Indigenous opportunistic bacteria inhabit mammalian gut-associated lymphoid tissues and share a mucosal antibody-mediated symbiosis.
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.
Obata
Takashi
T
Division of Mucosal Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Goto
Yoshiyuki
Y
Kunisawa
Jun
J
Sato
Shintaro
S
Sakamoto
Mitsuo
M
Setoyama
Hiromi
H
Matsuki
Takahiro
T
Nonaka
Kazuhiko
K
Shibata
Naoko
N
Gohda
Masashi
M
Kagiyama
Yuki
Y
Nochi
Tomonori
T
Yuki
Yoshikazu
Y
Fukuyama
Yoshiko
Y
Mukai
Akira
A
Shinzaki
Shinichiro
S
Fujihashi
Kohtaro
K
Sasakawa
Chihiro
C
Iijima
Hideki
H
Goto
Masatoshi
M
Umesaki
Yoshinori
Y
Benno
Yoshimi
Y
Kiyono
Hiroshi
H
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
D000906:Antibodies; D012336:RNA, Ribosomal, 16S