Maternal protection from bacterial translocation in a murine model of late-onset neonatal sepsis (LOS)

---

Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B215
Abstract ID: 5043

Presenting Author:
Christian R Tamar , Research Assistant at Mayo Clin. Grad. Sch. of Biomed. Sci.

Abstract:

Late-onset neonatal sepsis (LOS), resulting from a bloodstream infection at least 72 hours after birth, is a major contributor to neonatal mortality. In a substantial portion of LOS cases, the causative pathogen is present as a member of the intestinal microbial community before dissemination, implicating intestinal translocation as a source of bloodstream infections. One potential pathway of bacterial translocation is through goblet cell-associated antigen passages, or GAPs, in colonic goblet cells. The presence of luminal EGF, obtained from breastmilk, and subsequent EGF receptor (EGFR) signaling in the intestine inhibits the formation of GAPs. We have established that disruption of EGFR signaling in pups leads to dissemination of the enteric pathogen Escherichia coli to the mesenteric lymph node (MLN). As pathogen dissemination was quickly followed by mortality, we use this as a preclinical model of LOS. Further work with this model focuses on the role of milk-derived immunoglobulins in reducing pathogen colonization and protecting from disease resulting from intestinal translocation. Through cross-fostering litters between dams immunized against E. coli and unimmunized dams, along with a comparison in disease between litters from immunized wild-type mice and IgA-/- mice, we aim to describe the protective role of mammary IgA. These experiments will also provide further implications for the role of human milk and human milk factors in protection from LOS.