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Murine chorioamnionitis causes a dampened innate immune response that persists into infancy
Abstract   Peer reviewed

Murine chorioamnionitis causes a dampened innate immune response that persists into infancy

Jessica Knobbe and Jennifer Bermick
The Journal of immunology (1950), Vol.210(1_Supplement), pp.70-70.09
05/01/2023
DOI: 10.4049/jimmunol.210.Supp.70.09

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Abstract

Abstract Chorioamnionitis is infection or inflammation of the chorion, the amnion, and the placenta. Chorioamnionitis is associated with 40–70% of preterm births and increases the risk of many immune-mediated neonatal sequelae. Chorioamnionitis also increases the risk of developing wheezing and asthma later in life. With this in mind, we sought to characterize the innate immune dysfunction associated with chorioamnionitis. We hypothesized that neonatal and infant mice exposed to chorioamnionitis would display dampened innate immune responses to bacterial pathogens. To test this, genetically homogenous C57Bl/6 dams were injected IP with LPS or PBS on E18.5. Pups were born naturally and euthanized at P4–6 (neonate) or P12–14 (infant). Splenic F4/80+ cells were isolated, then unstimulated or stimulated with heat-killed Staph epidermidis, Staph aureus, or Escherichia colifor 24 hours. IL-1β, IL-6, IL-10, IL-12, KC, MCP-1, MIP-1α, and TNF-α were quantified in cell supernatants. We observed that E. coli-stimulated F4/80+ cells from chorioamnionitis-exposed infant mice displayed lower concentrations of IL-6 (p<0.0001) and MCP-1 (p=.0057) compared to controls. S. epidermidis-stimulated F4/80+ cells from chorioamnionitis-exposed infant mice also displayed lower concentrations of MCP-1 (p=.0024) compared to controls. This suggests that murine chorioamnionitis impacts the developing immune system, resulting in a dampened innate immune response to bacterial pathogens that persists into infancy. Supported by grants from the NIH (T32GM139776, R01AI141673).

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