Uptake through glycoprotein 2 of FimH + bacteria by M cells initiates mucosal immune response

Koji Hase, Kazuya Kawano, Tomonori Nochi, Gemilson Soares Pontes, Shinji Fukuda, Masashi Ebisawa, Kazunori Kadokura, Toru Tobe, Yumiko Fujimura, Sayaka Kawano, Atsuko Yabashi, Satoshi Waguri, Gaku Nakato, Shunsuke Kimura, Takaya Murakami, Mitsutoshi Iimura, Kimiyo Hamura, Shin Ichi Fukuoka, Anson W. Lowe, Kikuji ItohHiroshi Kiyono, Hiroshi Ohno

研究成果: Article査読

425 被引用数 (Scopus)

抄録

The mucosal immune system forms the largest part of the entire immune system, containing about three-quarters of all lymphocytes and producing grams of secretory IgA daily to protect the mucosal surface from pathogens. To evoke the mucosal immune response, antigens on the mucosal surface must be transported across the epithelial barrier into organized lymphoid structures such as Peyers patches. This function, called antigen transcytosis, is mediated by specialized epithelial M cells. The molecular mechanisms promoting this antigen uptake, however, are largely unknown. Here we report that glycoprotein 2 (GP2), specifically expressed on the apical plasma membrane of M cells among enterocytes, serves as a transcytotic receptor for mucosal antigens. Recombinant GP2 protein selectively bound a subset of commensal and pathogenic enterobacteria, including Escherichia coli and Salmonella enterica serovar Typhimurium (S. Typhimurium), by recognizing FimH, a component of type I pili on the bacterial outer membrane. Consistently, these bacteria were colocalized with endogenous GP2 on the apical plasma membrane as well as in cytoplasmic vesicles in M cells. Moreover, deficiency of bacterial FimH or host GP2 led to defects in transcytosis of type-I-piliated bacteria through M cells, resulting in an attenuation of antigen-specific immune responses in Peyers patches. GP2 is therefore a previously unrecognized transcytotic receptor on M cells for type-I-piliated bacteria and is a prerequisite for the mucosal immune response to these bacteria. Given that M cells are considered a promising target for oral vaccination against various infectious diseases, the GP2-dependent transcytotic pathway could provide a new target for the development of M-cell-targeted mucosal vaccines.

本文言語English
ページ(範囲)226-230
ページ数5
ジャーナルNature
462
7270
DOI
出版ステータスPublished - 2009 11 12
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ASJC Scopus subject areas

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