Wang Xiaohui, Lin Xiang, Zheng Zihan, Lu Bingtai, Wang Jun, Tan Andy Hee-Meng, Zhao Meng, Loh Jia Tong, Ng Sze Wai, Chen Qian, Xiao Fan, Huang Enyu, Ko King-Hung, Huang Zhong, Li Jingyi, Kok Kin-Hang, Lu Gen, Liu Xiaohui, Lam Kong-Peng, Liu Wanli, Zhang Yuxia, Yuen Kwok-Yung, Mak Tak Wah, Lu Liwei
Department of Pathology and Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong, China.
Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China.
Nat Commun. 2021 Mar 26;12(1):1914. doi: 10.1038/s41467-021-22242-9.
Innate immunity is important for host defense by eliciting rapid anti-viral responses and bridging adaptive immunity. Here, we show that endogenous lipids released from virus-infected host cells activate lung γδ T cells to produce interleukin 17 A (IL-17A) for early protection against H1N1 influenza infection. During infection, the lung γδ T cell pool is constantly supplemented by thymic output, with recent emigrants infiltrating into the lung parenchyma and airway to acquire tissue-resident feature. Single-cell studies identify IL-17A-producing γδ T (Tγδ17) cells with a phenotype of TCRγδCD3AQP3CXCR6 in both infected mice and patients with pneumonia. Mechanistically, host cell-released lipids during viral infection are presented by lung infiltrating CD1d B-1a cells to activate IL-17A production in γδ T cells via γδTCR-mediated IRF4-dependent transcription. Reduced IL-17A production in γδ T cells is detected in mice either lacking B-1a cells or with ablated CD1d in B cells. Our findings identify a local host-immune crosstalk and define important cellular and molecular mediators for early innate defense against lung viral infection.
固有免疫通过引发快速的抗病毒反应和衔接适应性免疫，对宿主防御至关重要。在此，我们表明，病毒感染的宿主细胞释放的内源性脂质激活肺γδT细胞，使其产生白细胞介素17A（IL-17A），从而对H1N1流感感染提供早期保护。在感染期间，肺γδT细胞库不断由胸腺输出补充，近期迁出的细胞浸润到肺实质和气道中以获得组织驻留特征。单细胞研究在感染小鼠和肺炎患者中均鉴定出具有TCRγδCD3AQP3CXCR6表型的产生IL-17A的γδT（Tγδ17）细胞。从机制上讲，病毒感染期间宿主细胞释放的脂质由肺浸润的CD1d B-1a细胞呈递，以通过γδTCR介导的IRF4依赖性转录激活γδT细胞中IL-17A的产生。在缺乏B-1a细胞或B细胞中CD1d被敲除的小鼠中，检测到γδT细胞中IL-17A产生减少。我们的研究结果确定了一种局部宿主-免疫串扰，并定义了针对肺部病毒感染的早期固有防御的重要细胞和分子介质。
