PMID- 19907495 OWN - NLM STAT- MEDLINE DCOM- 20100105 LR - 20220316 IS - 1476-4687 (Electronic) IS - 0028-0836 (Linking) VI - 462 IP - 7270 DP - 2009 Nov 12 TI - Uptake through glycoprotein 2 of FimH(+) bacteria by M cells initiates mucosal immune response. PG - 226-30 LID - 10.1038/nature08529 [doi] AB - 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 Peyer's 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 Peyer's 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. FAU - Hase, Koji AU - Hase K AD - Laboratory for Epithelial Immunobiology, Research Center for Allergy and Immunology, RIKEN, Kanagawa 230-0045, Japan. FAU - Kawano, Kazuya AU - Kawano K FAU - Nochi, Tomonori AU - Nochi T FAU - Pontes, Gemilson Soares AU - Pontes GS FAU - Fukuda, Shinji AU - Fukuda S FAU - Ebisawa, Masashi AU - Ebisawa M FAU - Kadokura, Kazunori AU - Kadokura K FAU - Tobe, Toru AU - Tobe T FAU - Fujimura, Yumiko AU - Fujimura Y FAU - Kawano, Sayaka AU - Kawano S FAU - Yabashi, Atsuko AU - Yabashi A FAU - Waguri, Satoshi AU - Waguri S FAU - Nakato, Gaku AU - Nakato G FAU - Kimura, Shunsuke AU - Kimura S FAU - Murakami, Takaya AU - Murakami T FAU - Iimura, Mitsutoshi AU - Iimura M FAU - Hamura, Kimiyo AU - Hamura K FAU - Fukuoka, Shin-Ichi AU - Fukuoka S FAU - Lowe, Anson W AU - Lowe AW FAU - Itoh, Kikuji AU - Itoh K FAU - Kiyono, Hiroshi AU - Kiyono H FAU - Ohno, Hiroshi AU - Ohno H LA - eng GR - DK43294/DK/NIDDK NIH HHS/United States GR - DK56339/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - England TA - Nature JT - Nature JID - 0410462 RN - 0 (Adhesins, Escherichia coli) RN - 0 (Antigens, Bacterial) RN - 0 (GP2 protein, human) RN - 0 (GPI-Linked Proteins) RN - 0 (Glycoproteins) RN - 0 (Gp2 protein, mouse) RN - 0 (Membrane Glycoproteins) RN - 0 (fimH protein, E coli) RN - 147680-16-8 (Fimbriae Proteins) SB - IM CIN - Future Microbiol. 2010 Apr;5(4):549-53. PMID: 20353296 MH - Adhesins, Escherichia coli/genetics/immunology/*metabolism MH - Animals MH - Antigens, Bacterial/genetics/immunology/*metabolism MH - Cell Line MH - Epithelial Cells/*immunology/metabolism MH - Escherichia coli/immunology/metabolism MH - Fimbriae Proteins/genetics/immunology/*metabolism MH - GPI-Linked Proteins MH - Glycoproteins MH - HeLa Cells MH - Humans MH - Immunity, Mucosal/*immunology MH - Intestines/cytology MH - Membrane Glycoproteins/*metabolism MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Peyer's Patches/*cytology/immunology MH - Salmonella typhimurium/genetics/immunology/metabolism MH - Substrate Specificity EDAT- 2009/11/13 06:00 MHDA- 2010/01/06 06:00 CRDT- 2009/11/13 06:00 PHST- 2009/08/16 00:00 [received] PHST- 2009/09/23 00:00 [accepted] PHST- 2009/11/13 06:00 [entrez] PHST- 2009/11/13 06:00 [pubmed] PHST- 2010/01/06 06:00 [medline] AID - nature08529 [pii] AID - 10.1038/nature08529 [doi] PST - ppublish SO - Nature. 2009 Nov 12;462(7270):226-30. doi: 10.1038/nature08529.