition in genital secretions. The relative contributions of host mediators and bacteria varied between women who used VivaGel vs placebos. PMID:26118476

  1. In vitro assessment of agave fructans (Agave salmiana) as prebiotics and immune system activators.

    PubMed

    Moreno-Vilet, L; Garcia-Hernandez, M H; Delgado-Portales, R E; Corral-Fernandez, N E; Cortez-Espinosa, N; Ruiz-Cabrera, M A; Portales-Perez, D P

    2014-02-01

    The prebiotic effect of agave fructans (Agave salmiana) was evaluated through the growth of two lactic acid bacterial (LAB) strains (Lactobacillus casei and Bifidobacterium lactis). The immune system was activated through the stimulation of peripheral blood mononuclear cells (PBMC) of healthy subjects testing fructans, LAB or a mixture of these compounds at different concentrations. Immune responses, such as early cell activation (CD69), cell cycle progression, nitric oxide (NO) production and the expression of transcription factors for lymphocyte differentiation, were analyzed. Compared with other fructans, the extracted agave fructans showed the highest prebiotic activity and increased levels of CD69 expression, proliferative activity and NO production when administered with the probiotic L. casei. The Th1 lymphocyte differentiation produced through LAB stimulation was greatly diminished after the incorporation of agave fructans. In conclusion, these types of fructans (A. salmiana) are involved in the activation and selective differentiation of cells of the immune system through interactions with probiotics. Thus, agave fructans represent a novel immunomodulator that might benefit the functional food industry. PMID:24211431

  2. Immune signaling pathways activated in response to different pathogenic micro-organisms in Bombyx mori.

    PubMed

    Liu, Wei; Liu, Jiabin; Lu, Yahong; Gong, Yongchang; Zhu, Min; Chen, Fei; Liang, Zi; Zhu, Liyuan; Kuang, Sulan; Hu, Xiaolong; Cao, Guangli; Xue, Renyu; Gong, Chengliang

    2015-06-01

    The JAK/STAT, Toll, Imd, and RNAi pathways are the major signaling pathways associated with insect innate immunity. To explore the different immune signaling pathways triggered in response to pathogenic micro-organism infections in the silkworm, Bombyx mori, the expression levels of the signal transducer and activator of transcription (BmSTAT), spatzle-1 (Bmspz-1), peptidoglycan-recognition protein LB (BmPGRP-LB), peptidoglycan-recognition protein LE (BmPGRP-LE), argonaute 2 (Bmago2), and dicer-2 (Bmdcr2) genes after challenge with Escherichia coli (E. coli), Serratiamarcescens (Sm), Bacillus bombyseptieus (Bab), Beauveriabassiana (Beb), nucleopolyhedrovirus (BmNPV), cypovirus (BmCPV), bidensovirus (BmBDV), or Nosemabombycis (Nb) were determined using real-time PCR. We found that the JAK/STAT pathway could be activated by challenge with BmNPV and BmBDV, the Toll pathway could be most robustly induced by challenge with Beb, the Imd pathway was mainly activated in response to infection by E. coli and Sm, and the RNAi pathway was not activated by viral infection, but could be triggered by some bacterial infections. These findings yield insights into the immune signaling pathways activated in response to different pathogenic micro-organisms in the silkworm.

  3. In vitro assessment of agave fructans (Agave salmiana) as prebiotics and immune system activators.

    PubMed

    Moreno-Vilet, L; Garcia-Hernandez, M H; Delgado-Portales, R E; Corral-Fernandez, N E; Cortez-Espinosa, N; Ruiz-Cabrera, M A; Portales-Perez, D P

    2014-02-01

    The prebiotic effect of agave fructans (Agave salmiana) was evaluated through the growth of two lactic acid bacterial (LAB) strains (Lactobacillus casei and Bifidobacterium lactis). The immune system was activated through the stimulation of peripheral blood mononuclear cells (PBMC) of healthy subjects testing fructans, LAB or a mixture of these compounds at different concentrations. Immune responses, such as early cell activation (CD69), cell cycle progression, nitric oxide (NO) production and the expression of transcription factors for lymphocyte differentiation, were analyzed. Compared with other fructans, the extracted agave fructans showed the highest prebiotic activity and increased levels of CD69 expression, proliferative activity and NO production when administered with the probiotic L. casei. The Th1 lymphocyte differentiation produced through LAB stimulation was greatly diminished after the incorporation of agave fructans. In conclusion, these types of fructans (A. salmiana) are involved in the activation and selective differentiation of cells of the immune system through interactions with probiotics. Thus, agave fructans represent a novel immunomodulator that might benefit the functional food industry.

  4. Imitating a stress response: a new hypothesis about the innate immune system's role in pregnancy.

    PubMed

    Schminkey, Donna L; Groer, Maureen

    2014-06-01

    Recent research challenges long-held hypotheses about mechanisms through which pregnancy induces maternal immune suppression or tolerance of the embryo/fetus. It is now understood that normal pregnancy engages the immune system and that the immune milieu changes with advancing gestation. We suggest that pregnancy mimics the innate immune system's response to stress, causing a sterile inflammatory response that is necessary for successful reproduction. The relationship between external stressors and immunomodulation in pregnancy has been acknowledged, but the specific mechanisms are still being explicated. Implantation and the first trimester are times of immune activation and intensive inflammation in the uterine environment. A period of immune quiescence during the second trimester allows for the growth and development of the maturing fetus. Labor is also an inflammatory event. The length of gestation and timing of parturition can be influenced by environmental stressors. These stressors affect pregnancy through neuroendocrine interaction with the immune system, specifically through the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-ovarian axis. Trophoblastic cells that constitute the maternal-fetal interface appear to harness the maternal immune system to promote and maximize the reproductive success of the mother and fetus. Pregnancy is a time of upregulated innate immune responses and decreased adaptive, cell-mediated responses. The inflammatory processes of pregnancy resemble an immune response to brief naturalistic stressors: there is a shift from T helper (Th) 1 to T helper (Th) 2 dominant adaptive immunity with a concomitant shift in cytokine production, decreased proliferation of T cells, and decreased cytotoxicity of natural killer (NK) cells. Inclusion of both murine and human studies, allows an exploration of insights into how trophoblasts influence the activity of the maternal innate immune system during gestation.

  5. Altered metabolism of gut microbiota contributes to chronic immune activation in HIV-infected individuals.

    PubMed

    Vázquez-Castellanos, J F; Serrano-Villar, S; Latorre, A; Artacho, A; Ferrús, M L; Madrid, N; Vallejo, A; Sainz, T; Martínez-Botas, J; Ferrando-Martínez, S; Vera, M; Dronda, F; Leal, M; Del Romero, J; Moreno, S; Estrada, V; Gosalbes, M J; Moya, A

    2015-07-01

    Altered interplay between gut mucosa and microbiota during treated HIV infection may possibly contribute to increased bacterial translocation and chronic immune activation, both of which are predictors of morbidity and mortality. Although a dysbiotic gut microbiota has recently been reported in HIV+ individuals, the metagenome gene pool associated with HIV infection remains unknown. The aim of this study is to characterize the functional gene content of gut microbiota in HIV+ patients and to define the metabolic pathways of this bacterial community, which is potentially associated with immune dysfunction. We determined systemic markers of innate and adaptive immunity in a cohort of HIV-infected individuals on successful antiretroviral therapy without comorbidities and in healthy non-HIV-infected subjects. Metagenome sequencing revealed an altered functional profile, with enrichment of the genes involved in various pathogenic processes, lipopolysaccharide biosynthesis, bacterial translocation, and other inflammatory pathways. In contrast, we observed depletion of genes involved in amino acid metabolism and energy processes. Bayesian networks showed significant interactions between the bacterial community, their altered metabolic pathways, and systemic markers of immune dysfunction. This study reveals altered metabolic activity of microbiota and provides novel insight into the potential host-microbiota interactions driving the sustained inflammatory state in successfully treated HIV-infected patients. PMID:25407519

  6. Parasitic and immune modulation of flight activity in honey bees tracked with optical counters.

    PubMed

    Alaux, Cédric; Crauser, Didier; Pioz, Maryline; Saulnier, Cyril; Le Conte, Yves

    2014-10-01

    Host-parasite interactions are often characterized by changes in the host behaviour, which are beneficial to either the parasite or the host, or are a non-adaptive byproduct of parasitism. These interactions are further complicated in animal society because individual fitness is associated with group performance. However, a better understanding of host-parasite interaction in animal society first requires the identification of individual host behavioural modification. Therefore, we challenged honey bee (Apis mellifera) workers with the parasite Nosema ceranae or an immune stimulation and tracked their flight activity over their lifetime with an optic counter. We found that bees responded differently to each stress: both Nosema-infected and immune-challenged bees performed a lower number of daily flights compared with control bees, but the duration of their flights increased and decreased over time, respectively. Overall, parasitized bees spent more time in the field each day than control bees, and the inverse was true for immune-challenged bees. Despite the stress of immune challenge, bees had a survival similar to that of control bees likely because of their restricted activity. We discuss how those different behavioural modifications could be adaptive phenotypes. This study provides new insights into how biological stress can affect the behaviour of individuals living in society and how host responses have evolved.

  7. Radiotherapy combined with TLR7/8 activation induces strong immune responses against gastrointestinal tumors.

    PubMed

    Schölch, Sebastian; Rauber, Conrad; Tietz, Alexandra; Rahbari, Nuh N; Bork, Ulrich; Schmidt, Thomas; Kahlert, Christoph; Haberkorn, Uwe; Tomai, Mark A; Lipson, Kenneth E; Carretero, Rafael; Weitz, Jürgen; Koch, Moritz; Huber, Peter E

    2015-03-10

    In addition to local cytotoxic activity, radiotherapy may also elicit local and systemic antitumor immunity, which may be augmented by immunotherapeutic agents including Toll-like receptor (TLR) 7/8 agonists. Here, we investigated the ability of 3M-011 (854A), a TLR7/8 agonist, to boost the antigen-presenting activity of dendritic cells (DC) as an adjuvant to radiotherapy. The combined treatment induced marked local and systemic responses in subcutaneous and orthotopic mouse models of colorectal and pancreatic cancer. In vitro cytotoxicity assays as well as in vivo depletion experiments with monoclonal antibodies identified NK and CD8 T cells as the cell populations mediating the cytotoxic effects of the treatment, while in vivo depletion of CD11c+ dendritic cells (DC) in CD11c-DTR transgenic mice revealed DC as the pivotal immune hub in this setting. The specificity of the immune reaction was confirmed by ELISPOT assays. TLR7/8 agonists therefore seem to be potent adjuvants to radiotherapy, inducing strong local and profound systemic immune responses to tumor antigens released by conventional therapy.

  8. Radiotherapy combined with TLR7/8 activation induces strong immune responses against gastrointestinal tumors

    PubMed Central

    Tietz, Alexandra; Rahbari, Nuh N.; Bork, Ulrich; Schmidt, Thomas; Kahlert, Christoph; Haberkorn, Uwe; Tomai, Mark A.; Lipson, Kenneth E.; Carretero, Rafael; Weitz, Jürgen; Koch, Moritz; Huber, Peter E.

    2015-01-01

    In addition to local cytotoxic activity, radiotherapy may also elicit local and systemic antitumor immunity, which may be augmented by immunotherapeutic agents including Toll-like receptor (TLR) 7/8 agonists. Here, we investigated the ability of 3M-011 (854A), a TLR7/8 agonist, to boost the antigen-presenting activity of dendritic cells (DC) as an adjuvant to radiotherapy. The combined treatment induced marked local and systemic responses in subcutaneous and orthotopic mouse models of colorectal and pancreatic cancer. In vitro cytotoxicity assays as well as in vivo depletion experiments with monoclonal antibodies identified NK and CD8 T cells as the cell populations mediating the cytotoxic effects of the treatment, while in vivo depletion of CD11c+ dendritic cells (DC) in CD11c-DTR transgenic mice revealed DC as the pivotal immune hub in this setting. The specificity of the immune reaction was confirmed by ELISPOT assays. TLR7/8 agonists therefore seem to be potent adjuvants to radiotherapy, inducing strong local and profound systemic immune responses to tumor antigens released by conventional therapy. PMID:25609199

  9. Sex effects on neurodevelopmental outcomes of innate immune activation during prenatal and neonatal life

    PubMed Central

    Rana, Shadna A.; Aavani, Tooka; Pittman, Quentin J.

    2012-01-01

    Humans are exposed to potentially harmful agents (bacteria, viruses, toxins) throughout our lifespan; the consequences of such exposure can alter central nervous system development. Exposure to immunogens during pregnancy increases the risk of developing neurological disorders such as schizophrenia and autism. Further, sex hormones, such as estrogen, have strong modulatory effects on immune function and have also been implicated in the development of neuropathologies (e.g., schizophrenia and depression). Similarly, animal studies have demonstrated that immunogen exposure in utero or during the neonatal period, at a time when the brain is undergoing maturation, can induce changes in learning and memory, as well as dopamine-mediated behaviors in a sex-specific manner. Literature that covers the effects of immunogens on innate immune activation and ultimately the development of the adult brain and behavior is riddled with contradictory findings, and the addition of sex as a factor only adds to the complexity. This review provides evidence that innate immune activation during critical periods of development may have effects on the adult brain in a sex-specific manner. Issues regarding sex bias in research as well as variability in animal models of immune function are discussed. PMID:22516179