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ILC1 Confer Early Host Protection at Initial Sites of Viral Infection.
Cell ( IF 45.5 ) Pub Date : 2017-Nov-02 , DOI: 10.1016/j.cell.2017.09.052
Orr-El Weizman 1 , Nicholas M Adams 1 , Iona S Schuster 2 , Chirag Krishna 3 , Yuri Pritykin 3 , Colleen Lau 1 , Mariapia A Degli-Esposti 2 , Christina S Leslie 3 , Joseph C Sun 4 , Timothy E O'Sullivan 1
Affiliation  

Infection is restrained by the concerted activation of tissue-resident and circulating immune cells. Whether tissue-resident lymphocytes confer early antiviral immunity at local sites of primary infection prior to the initiation of circulating responses is not well understood. Furthermore, the kinetics of initial antiviral responses at sites of infection remain unclear. Here, we show that tissue-resident type 1 innate lymphoid cells (ILC1) serve an essential early role in host immunity through rapid production of interferon (IFN)-γ following viral infection. Ablation of Zfp683-dependent liver ILC1 lead to increased viral load in the presence of intact adaptive and innate immune cells critical for mouse cytomegalovirus (MCMV) clearance. Swift production of interleukin (IL)-12 by tissue-resident XCR1+ conventional dendritic cells (cDC1) promoted ILC1 production of IFN-γ in a STAT4-dependent manner to limit early viral burden. Thus, ILC1 contribute an essential role in viral immunosurveillance at sites of initial infection in response to local cDC1-derived proinflammatory cytokines.

中文翻译:

ILC1 在病毒感染的初始部位提供早期宿主保护。

通过组织驻留和循环免疫细胞的协同激活来抑制感染。在循环反应开始之前,组织驻留淋巴细胞是否在原发感染的局部部位赋予早期抗病毒免疫尚不清楚。此外,感染部位初始抗病毒反应的动力学仍不清楚。在这里,我们表明组织驻留的 1 型先天淋巴细胞 (ILC1) 通过在病毒感染后快速产生干扰素 (IFN)-γ 在宿主免疫中发挥重要的早期作用。在存在对小鼠巨细胞病毒 (MCMV) 清除至关重要的完整适应性和先天免疫细胞的情况下,Zfp683 依赖性肝脏 ILC1 的消融导致病毒载量增加。组织驻留 XCR1 +迅速产生白细胞介素 (IL)-12常规树突状细胞 (cDC1) 以 STAT4 依赖性方式促进 ILC1 产生 IFN-γ,以限制早期病毒负荷。因此,ILC1 在初始感染部位的病毒免疫监视中发挥重要作用,以响应局部 cDC1 衍生的促炎细胞因子。
更新日期:2017-10-19
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