IgA response to symbiotic bacteria as a mediator of gut homeostasis
IgA response to symbiotic bacteria as a mediator of gut homeostasis
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DOI：
10.1016/j.chom.2007.09.013
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发表时间：
2007-11-01
影响因子：
30.3
通讯作者：
Gordon, Jeffrey I.
中科院分区：
文献类型：
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作者：
Peterson, Daniel A.;McNulty, Nathan P.;Gordon, Jeffrey I.
具有正常肠道微生物群的无菌小鼠的定殖激发细菌特异性伊加抗体应答。这些反应对微生物和宿主生物学的影响仍然不清楚。因此，我们开发了一种无菌小鼠模型，其中微生物群减少到一种细菌物种，并且抗体库减少到针对细菌的荚膜多糖的单个单克隆伊加。将多形拟杆菌引入无菌野生型、免疫缺陷Rag 1（-/-）或携带IgA产生杂交瘤细胞的Rag 1（-/-）小鼠中。无伊加时，B.多形核小体激发更强的先天免疫应答，并通过诱导代谢宿主氧化产物的基因对该应答作出反应。伊加减少肠道促炎信号传导和细菌表位表达，从而平衡氧化爆发的抑制与抗体对细菌适应性的负面影响。这些结果强调了适应性免疫系统在建立可持续的宿主-微生物关系中的关键作用。细菌表位表达的免疫选择可能有助于该生态系统中显着的菌株水平的多样性。
Colonization of germ-free mice with a normal gut microbiota elicits bacteria-specific IgA antibody responses. The effects of these responses on microbial and host biology remain poorly defined. Therefore, we developed a gnotobiotic mouse model where the microbiota is reduced to one bacterial species, and the antibody repertoire to a single, monoclonal IgA against the bacterium's capsular polysaccharide. Bacteroides thetaiotaomicron was introduced into germ-free wild-type, immunodeficient Rag1(-/-), or Rag1(-/-) mice harboring IgA-producing hybridoma cells. Without IgA, B. thetaiotaomicron elicits a more robust innate immune response and reacts to this response by inducing genes that metabolize host oxidative products. IgA reduces intestinal proinflammatory signaling and bacterial epitope expression, thereby balancing suppression of the oxidative burst with the antibody's negative impact on bacterial fitness. These results underscore the adaptive immune system's critical role in establishing a sustainable host-microbial relationship. Immunoselection of bacterial epitope expression may contribute to the remarkable strain-level diversity in this ecosystem.