A33 EOSINOPHILS PROMOTE SALMONELLA TYPHIMURIUM COLONIZATION IN THE MURINE SMALL INTESTINE

TL;DR

Eosinophils in the small intestine help Salmonella bacteria grow more, rather than fighting them, in mice.

Contribution

This study is the first to show that eosinophils promote Salmonella colonization in the small intestine during infection.

Findings

Eosinophils in mesenteric lymph nodes increased in frequency after Salmonella infection.

Eosinophils in the small intestine showed increased MHCII expression during infection.

Mice without eosinophils had reduced Salmonella colonization in the ileum.

Abstract

During inflammatory bowel disease (IBD) both the number of intestinal eosinophils and susceptibility to enteric bacterial infections can drastically increase. It is unknown, however, whether eosinophils recruited to the tissues lining the gastrointestinal (GI) tract during severe disease help to control pathogenic bacterial colonization or whether their presence promotes bacterial infection. No studies to date have examined the role of eosinophils during an acute bacterial infection in the small intestine.

Our research aims to uncover the role of eosinophils during an enteric Salmonella infection in mice and we hypothesize that eosinophils undergo phenotypic changes in the presence of Salmonella and aid in the clearance of this enteric bacterial pathogen.

To assess how the presence of Salmonella impacts the frequency and phenotype of eosinophils we performed flow cytometry on eosinophils isolated from mice 3-days post-oral infection with Salmonella enterica serovar Typhimurium and compared these findings to naïve BALB/c controls. To determine if eosinophils are essential for controlling Salmonella infection we quantified levels of Salmonella colonization along the GI tract, liver and spleen of wild-type and eosinophil-deficient (ΔdblGATA) littermate mice by plating homogenized tissues on LB agar.

Following an oral Salmonella infection we found higher frequencies of eosinophils in the gut-draining mesenteric lymph nodes compared to uninfected mice. Intestinal lamina propria-resident eosinophils in the small intestine and colon displayed altered phenotypes following infection in an intestinal-region specific manner: during infection, in the small intestine eosinophils increased their expression of MHCII, and in the colon eosinophils displayed elevated granularity. When wild-type and ΔdblGATA mice were pre-treated with the antibiotic streptomycin 1-day prior to infection to confer robust Salmonella burdens in the small intestine we found a significant reduction in Salmonella colonization in the ileum of the small intestine in ΔdblGATA mice compared to their wild-type littermates. These data suggest eosinophils have a role in promoting colonization by this enteric bacterial pathogen.

Our data contribute to the growing evidence that microbes can influence the phenotype of intestinal eosinophils and demonstrate that the influence of and requirements for eosinophils during bacterial infection is highly context-dependent. We found that eosinophils are not essential for controlling an acute enteric Salmonella infection and instead they promote Salmonella colonization in the small intestine.

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