M cells expressing the complement C5a receptor are efficient targets for mucosal vaccine delivery

In the mucosal immune system, M cells are known as specialized epithelial cells that take up luminal antigens, although the receptors on M cells and the mechanism of antigen uptake into M cells are not well‐understood. Here, we report the expression of the complement C5a receptor (C5aR) on the apical surface of M cells. C5ar mRNA expression in co‐cultured Caco‐2 human M‐like cells was six‐fold higher than in mono‐cultured cells. C5aR expression was detected together with glycoprotein 2, an M‐cell‐specific protein, on the apical surface of M‐like cells and mouse Peyer's patch M cells. Interestingly, after oral administration of Yersinia enterocolitica which expresses outer membrane protein H (OmpH) that is homologous to the Skp α1 domain of Escherichia coli, a ligand of C5aR, dense clustering and phosphorylation of C5aR were detected in M cells. Finally, targeted antigen delivery to M cells using C5aR as a receptor was achieved using the OmpH α1 of Y. enterocolitica such that the induction of ligand‐conjugated antigen‐specific immune responses was confirmed in mice after oral immunization of the OmpH β1α1‐conjugated antigen. Collectively, we identified C5aR expression on M cells and suggest that C5aR could be used as a target receptor for mucosal antigen delivery.