Bacteroides fragilis colonization induces protective systemic IgA.

Abstract

BACKGROUND: Gut-educated IgA-secreting plasma cells that disseminate beyond the mucosa and into systemic tissues can help prevent disease in several contexts. Many species of bacteria have been described as efficient inducers of mucosal IgA, including the commensal bacteria Bacteroides fragilis (Bf); however, less is known about inducers of systemic IgA responses. RESULTS: Here, we show that 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 and minimal extrafollicular stimulation. The high levels of Bf-specific serum IgA induced by colonization provided protection from peritoneal abscess formation in a bowel perforation model of Bf dissemination. CONCLUSION: These findings demonstrate a critical role for bacterial colonization and interaction with Peyer's patches for the induction of a robust systemic IgA response. The presence of high levels of serum IgA specific to Bf confers protection from bacterial dissemination and abscess formation in a model of bowel perforation. Video Abstract.