Peterson Daniel A, McNulty Nathan P, Guruge Janaki L, Gordon Jeffrey I
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63108, USA.
Cell Host Microbe. 2007 Nov 15;2(5):328-39. doi: 10.1016/j.chom.2007.09.013.
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.
用正常肠道微生物群定殖无菌小鼠会引发细菌特异性IgA抗体反应。这些反应对微生物和宿主生物学的影响仍不清楚。因此，我们建立了一种悉生小鼠模型，其中微生物群减少到一个细菌物种，抗体库减少到针对该细菌荚膜多糖的单一单克隆IgA。将嗜热栖粪杆菌引入无菌野生型、免疫缺陷的Rag1(-/-)或携带产生IgA的杂交瘤细胞的Rag1(-/-)小鼠中。在没有IgA的情况下，嗜热栖粪杆菌会引发更强的先天性免疫反应，并通过诱导代谢宿主氧化产物的基因来应对这种反应。IgA可降低肠道促炎信号传导和细菌表位表达，从而在抑制氧化爆发与抗体对细菌适应性的负面影响之间取得平衡。这些结果强调了适应性免疫系统在建立可持续宿主-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著的菌株水平多样性。
