title: Indigenous opportunistic bacteria inhabit mammalian gut-associated lymphoid tissues and share a mucosal antibody-mediated symbiosis.
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-beta, 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.
authors.affiliation: Division of Mucosal Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Obata
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Goto
authors.forename: Jun
authors.initials: J
authors.lastname: Kunisawa
authors.forename: Shintaro
authors.initials: S
authors.lastname: Sato
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Hiromi
authors.initials: H
authors.lastname: Setoyama
authors.forename: Takahiro
authors.initials: T
authors.lastname: Matsuki
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nonaka
authors.forename: Naoko
authors.initials: N
authors.lastname: Shibata
authors.forename: Masashi
authors.initials: M
authors.lastname: Gohda
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kagiyama
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nochi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Yuki
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Fukuyama
authors.forename: Akira
authors.initials: A
authors.lastname: Mukai
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Shinzaki
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Fujihashi
authors.forename: Chihiro
authors.initials: C
authors.lastname: Sasakawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Iijima
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Goto
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Umesaki
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Benno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry*; D001419:Bacteria / Q000378:metabolism*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology*; D008198:Lymph Nodes / Q000276:immunology; D008221:Lymphoid Tissue / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D010581:Peyer's Patches / Q000276:immunology*; D012336:RNA, Ribosomal, 16S / Q000378:metabolism; D013154:Spleen / Q000276:immunology
chemical_list: D000906:Antibodies; D012336:RNA, Ribosomal, 16S