Complement C5a promotes antigen cross-presentation by Peyer's patch monocyte-derived dendritic cells and drives a protective CD8+ T cell response

Abstract

The complement fragment C5a is closely associated with adaptive immune induction in the mucosa. However, the mechanisms that control CD8⁺ T cell responses by C5a have not been extensively explored. This study reveals that C5/C5a in the Peyer's patch (PP) subepithelial dome increases upon oral Listeria infection. We hypothesize that C5aR⁺ PP cells play an important role in the induction of antigen-specific T cell immunity. Using single-cell RNA sequencing, we identify C5aR- and lysozyme-expressing dendritic cells (C5aR⁺ LysoDCs) in PP and examine their role in CD8⁺ T cell immune induction. Stimulation of C5aR⁺ LysoDCs by C5a increases reactive oxygen species levels, leading to efficient antigen cross-presentation, which elicits an antigen-specific CD8⁺ T cell response. In C5-deficient mice, oral co-administration of C5a and Listeria enhances Listeria-specific cytotoxic T cell levels. Collectively, these findings suggest a role of the complement system in intestinal T cell immunity.

Keywords: C5a receptor; CD8(+) T cell; Peyer’s patch; complement C5a; cross-presentation; dendritic cells.