Dorothy D Gleditsch1, Laurie P Shornick2, Juliette Van Steenwinckel3, Pierre Gressens4, Ryan P Weisert1, Joyce M Koenig5. 1. Department of Pediatrics, Saint Louis University, St Louis, Missouri. 2. 1] Department of Biology, Saint Louis University, St Louis, Missouri [2] Department of Molecular Microbiology & Immunology, Saint Louis University, St Louis, Missouri. 3. 1] Inserm, U1141, Paris, France [2] University of Paris Diderot, Sorbonne Paris Cité, UMRS 1141, Paris, France. 4. 1] Inserm, U1141, Paris, France [2] University of Paris Diderot, Sorbonne Paris Cité, UMRS 1141, Paris, France [3] Centre for the Developing Brain, Department of Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas' Hospital, London, UK. 5. 1] Department of Pediatrics, Saint Louis University, St Louis, Missouri [2] Department of Molecular Microbiology & Immunology, Saint Louis University, St Louis, Missouri.
Abstract
BACKGROUND: Chorioamnionitis, an inflammatory gestational disorder, commonly precedes preterm delivery. Preterm infants may be at particular risk for inflammation-related morbidity related to infection, although the pathogenic mechanisms are unclear. We hypothesized that maternal inflammation modulates immune programming to drive postnatal inflammatory processes. METHODS: We used a novel combined murine model to treat late gestation dams with low-dose lipopolysaccharide (LPS) and to secondarily challenge exposed neonates or weanlings with Sendai virus (SeV) lung infection. Multiple organs were analyzed to characterize age-specific postnatal immune and inflammatory responses. RESULTS: Maternal LPS treatment enhanced innate immune populations in the lungs, livers, and/or spleens of exposed neonates or weanlings. Secondary lung SeV infection variably affected neutrophil, macrophage, and dendritic cell proportions in multiple organs of exposed pups. Neonatal lung infection induced brain interleukin (IL)-4 expression, although this response was muted in LPS-exposed pups. Adaptive immune cells, including lung, lymph node, and thymic lymphocytes and lung CD4 cells expressing FoxP3, interferon (IFN)-γ, or IL-17, were variably prominent in LPS-exposed pups. CONCLUSION: Maternal inflammation modifies postnatal immunity and augments systemic inflammatory responses to viral lung infection in an age-specific manner. We speculate that inflammatory modulation of the developing immune system contributes to chronic morbidity and mortality in preterm infants.
BACKGROUND: Chorioamnionitis, an inflammatory gestational disorder, commonly precedes preterm delivery. Preterm infants may be at particular risk for inflammation-related morbidity related to infection, although the pathogenic mechanisms are unclear. We hypothesized that maternal inflammation modulates immune programming to drive postnatal inflammatory processes. METHODS: We used a novel combined murine model to treat late gestation dams with low-dose lipopolysaccharide (LPS) and to secondarily challenge exposed neonates or weanlings with Sendai virus (SeV) lung infection. Multiple organs were analyzed to characterize age-specific postnatal immune and inflammatory responses. RESULTS: Maternal LPS treatment enhanced innate immune populations in the lungs, livers, and/or spleens of exposed neonates or weanlings. Secondary lung SeV infection variably affected neutrophil, macrophage, and dendritic cell proportions in multiple organs of exposed pups. Neonatal lung infection induced brain interleukin (IL)-4 expression, although this response was muted in LPS-exposed pups. Adaptive immune cells, including lung, lymph node, and thymic lymphocytes and lung CD4 cells expressing FoxP3, interferon (IFN)-γ, or IL-17, were variably prominent in LPS-exposed pups. CONCLUSION:Maternal inflammation modifies postnatal immunity and augments systemic inflammatory responses to viral lung infection in an age-specific manner. We speculate that inflammatory modulation of the developing immune system contributes to chronic morbidity and mortality in preterm infants.