Acetate differentially regulates IgA reactivity to commensal bacteria
Acetate differentially regulates IgA reactivity to commensal bacteria
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DOI：
10.1038/s41586-021-03727-5
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发表时间：
2021-07-14
期刊：
影响因子：
64.8
通讯作者：
Ohno, Hiroshi
中科院分区：
文献类型：
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作者：
Takeuchi, Tadashi;Miyauchi, Eiji;Ohno, Hiroshi
肠道中细菌定植及其容纳之间的平衡对于人类与细菌之间的共生关系是必不可少的。维持粘膜表面稳态的一种成分是免疫球蛋白A（伊加），它是哺乳动物中含量最高的免疫球蛋白（1，2）。几项研究揭示了多反应性伊加的重要特征（3，4），它是在没有肠道细菌的情况下自然产生的。然而，考虑到肠道环境的动态变化，仍然不确定肠道反应性伊加池是如何形成的，以及这种伊加如何影响微生物群落。在这里，我们表明，醋酸盐的主要肠道微生物代谢产物之一，不仅增加了伊加的生产在结肠，但也改变了伊加池的能力，以结合到特定的微生物，包括肠球菌。在小鼠单克隆大肠杆菌，这属于Enterocellales，但不是与主要的大肠杆菌thetaiotaomicron，这表明，醋酸盐指导选择性伊加结合某些微生物的IgA反应性伊加和伊加库的变化的诱导。从机制上讲，醋酸盐协调了上皮细胞和免疫细胞之间的相互作用，诱导微生物刺激的CD4 T细胞以支持T细胞依赖性伊加的产生，因此改变了这些细菌在结肠内的定位。总的来说，我们确定了肠道微生物代谢产物在调节差异伊加产生以维持粘膜稳态中的作用。
The balance between bacterial colonization and its containment in the intestine is indispensable for the symbiotic relationship between humans and their bacteria. One component to maintain homeostasis at the mucosal surfaces is immunoglobulin A (IgA), the most abundant immunoglobulin in mammals(1,2). Several studies have revealed important characteristics of poly-reactive IgA(3,4), which is produced naturally without commensal bacteria. Considering the dynamic changes within the gut environment, however, it remains uncertain how the commensal-reactive IgA pool is shaped and how such IgA affects the microbial community. Here we show that acetate-one of the major gut microbial metabolites-not only increases the production of IgA in the colon, but also alters the capacity of the IgA pool to bind to specific microorganisms including Enterobacterales. Induction of commensal-reactive IgA and changes in the IgA repertoire by acetate were observed in mice monocolonized with Escherichia coli, which belongs to Enterobacterales, but not with the major commensal Bacteroides thetaiotaomicron, which suggests that acetate directs selective IgA binding to certain microorganisms. Mechanistically, acetate orchestrated the interactions between epithelial and immune cells, induced microbially stimulated CD4 T cells to support T-cell-dependent IgA production and, as a consequence, altered the localization of these bacteria within the colon. Collectively, we identified a role for gut microbial metabolites in the regulation of differential IgA production to maintain mucosal homeostasis.