肠道微生物与免疫的研究进展

Progress in research on interaction of intestinal microbiota and immunity

对于人体,肠道是最大的免疫器官,它由造血细胞(巨噬细胞、树突细胞和T细胞)和非造血细胞(上皮细胞、帕内特细胞和杯状细胞)组成。同时在它里面寄居着上亿万的微生物,这些微生物群与宿主免疫系统共同维持内环境的稳态.肠道微生物对炎性反应(包括自身免疫疾病、过敏症等)的发展有着重要的影响。现在人们正在进行肠道微生物对不同类型免疫反应的影响机制的研究,肠道微生物对宿主免疫系统的成熟有直接的影响,它对免疫球蛋白A(immunoglobulin A,IgA)的诱导、CD4^+T细胞包括Th1、Th17和调节性T细胞(CD4^+、CD25^+、Foxp3^+)的调节以及抗菌肽(antimicrobial peptides,AMPs)的表达有重要作用,菌群产生的许多分子可能影响这些免疫反应。同时,大量的基础和临床研究已经证明调控肠道微生物是一种高效治疗和控制疾病的方法,如果这些机制被完全弄清楚,就可以通过益生菌/益生元来调控肠道微生物而达到治疗疾病的目的。为此,本研究前沿性地综述了肠道共生微生物与免疫系统的相互作用以及与人类健康的密切关系。

The human intestinal tract is the largest immune organ in the body and comprises cells from nonhemopoietic（epithelia,Paneth cells,goblet cells）and hemopoietic（macrophages,dendritic cells,T-cells）,and have trillions of microbes collectively.The microbiota and host immune system communicate with each other to mutually maintain homeostasis.Gut microbiota can have important consequences for the development of inflammatory diseases,including autoimmune diseases and allergy,and the specific mechanisms by which the gut commensals impel the development of diverse types of immune responses are beginning to be understood.Gut microbiota has been shown to direct maturation of the host immune system,to play an important role in the induction of CD4~＋T cell（including Th1,Th17 and Foxp3~＋regulatory T cell）and immunoglobulin A（IgA）,and the expression of antimicrobial peptides.Intestinal colonization of altered Schaedler flora（ASF）resulted in activation and de novo generation of colonic Tregcells.Failure to activate Treg cells resulted in the induction of T helper 17（Th17）and Th1 cell responses.Thus,microbiota colonization-induced Treg cell responses are a fundamental intrinsic mechanism to induce and maintain host-intestinal microbial T cell mutualism.Commensals are rapidly killed by macrophages,intestinal dendritic cells（DCs）can keep small numbers of live commensals for a few days,which makes DCs selectively induce IgA.The commensal-loaded DCs are confined to the mucosal immune compartment by the mesenteric lymph nodes,which assure that immune responses to gut bacteria are induced locally,without potentially damaging systemic immune responses.The production of cathelicidin related antimicrobial peptide（CRAMP）by insulin secretingβ-cells was controlled by short chain fatty acids produced by the gut microbiota.Therefore,gut microbiota manipulations in non-bese diabetic（NOD）mice modulated CRAMP production and inflammation in the pancreatic islets,exposing that the gut microbiota directly shape the pancreatic immune environment and autoimmune diabetes development.There may be numerous molecules produced by gut microbes that affect these immune responses.Meanwhile,targeting gut microbiota might be an effective strategy to overcome diseases,which was proved by many experimental and clinical researches.Accordingly,if these mechanisms are fully understood,diseases can be treated with probiotics/prebiotics to regulate gut microbes. Here,this review advances our understanding of the interactions between resident microbes and the immune system,and the implications of these findings for human health.