Gut microbial dysbiosis due to Helicobacter drives marginal zone B cell development in the absence of IL-10 signaling in macrophages (LYM7P.623)

Abstract

Abstract IL-10 plays an essential role in maintaining homeostasis in the gut in response to the microbiome. However, it is unknown whether IL-10 also facilitates immune homeostasis at distal sites. To address this, we asked whether splenic immune populations were altered in IL-10-deficient mice with differential susceptibility to microbiome-dependent spontaneous enterocolitis. Susceptible mice exhibited a significant increase in splenic macrophages, neutrophils and marginal zone (MZ) B cells that was inhibited by IL-10 signaling in macrophages, but not B cells. The increase in myeloid cells was due to increased proliferation that correlated with increased MZ B cell differentiation. Cohousing and antibiotic treatment suggested that the alteration in splenic immune homeostasis was microbiome-dependent. 16S rRNA sequencing reveled that susceptible mice harbored a more diverse microbiome with a significant increase in the abundance of the bacterial genus Helicobacter. The introduction of H. hepaticus to the gut of nonsusceptible mice was sufficient to drive myeloid cell expansion and MZ B cell development. Given that MZ B cells are part of the first line of defense against blood-borne-pathogens, their increase following a breach in the gut epithelial barrier would be protective. Thus IL-10 is an essential gatekeeper that maintains immune homeostasis at distal sites that can become functionally imbalanced upon the introduction of specific bacteria to the intestinal track.