Department of Microbiology, Cornell University, Ithaca, NY 14853, USA; Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Cell Host Microbe. 2013 Nov 13;14(5):571-81. doi: 10.1016/j.chom.2013.10.009.
Gut mucosal barrier breakdown and inflammation have been associated with high levels of flagellin, the principal bacterial flagellar protein. Although several gut commensals can produce flagella, flagellin levels are low in the healthy gut, suggesting the existence of control mechanisms. We find that mice lacking the flagellin receptor Toll-like receptor 5 (TLR5) exhibit a profound loss of flagellin-specific immunoglobulins (Igs) despite higher total Ig levels in the gut. Ribotyping of IgA-coated cecal microbiota showed Proteobacteria evading antibody coating in the TLR5(-/-) gut. A diversity of microbiome members overexpressed flagellar genes in the TLR5(-/-) host. Proteobacteria and Firmicutes penetrated small intestinal villi, and flagellated bacteria breached the colonic mucosal barrier. In vitro, flagellin-specific Ig inhibited bacterial motility and downregulated flagellar gene expression. Thus, innate-immunity-directed development of flagellin-specific adaptive immune responses can modulate the microbiome's production of flagella in a three-way interaction that helps to maintain mucosal barrier integrity and homeostasis.
肠黏膜屏障的破坏和炎症与鞭毛蛋白（主要的细菌鞭毛蛋白）的高水平有关。虽然几种肠道共生菌可以产生鞭毛，但健康肠道中的鞭毛蛋白水平较低，这表明存在控制机制。我们发现，缺乏鞭毛蛋白受体 Toll 样受体 5（TLR5）的小鼠尽管肠道中总 Ig 水平较高，但表现出明显的鞭毛蛋白特异性免疫球蛋白（Igs）缺失。对 IgA 包被盲肠微生物组的核糖体分型显示，TLR5（-/-）肠道中逃避抗体包被的 Proteobacteria。TLR5（-/-）宿主中多种微生物组成员过度表达了鞭毛基因。变形菌和厚壁菌穿透了小肠绒毛，鞭毛菌突破了结肠黏膜屏障。在体外，鞭毛蛋白特异性 Ig 抑制了细菌的运动性，并下调了鞭毛基因的表达。因此，针对先天免疫的鞭毛蛋白特异性适应性免疫反应的发展可以调节微生物组产生鞭毛的方式，形成一种三方相互作用，有助于维持黏膜屏障的完整性和体内平衡。
