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

Kouji 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

Research output: Contribution to journalArticle

333 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)226-230
Number of pages5
JournalNature
Volume462
Issue number7270
DOIs
Publication statusPublished - 2009 Nov 12
Externally publishedYes

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Mucosal Immunity
Glycoproteins
Bacteria
Transcytosis
Peyer's Patches
Histocompatibility Antigens Class II
Immune System
Bacterial Fimbriae
Cell Membrane
Cytoplasmic Vesicles
Antigens
Secretory Immunoglobulin A
Antigen Receptors
Salmonella enterica
Enterocytes
Enterobacteriaceae
Communicable Diseases
Vaccination
Vaccines
Epithelial Cells

ASJC Scopus subject areas

  • General

Cite this

Hase, K., Kawano, K., Nochi, T., Pontes, G. S., Fukuda, S., Ebisawa, M., ... Ohno, H. (2009). Uptake through glycoprotein 2 of FimH + bacteria by M cells initiates mucosal immune response. Nature, 462(7270), 226-230. https://doi.org/10.1038/nature08529

Uptake through glycoprotein 2 of FimH + bacteria by M cells initiates mucosal immune response. / Hase, Kouji; Kawano, Kazuya; Nochi, Tomonori; Pontes, Gemilson Soares; Fukuda, Shinji; Ebisawa, Masashi; Kadokura, Kazunori; Tobe, Toru; Fujimura, Yumiko; Kawano, Sayaka; Yabashi, Atsuko; Waguri, Satoshi; Nakato, Gaku; Kimura, Shunsuke; Murakami, Takaya; Iimura, Mitsutoshi; Hamura, Kimiyo; Fukuoka, Shin Ichi; Lowe, Anson W.; Itoh, Kikuji; Kiyono, Hiroshi; Ohno, Hiroshi.

In: Nature, Vol. 462, No. 7270, 12.11.2009, p. 226-230.

Research output: Contribution to journalArticle

Hase, K, Kawano, K, Nochi, T, Pontes, GS, Fukuda, S, Ebisawa, M, Kadokura, K, Tobe, T, Fujimura, Y, Kawano, S, Yabashi, A, Waguri, S, Nakato, G, Kimura, S, Murakami, T, Iimura, M, Hamura, K, Fukuoka, SI, Lowe, AW, Itoh, K, Kiyono, H & Ohno, H 2009, 'Uptake through glycoprotein 2 of FimH + bacteria by M cells initiates mucosal immune response', Nature, vol. 462, no. 7270, pp. 226-230. https://doi.org/10.1038/nature08529
Hase K, Kawano K, Nochi T, Pontes GS, Fukuda S, Ebisawa M et al. Uptake through glycoprotein 2 of FimH + bacteria by M cells initiates mucosal immune response. Nature. 2009 Nov 12;462(7270):226-230. https://doi.org/10.1038/nature08529
Hase, Kouji ; Kawano, Kazuya ; Nochi, Tomonori ; Pontes, Gemilson Soares ; Fukuda, Shinji ; Ebisawa, Masashi ; Kadokura, Kazunori ; Tobe, Toru ; Fujimura, Yumiko ; Kawano, Sayaka ; Yabashi, Atsuko ; Waguri, Satoshi ; Nakato, Gaku ; Kimura, Shunsuke ; Murakami, Takaya ; Iimura, Mitsutoshi ; Hamura, Kimiyo ; Fukuoka, Shin Ichi ; Lowe, Anson W. ; Itoh, Kikuji ; Kiyono, Hiroshi ; Ohno, Hiroshi. / Uptake through glycoprotein 2 of FimH + bacteria by M cells initiates mucosal immune response. In: Nature. 2009 ; Vol. 462, No. 7270. pp. 226-230.
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