Peyer's patches are required for Bacteroides fragilis to induce protective systemic IgA

Gut-educated IgA-secreting plasma cells that disseminate beyond the mucosa and into systemic tissues can help prevent disease in several contexts. Here we show, the commensal bacteria Bacteroides fragilis (Bf), is an efficient inducer of systemic IgA responses. The generation of bone marrow IgA plasma cells and high levels of serum IgA specific to Bf requires robust intestinal colonization. Bf-specific IgA responses were severely diminished in mice lacking Peyer's patches, but not mice lacking a cecal patch. Colonization resulted in few changes in the host transcriptional profile in the gut, suggesting a commensal relationship. High levels of Bf-specific serum IgA, but not IgG, provided protection from peritoneal abscess formation in a bowel perforation model of Bf dissemination. These findings demonstrate a critical role for bacterial colonization and Peyer's patches in the induction of robust systemic IgA responses that confer protection from bacterial dissemination originating from the gut. Overall design: Mice were treated with B. fragilis by oral gavage and given either 1 or 6 doses and then euthanized 2 or 4 weeks after treatment. A 2cm piece of colon or small intestine were washed to remove feces and then RNA was isolated for RNAseq analysis.