Age associated differential innate immune response to strains of Escherichia coli in neonatal sepsis model

Abstract Bloodstream infections, causing late-onset neonatal sepsis (LOS), have an incidence rate of 10% in very low birth weight (<1500 grams) infants. Despite the prevalence in neonates, the current understanding of bloodstream infections and the resulting immune response is predominately based on research in adults, which is often a complication of surgery. In contrast, sepsis in infants is often a result of the dissemination of bacteria from the gut. Additionally, observations have shown differences in the neonatal immune response, such as a decrease in gene expression associated with TLR signaling pathways, compared to adults. One question remaining in the field is the age dependent differences in pathogen detection by innate cells, including dendritic cells and macrophages. Use RAW-Blue reporter cells, and splenocytes cultured from mice at different ages, we have found disparate responses to gut-resident E. coli dependent on pathogen status of the bacteria. Specifically, we have observed differential increases in IL-6, TNFα, and IL-1β, along with NFκB activation that is dependent on live bacteria. Additionally, changes in this response were associated with age, suggesting differences in the innate immune response throughout early life. Future directions include measuring RNA expression of dendritic cells and macrophages between the age groups and exploring how the differences contribute to infection outcomes in a model of sepsis. Supported by grants from NIH (DK122187).