title: M cells expressing the complement C5a receptor are efficient targets for mucosal vaccine delivery.
abstract: 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.
authors: Department of Molecular Biology and Institute for Molecular Biology and Genetics, Chonbuk National University, Jeonju, Korea.
authors: Sae-Hae
authors: SH
authors: Kim
authors: Dae-Im
authors: DI
authors: Jung
authors: In-Young
authors: IY
authors: Yang
authors: Ju
authors: J
authors: Kim
authors: Kyung-Yeol
authors: KY
authors: Lee
authors: Tomonori
authors: T
authors: Nochi
authors: Hiroshi
authors: H
authors: Kiyono
authors: Yong-Suk
authors: YS
authors: Jang
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology; D015153:Blotting, Western; D018938:Caco-2 Cells; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D060888:Real-Time Polymerase Chain Reaction; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000276:immunology* / Q000378:metabolism; D014612:Vaccines / Q000008:administration & dosage*
chemical_list: D000942:Antigens, Bacterial; C488033:C5AR1 protein, human; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D014612:Vaccines