MAIT Cells in Respiratory Viral Infections in Mouse and Human.
MAIT Cells in Respiratory Viral Infections in Mouse and Human.
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DOI：
10.1615/critrevimmunol.2021040877
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发表时间：
2021
影响因子：
1.3
通讯作者：
Hinks TSC
中科院分区：
文献类型：
--
作者：
Long Y;Hinks TSC
粘膜相关不变T细胞(MAIT)首次被鉴定为细菌、分枝杆菌和真菌生物的特异性细胞，它检测由MHC相关蛋白1(MR1)呈递的微生物衍生的生物合成配体。最近，在这些古老而丰富的细胞中发现了两个意想不到的额外角色：在组织修复中依赖TCR的角色和在抗病毒宿主防御中不依赖TCR的角色。来自几类病毒疾病的数据表明，它们被细胞因子白介素12/15/18和I型干扰素激活的能力。MAIT细胞在粘膜表面大量存在，特别是在肺中，似乎是它们显著进化保守的一个主要原因是在早期对呼吸道感染(包括细菌和病毒)的先天防御中发挥了重要作用。在这里，我们回顾了它们依赖于TCR激活的证据，它们在甲型流感病毒中激活的观察人类数据，以及它们至少部分通过干扰素-γ介导的对严重甲型流感感染具有保护作用的体内证据。然后，我们调查了其他呼吸道病毒感染中出现的证据，包括最近在腺病毒感染中发挥重要佐剂作用的最近证据，特别是最近冠状病毒疫苗中使用的黑猩猩腺病毒，以及MAIT细胞反应和新冠肺炎(CoronaVirus-19)疾病不良后果之间的强烈关联的数据。我们推测这些发现的潜在翻译含义，要么使用皮质类固醇或抑制性配体来抑制有害的MAIT细胞反应，要么使用刺激性MR1配体来提高MAIT细胞的频率以增强固有的病毒防御。
Mucosal associated invariant T (MAIT) cells were first identified as specific for bacterial, mycobacterial and fungal organisms, which detect microbially-derived biosynthetic ligands presented by MHC-related protein 1 (MR1). More recently two unexpected, additional roles have been identified for these ancient and abundant cells: a TCR-dependent role in tissue repair and a TCR-independent role in antiviral host defence. Data from several classes of viral disease shows their capability for activation by the cytokines interleukin(IL)-12 / -15 / -18 and type I interferon. MAIT cells are abundant at mucosal surfaces, particularly in the lung, and it seems likely a primary reason for their striking evolutionary conservation is an important role in early innate defence against respiratory infections, including both bacteria and viruses. Here we review evidence for their TCR-independent activation, observational human data for their activation in influenza A virus, and in vivo murine evidence of their protection against severe influenza A infection, mediated at least partially via IFN-gamma. We then survey evidence emerging from other respiratory viral infections including recent evidence for an important adjuvant role in adenovirus infection, specifically chimpanzee adenoviruses used in recent coronavirus vaccines, and data for strong associations between MAIT cell responses and adverse outcomes from coronavirus-19 (COVID-19) disease. We speculate on potential translational implications of these findings, either using corticosteroids or inhibitory ligands to suppress deleterious MAIT cell responses, or the potential utility of stimulatory MR1 ligands to boost MAIT cell frequencies to enhance innate viral defences.