Elson Charles O, Alexander Katie L
Dig Dis. 2015;33(2):131-136. doi: 10.1159/000369534. Epub 2015 Apr 22.
The comprehensive collection of bacterial species, termed microbiota, within human and other mammalian hosts has profound effects on both innate and adaptive immunity. Multiple host innate mechanisms contribute to intestinal homeostasis, including epithelial production of protective mucin layers maintaining spatial segregation in the intestine as well as epithelial cell secretion of a broad range of antimicrobial peptides. Additionally, epithelial cells employ autophagy to contain and eliminate invading bacteria; interestingly, genetic variants in specific autophagy genes are linked to susceptibility to Crohn's disease. Innate lymphoid cells, which rapidly respond to cytokine and microbial signals, have emerged as important regulators of the intestinal immune response to the microbiota. With regard to adaptive immunity, specific microbial species stimulate induction of regulatory T cells while others induce effector T cells within the gut. Such stimulation is subject to dysregulation during inflammation and disease, contributing to 'dysbiosis' or an abnormal microbiota composition that has been associated with a variety of immune-mediated inflammatory disorders, including celiac disease. The microbiota communicates with the immune system and vice versa; thus, an abnormal microbiota composition likely translates into an altered host immune response, though the exact mechanisms of such are not yet clear. Immunoglobulin A plays a critical role in limiting bacterial access to the host and in maintaining mutualism with the microbiota. Perturbation of the mucosal barrier via infection or other means can induce effector T cells reactive to the intestinal microbiota, and these cells can persist as memory cells for extended periods of time and potentially serve as pathogenic effector cells upon re-encounter with antigen. Health is associated with a diverse microbiota that functions to maintain the balance between T effector and T regulatory cells in the intestine. Whether dysbiosis can be reversed in immune-mediated disease, thus restoring health, is a question of intense interest for this active area of research.
人类和其他哺乳动物宿主体内的细菌种类综合集合，即微生物群，对先天性免疫和适应性免疫都有深远影响。多种宿主先天性机制有助于肠道稳态，包括上皮细胞产生保护性粘蛋白层以维持肠道内的空间隔离，以及上皮细胞分泌多种抗菌肽。此外，上皮细胞利用自噬来容纳和消除入侵细菌；有趣的是，特定自噬基因的遗传变异与克罗恩病易感性相关。先天性淋巴细胞能快速响应细胞因子和微生物信号，已成为肠道对微生物群免疫反应的重要调节因子。关于适应性免疫，特定微生物种类刺激调节性T细胞的诱导，而其他微生物种类则在肠道内诱导效应性T细胞。这种刺激在炎症和疾病期间会失调，导致“生态失调”或微生物群组成异常，这与包括乳糜泻在内的多种免疫介导的炎症性疾病有关。微生物群与免疫系统相互作用；因此，微生物群组成异常可能转化为宿主免疫反应改变，尽管其确切机制尚不清楚。免疫球蛋白A在限制细菌进入宿主以及维持与微生物群的共生关系方面起着关键作用。通过感染或其他方式破坏黏膜屏障可诱导对肠道微生物群有反应的效应性T细胞，这些细胞可作为记忆细胞长期存在，并可能在再次接触抗原时充当致病效应细胞。健康与多样化的微生物群有关，该微生物群的功能是维持肠道内效应性T细胞和调节性T细胞之间的平衡。在免疫介导的疾病中生态失调是否可以逆转从而恢复健康，是这个活跃研究领域备受关注的问题。
