Tuning of human MAIT cell activation by commensal bacteria species and MR1-dependent T-cell presentation.
Tuning of human MAIT cell activation by commensal bacteria species and MR1-dependent T-cell presentation.
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DOI：
10.1038/s41385-018-0072-x
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发表时间：
2018-11
影响因子：
8
通讯作者：
Unutmaz D
中科院分区：
文献类型：
--
作者：
Tastan C;Karhan E;Zhou W;Fleming E;Voigt AY;Yao X;Wang L;Horne M;Placek L;Kozhaya L;Oh J;Unutmaz D
人粘膜相关不变T（MAIT）细胞受体（TCR）通过MHC 1类相关分子MR 1识别细菌核黄素途径代谢物。然而，目前还不清楚MAIT细胞是否能区分许多人类微生物群物种。为了解决这一问题，我们开发了一种体外功能测定法，该测定法通过由表达MR 1的抗原呈递细胞（APC）刺激的针对MAIT-TCR（eMAIT-TCR）工程化的人T细胞进行。然后，我们筛选了来自不同门的47种微生物群相关细菌物种的eMAIT-TCR刺激能力。只有编码核黄素途径的细菌物种对MAIT-TCR有刺激作用。大多数物种是高刺激属于拟杆菌和变形菌门，而低/非刺激物种主要是放线菌或厚壁菌门。高刺激性细菌对MAIT细胞的激活也与它们分泌的核黄素水平或细菌感染巨噬细胞后的核黄素水平相关。值得注意的是，我们发现人类T细胞亚群也可以以MR 1限制的方式将核黄素代谢物呈递给MAIT细胞。这种T-T细胞介导的信号传导也从MAIT细胞诱导IFNγ、TNF和颗粒酶B，尽管水平低于专业APC。这些发现表明，MAIT细胞可以通过计算取决于抗原负荷和呈递细胞的TCR信号来区分和分类复杂的人类微生物群，并微调其功能反应。
Human mucosal-associated invariant T (MAIT) cell receptors (TCRs) recognize bacterial riboflavin pathway metabolites through the MHC class 1-related molecule MR1. However, it is unclear whether MAIT cells discriminate between many species of the human microbiota. To address this, we developed an in vitro functional assay through human T cells engineered for MAIT-TCRs (eMAIT-TCRs) stimulated by MR1-expressing antigen presenting cells (APC). We then screened 47 microbiota-associated bacterial species from different phyla for their eMAIT- TCR stimulatory capacities. Only bacteria species that encoded the riboflavin pathway were stimulatory for MAIT-TCRs. Most species that were high-stimulators belonged to Bacteroidetes and Proteobacteria phyla, whereas low/non-stimulator species were primarily Actinobacteria or Firmicutes. Activation of MAIT cells by high- vs low-stimulating bacteria also correlated with the level of riboflavin they secreted or after bacterial infection of macrophages. Remarkably, we found that human T cell subsets can also present riboflavin metabolites to MAIT cells in MR1- restricted fashion. This T-T cell mediated signaling also induced IFN𝛄, TNF and GranzymeB from MAIT cells, albeit at lower level than professional APC. These findings suggest that MAIT cells can discriminate and categorize complex human microbiota through computation of TCR signals depending on antigen load and presenting cells, and fine-tune their functional responses.
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影响因子：
3.7
作者：
Eberhard JM;Hartjen P;Kummer S;Schmidt RE;Bockhorn M;Lehmann C;Balagopal A;Hauber J;van Lunzen J;Schulze zur Wiesch J
通讯作者：
Schulze zur Wiesch J
影响因子：
15.9
作者：
Cui, Yue;Franciszkiewicz, Katarzyna;Lantz, Olivier
通讯作者：
Lantz, Olivier
影响因子：
3
作者：
Fahlen, Annika;Engstrand, Lars;Fry, Lionel
通讯作者：
Fry, Lionel
DOI：
10.1016/j.bbrc.2007.11.156
发表时间：
2008-02-08
影响因子：
3.1
作者：
Aldemir, Hatice
通讯作者：
Aldemir, Hatice
影响因子：
3.7
作者：
Gutiérrez-Preciado A;Torres AG;Merino E;Bonomi HR;Goldbaum FA;García-Angulo VA
通讯作者：
García-Angulo VA