Type I interferons drive MAIT cell functions against bacterial pneumonia.
Type I interferons drive MAIT cell functions against bacterial pneumonia.
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DOI：
10.1084/jem.20230037
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发表时间：
2023-10-02
影响因子：
15.3
通讯作者：
Barral, Patricia
中科院分区：
文献类型：
--
作者：
Lopez-Rodriguez, Juan Carlos;Hancock, Steven J.;Li, Kelin;Crotta, Stefania;Barrington, Christopher;Suarez-Bonnet, Alejandro;Priestnall, Simon L.;Aube, Jeffrey;Wack, Andreas;Klenerman, Paul;Bengoechea, Jose A.;Barral, Patricia
本报告确定了一个中心作用，I型干扰素在管理激活和效应功能的小鼠和人类MAIT细胞在肺部感染肺炎克雷伯氏菌。粘膜相关不变T（MAIT）细胞在肺中丰富，有助于宿主防御感染。在细菌感染期间，已经提出MAIT细胞活化需要T细胞受体（TCR）介导的对源自由抗原呈递分子MR 1呈递的核黄素合成途径的抗原的识别。MAIT细胞也可以被细胞因子以MR 1非依赖性方式激活，但MR 1依赖性与非依赖性信号对体内MAIT细胞功能的贡献仍不清楚。在这里，我们使用肺炎克雷伯氏菌作为细菌性肺炎的模型，并证明MAIT细胞激活是独立的MR 1和主要驱动的I型干扰素（IFN）。在克雷伯氏菌感染期间，I型IFN刺激鼠和人MAIT细胞的活化，诱导Th 1/细胞毒性转录程序，并调节MAIT细胞在肺内的位置。因此，肺MAIT细胞的过继转移或加强保护小鼠免受克雷伯氏菌感染，其中保护依赖于MAIT细胞上的直接I型IFN信号传导。这些发现揭示了I型IFN作为在细菌感染期间操纵MAIT细胞功能的新分子靶点。
This report identifies a central role for type I interferons in governing the activation and effector functions of murine and human MAIT cells during pulmonary infection with Klebsiella pneumoniae. Mucosal-associated invariant T (MAIT) cells are abundant in the lung and contribute to host defense against infections. During bacterial infections, MAIT cell activation has been proposed to require T cell receptor (TCR)–mediated recognition of antigens derived from the riboflavin synthesis pathway presented by the antigen-presenting molecule MR1. MAIT cells can also be activated by cytokines in an MR1-independent manner, yet the contribution of MR1-dependent vs. -independent signals to MAIT cell functions in vivo remains unclear. Here, we use Klebsiella pneumoniae as a model of bacterial pneumonia and demonstrate that MAIT cell activation is independent of MR1 and primarily driven by type I interferons (IFNs). During Klebsiella infection, type I IFNs stimulate activation of murine and human MAIT cells, induce a Th1/cytotoxic transcriptional program, and modulate MAIT cell location within the lungs. Consequently, adoptive transfer or boosting of pulmonary MAIT cells protect mice from Klebsiella infection, with protection being dependent on direct type I IFN signaling on MAIT cells. These findings reveal type I IFNs as new molecular targets to manipulate MAIT cell functions during bacterial infections.
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影响因子：
6.7
作者：
Ivin M;Dumigan A;de Vasconcelos FN;Ebner F;Borroni M;Kavirayani A;Przybyszewska KN;Ingram RJ;Lienenklaus S;Kalinke U;Stoiber D;Bengoechea JA;Kovarik P
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