Identification and Phenotype of MAIT Cells in Cattle and Their Response to Bacterial Infections.

Identification and Phenotype of MAIT Cells in Cattle and Their Response to Bacterial Infections.
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DOI:
10.3389/fimmu.2021.627173
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发表时间:
2021
影响因子:
7.3
通讯作者:
Benedictus L
Benedictus L
中科院分区:
医学2区
文献类型:
--
作者:
Edmans MD;Connelley TK;Jayaraman S;Vrettou C;Vordermeier M;Mak JYW;Liu L;Fairlie DP;Maze EA;Chrun T;Klenerman P;Eckle SBG;Tchilian E;Benedictus L

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粘膜相关不变T细胞(MAIT)是一类利用半不变T细胞受体α链的先天T细胞,受高度保守的抗原提呈分子MR1的限制。MR1是细菌和真菌产生的微生物核黄素生物合成衍生代谢物。MAIT细胞与其感知来自细菌来源的配体的能力一致,与对各种细菌感染的免疫反应有关,如分枝杆菌属、沙门氏菌属。和大肠埃希菌。到目前为止,MAIT细胞已经在人类、非人类灵长类动物和小鼠身上进行了研究。然而,它们只是通过基于聚合酶链式反应的方法在牛身上进行了推定的鉴定;没有进行表型或功能分析。在这里,我们利用MR1四聚体和高通量TCR测序鉴定了牛的MAIT细胞群。牛MAIT细胞的表型分析揭示了与人和小鼠MAIT细胞高度相似的特征,包括表达TRAV1-TRAJ33TCRα链,与组织定位无关的效应记忆表型,以及转录因子PLZF和EBES的表达。我们检测了外周血和多种组织中MAIT细胞的频率,发现牛MAIT细胞在粘膜组织和肠系膜淋巴结中都有丰富的表达。体外培养的牛MAIT细胞对5-OP-RU和核黄素生物合成能力细菌的刺激反应良好。此外,在患有乳房炎的奶牛中,牛奶中的MAIT细胞的频率增加。在受到牛结核和人畜共患病病原体牛分枝杆菌的攻击后,外周血MAIT细胞表达了更高水平的穿孔素。因此,MAIT细胞与牛对两种主要细菌感染的免疫反应有关。这些数据表明,MAIT细胞在功能上高度保守,牛是研究MAIT细胞在重要的人畜共患感染中作用的优秀大型动物模型。
Mucosal-associated invariant T (MAIT) cells are a population of innate-like T cells that utilize a semi-invariant T cell receptor (TCR) α chain and are restricted by the highly conserved antigen presenting molecule MR1. MR1 presents microbial riboflavin biosynthesis derived metabolites produced by bacteria and fungi. Consistent with their ability to sense ligands derived from bacterial sources, MAIT cells have been associated with the immune response to a variety of bacterial infections, such as Mycobacterium spp., Salmonella spp. and Escherichia coli. To date, MAIT cells have been studied in humans, non-human primates and mice. However, they have only been putatively identified in cattle by PCR based methods; no phenotypic or functional analyses have been performed. Here, we identified a MAIT cell population in cattle utilizing MR1 tetramers and high-throughput TCR sequencing. Phenotypic analysis of cattle MAIT cells revealed features highly analogous to those of MAIT cells in humans and mice, including expression of an orthologous TRAV1-TRAJ33 TCR α chain, an effector memory phenotype irrespective of tissue localization, and expression of the transcription factors PLZF and EOMES. We determined the frequency of MAIT cells in peripheral blood and multiple tissues, finding that cattle MAIT cells are enriched in mucosal tissues as well as in the mesenteric lymph node. Cattle MAIT cells were responsive to stimulation by 5-OP-RU and riboflavin biosynthesis competent bacteria in vitro. Furthermore, MAIT cells in milk increased in frequency in cows with mastitis. Following challenge with virulent Mycobacterium bovis, a causative agent of bovine tuberculosis and a zoonosis, peripheral blood MAIT cells expressed higher levels of perforin. Thus, MAIT cells are implicated in the immune response to two major bacterial infections in cattle. These data suggest that MAIT cells are functionally highly conserved and that cattle are an excellent large animal model to study the role of MAIT cells in important zoonotic infections.
DOI: 10.1111/imcb.12021
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发表时间: 1995-08-04
期刊: SCIENCE
影响因子: 56.9
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来自多发性硬化症脑病变的αβT细胞受体显示与MAIT细胞相关的特征。
DOI: 10.1212/nxi.0000000000000107
发表时间: 2015-08
期刊: Neurology(R) neuroimmunology & neuroinflammation
影响因子: --
作者:
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发表时间: 2009-04-24
期刊: BMC genomics
影响因子: 4.4
作者:
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通讯作者: Morrison WI