Indigenous opportunistic bacteria inhabit mammalian gut-associated lymphoid tissues and share a mucosal antibody-mediated symbiosis

Takashi Obata, Yoshiyuki Goto, Jun Kunisaw, Shintaro Sato, Mitsuo Sakamoto, Hiromi Setoyama, Takahiro Matsuki, Kazuhiko Nonaka, Naoko Shibata, Masashi Gohda, Yuki Kagiyama, Tomonori Nochi, Yoshikazu Yuki, Yoshiko Fukuyama, Akira Mukai, Shinichiro Shinzaki, Kohtaro Fujihashi, Chihiro Sasakawa, Hideki Iijima, Masatoshi GotoYoshinori Umesaki, Yoshimi Benno, Hiroshi Kiyono

Research output: Contribution to journalArticlepeer-review

147 Citations (Scopus)

Abstract

The indigenous bacteria create natural cohabitation niches together with mucosal Abs in the gastrointestinal (GI) tract. Here we report that opportunistic bacteria, largely Alcaligenes species, specifically inhabit host Peyer's patches (PPs) and isolated lymphoid follicles, with the associated preferential induction of antigen-specific mucosal IgA Abs in the GI tract. Alcaligenes were identified as the dominant bacteria on the interior of PPs from naïve, specific-pathogen-free but not from germ-free mice. Oral transfer of intratissue uncultured Alcaligenes into germ-free mice resulted in the presence of Alcaligenes inside the PPs of recipients. This result was further supported by the induction of antigen-specific Ab-producing cells in the mucosal (e.g., PPs) but not systemic compartment (e.g., spleen). The preferential presence of Alcaligenes inside PPs and the associated induction of intestinal secretory IgA Abs were also observed in both monkeys and humans. Localized mucosal Ab-mediated symbiotic immune responses were supported by Alcaligenes-stimulated CD11c+ dendritic cells (DCs) producing the Ab-enhancing cytokines TGF-β, B-cell-activating factor belonging to the TNF family, and IL-6 in PPs. These CD11c+ DCs did not migrate beyond the draining mesenteric lymph nodes. In the absence of antigen-specific mucosal Abs, the presence of Alcaligenes in PPs was greatly diminished. Thus, indigenous opportunistic bacteria uniquely inhabit PPs, leading to PP-DCs-initiated, local antigen-specific Ab production; this may involve the creation of an optimal symbiotic environment on the interior of the PPs.

Original languageEnglish
Pages (from-to)7419-7424
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number16
DOIs
Publication statusPublished - 2010 Apr 20

Keywords

  • Alcaligenes
  • Intratissue habitation
  • Peyer's patch

ASJC Scopus subject areas

  • General

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