Indigenous opportunistic bacteria inhabit mammalian gut-associated lymphoid tissues and share a mucosal antibody-mediated symbiosis
Indigenous opportunistic bacteria inhabit mammalian gut-associated lymphoid tissues and share a mucosal antibody-mediated symbiosis
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DOI：
10.1073/pnas.1001061107
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发表时间：
2010-04-20
影响因子：
11.1
通讯作者：
Kiyono, Hiroshi
中科院分区：
文献类型：
--
作者：
Obata, Takashi;Goto, Yoshiyuki;Kiyono, Hiroshi
固有细菌与胃肠道（GI）中的粘膜Ab一起形成天然同居小生境。在这里，我们报告说，机会细菌，主要是产碱菌属物种，特别是栖息主机派尔集合淋巴结（PP）和孤立的淋巴滤泡，与相关的优先诱导抗原特异性粘膜伊加抗体在胃肠道。产碱菌被确定为占主导地位的细菌对内部的PP从幼稚的，特定的病原体，但不是从无菌小鼠。将组织内未培养的产碱菌经口转移到无菌小鼠中导致受体PP内存在产碱菌。该结果进一步得到粘膜中抗原特异性Ab产生细胞的诱导的支持（例如，PP），但不是全身隔室（例如，脾）。在猴和人中也观察到PP内优先存在产碱菌和肠道分泌型伊加Ab的相关诱导。局部粘膜Ab介导的共生免疫应答由产碱菌刺激的CD 11 c（+）树突状细胞（DC）支持，这些树突状细胞在PP中产生Ab增强细胞因子TGF-β、属于TNF家族的B细胞活化因子和IL-6。这些CD 11 c（+）DC没有迁移到肠系膜引流淋巴结以外。在没有抗原特异性粘膜抗体的情况下，PP中产碱杆菌的存在大大减少。因此，土著机会细菌独特地栖息于PP，导致PP-DCs启动的局部抗原特异性Ab产生;这可能涉及在PP内部创建最佳共生环境。
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 naive, 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.