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黏膜相关恒定T细胞与共生菌和致病菌的相互作用:在儿童抗菌免疫中的潜在作用

Mucosal-Associated Invariant T Cell Interactions with Commensal and Pathogenic Bacteria: Potential Role in Antimicrobial Immunity in the Child.

作者信息

Ghazarian Liana, Caillat-Zucman Sophie, Houdouin Véronique

机构信息

INSERM UMR1149, Centre de Recherche sur l'Inflammation, Université Paris Diderot, Paris, France.

Laboratoire d'Immunologie, Hôpital Saint Louis, AP-HP, Paris, France.

出版信息

Front Immunol. 2017 Dec 15;8:1837. doi: 10.3389/fimmu.2017.01837. eCollection 2017.

Abstract

Mucosal-associated invariant T (MAIT) cells are unconventional CD3CD161 T lymphocytes that recognize vitamin B2 (riboflavin) biosynthesis precursor derivatives presented by the MHC-I related protein, MR1. In humans, their T cell receptor is composed of a Vα7.2-Jα33/20/12 chain, combined with a restricted set of Vβ chains. MAIT cells are very abundant in the liver (up to 40% of resident T cells) and in mucosal tissues, such as the lung and gut. In adult peripheral blood, they represent up to 10% of circulating T cells, whereas they are very few in cord blood. This large number of MAIT cells in the adult likely results from their gradual expansion with age following repeated encounters with riboflavin-producing microbes. Upon recognition of MR1 ligands, MAIT cells have the capacity to rapidly eliminate bacterially infected cells through the production of inflammatory cytokines (IFNγ, TNFα, and IL-17) and cytotoxic effector molecules (perforin and granzyme B). Thus, MAIT cells may play a crucial role in antimicrobial defense, in particular at mucosal sites. In addition, MAIT cells have been implicated in diseases of non-microbial etiology, including autoimmunity and other inflammatory diseases. Although their participation in various clinical settings has received increased attention in adults, data in children are scarce. Due to their innate-like characteristics, MAIT cells might be particularly important to control microbial infections in the young age, when long-term protective adaptive immunity is not fully developed. Herein, we review the data showing how MAIT cells may control microbial infections and how they discriminate pathogens from commensals, with a focus on models relevant for childhood infections.

摘要

黏膜相关恒定T(MAIT)细胞是非常规的CD3CD161 T淋巴细胞,可识别由MHC-I相关蛋白MR1呈递的维生素B2(核黄素)生物合成前体衍生物。在人类中,它们的T细胞受体由Vα7.2-Jα33/20/12链组成,并与一组受限的Vβ链结合。MAIT细胞在肝脏中非常丰富(占驻留T细胞的40%),在黏膜组织如肺和肠道中也很丰富。在成人外周血中,它们占循环T细胞的比例高达10%,而在脐带血中则很少。成人中大量的MAIT细胞可能是由于它们随着年龄的增长,在反复接触产生核黄素的微生物后逐渐扩增所致。一旦识别出MR1配体,MAIT细胞就有能力通过产生炎性细胞因子(IFNγ、TNFα和IL-17)和细胞毒性效应分子(穿孔素和颗粒酶B)迅速清除细菌感染的细胞。因此,MAIT细胞可能在抗菌防御中发挥关键作用,特别是在黏膜部位。此外,MAIT细胞还与非微生物病因的疾病有关,包括自身免疫性疾病和其他炎症性疾病。尽管它们在各种临床环境中的参与在成人中受到了越来越多的关注,但儿童的数据却很少。由于其固有样特性,MAIT细胞在幼儿期控制微生物感染可能尤为重要,因为此时长期保护性适应性免疫尚未完全发育。在此,我们综述了相关数据,展示了MAIT细胞如何控制微生物感染以及它们如何区分病原体与共生菌,重点关注与儿童感染相关的模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1071/5736530/e01243e78b09/fimmu-08-01837-g001.jpg

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