Murine chorioamnionitis is associated with decreased mortality during neonatal bacterial sepsis 4635

Description Chorioamnionitis (CA) is infection and/or inflammation of the fetal membranes and the placenta, and is a common complication during pregnancy. CA is an independent risk factor for many immune-mediated morbidities, including neonatal sepsis, but the effects of CA on offspring immune responses are incompletely understood. Our lab previously demonstrated that a murine model of sterile CA (IP LPS during gestation) was associated with hyporesponsive macrophage antibacterial responses ex vivo. To study CA-induced offspring effects in vivo, we employed our model of sterile CA at E17.5 and IP infected P4-5 offspring with 5x102 CFU E. coli or 1x108 CFU S. epidermidis. Pups were monitored for survival and splenic macrophages underwent immunophenotyping by flow cytometry 12 hours post infection. CA-exposed offspring had a survival advantage during both S. epidermidis and E. coli sepsis (S. epi: PBS 44% vs CA 100% survival p < 0.05, E. coli: PBS 40% vs CA 71% survival p < 0.1). Bacterial burden was similar between groups but CA-exposed macrophages had decreased CD86 expression after E. coli infection. CD86 has been proposed as an early biomarker for neonatal sepsis and CD86 deletion is associated with improved sepsis survival in adult models of disease. CA-induced CD86 downregulation could be playing a similar beneficial role during neonatal sepsis, but further studies are needed to understand the relationship between perinatal inflammation, CD86 expression, and neonatal sepsis outcomes. Funding Sources Supported by T32GM139776; T32AI007485; R01AI141673 Topic Categories Mucosal and Regional Immunology (MUC)