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.
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Acknowledgements
We acknowledge Richard DiPaolo and Thanh-Long Nguyen for sharing their knowledge of murine flow cytometry and thank Somashubra Bhattacharya for expert technical assistance. We appreciate Noah Hillman’s critical review of our manuscript. This work was presented in part at the 2012 (Boston, MA) and 2013 (Washington, DC) annual Pediatric Academic Societies meetings.
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Gleditsch, D., Shornick, L., Van Steenwinckel, J. et al. Maternal inflammation modulates infant immune response patterns to viral lung challenge in a murine model. Pediatr Res 76, 33–40 (2014). https://doi.org/10.1038/pr.2014.57
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DOI: https://doi.org/10.1038/pr.2014.57
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