Divergent metabolic programmes control two populations of MAIT cells that protect the lung.
Divergent metabolic programmes control two populations of MAIT cells that protect the lung.
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DOI：
10.1038/s41556-023-01152-6
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发表时间：
2023-06
影响因子：
21.3
通讯作者：
中科院分区：
文献类型：
--
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虽然粘膜相关的不变T（MAIT）细胞提供快速的、先天的样应答，但它们不是预先设定的，并且已经描述了MAIT细胞在感染后的记忆样应答。然而，代谢对控制这些反应的重要性尚不清楚。在这里，用沙门氏菌疫苗株进行肺部免疫后，小鼠MAIT细胞作为单独的CD 127 − Klrg 1+和CD 127 + Klrg 1 −抗原适应群体扩增，这些群体在转录组，功能和肺组织中的定位方面有所不同。这些群体保持从稳定状态改变数月，作为稳定的单独MAIT细胞谱系，具有增强的效应程序和不同的代谢。CD 127 + MAIT细胞参与了一个充满活力的线粒体代谢程序，这对它们的维持和IL-17 A的合成至关重要。该方案得到高脂肪酸摄取和线粒体氧化的支持，并依赖于高度极化的线粒体和自噬。接种后，CD 127 + MAIT细胞保护小鼠免受肺炎链球菌感染。相比之下，Klrg 1 + MAIT细胞具有休眠但准备响应的线粒体，而是依赖于Hif 1a驱动的糖酵解来生存和产生IFN-γ。它们独立地应答抗原并参与对流感病毒的保护。这些代谢依赖性可以使得能够调节用于疫苗接种和免疫疗法的记忆样MAIT细胞应答。Riffelmacher等人表明，用活疫苗株免疫导致两种记忆样粘膜相关不变T细胞谱系的扩增，其具有不同的代谢需求、效应程序和保护能力。
Although mucosal-associated invariant T (MAIT) cells provide rapid, innate-like responses, they are not pre-set, and memory-like responses have been described for MAIT cells following infections. The importance of metabolism for controlling these responses, however, is unknown. Here, following pulmonary immunization with a Salmonella vaccine strain, mouse MAIT cells expanded as separate CD127−Klrg1+ and CD127+Klrg1− antigen-adapted populations that differed in terms of their transcriptome, function and localization in lung tissue. These populations remained altered from steady state for months as stable, separate MAIT cell lineages with enhanced effector programmes and divergent metabolism. CD127+ MAIT cells engaged in an energetic, mitochondrial metabolic programme, which was critical for their maintenance and IL-17A synthesis. This programme was supported by high fatty acid uptake and mitochondrial oxidation and relied on highly polarized mitochondria and autophagy. After vaccination, CD127+ MAIT cells protected mice against Streptococcus pneumoniae infection. In contrast, Klrg1+ MAIT cells had dormant but ready-to-respond mitochondria and depended instead on Hif1a-driven glycolysis to survive and produce IFN-γ. They responded antigen independently and participated in protection from influenza virus. These metabolic dependencies may enable tuning of memory-like MAIT cell responses for vaccination and immunotherapies. Riffelmacher et al. show that immunization with a live vaccine strain leads to the expansion of two memory-like mucosal-associated invariant T cell lineages with distinct metabolic needs, effector programmes and protective capacities.
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影响因子：
30.5
作者：
Kaech, SM;Tan, JT;Ahmed, R
通讯作者：
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作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
Saito, A
DOI：
10.1165/rcmb.2017-0290oc
发表时间：
2018-06-01
影响因子：
6.4
作者：
Hartmann, Nadine;McMurtrey, Curtis;Harriff, Melanie J.
通讯作者：
Harriff, Melanie J.