干擾素-λ對感染甲型流感病毒感染的調控

干擾素-λ在感染甲型流感病毒期間調節樹突狀細胞以促進T細胞免疫(Nat Immunol, IF: 23.530)

Interferon-λ modulates dendritic cells to facilitate T cell immunity during infection with influenza A virus

• Hemann EA, Green R, Turnbull JB, Langlois RA, Savan R, Gale M, Jr. Interferon-lambda modulates dendritic cells to facilitate T cell immunity during infection with influenza A virus. Nat Immunol 2019;20:1035-45.
• Michael Gale Jr, Department of Immunology, Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA, USA. 2Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USA. *e-mail: mgale@uw.edu.

Type III interferon (IFN-λ) is important for innate immune protection at mucosal surfaces and has therapeutic benefit against influenza A virus (IAV) infection. However, the mechanisms by which IFN-λ programs adaptive immune protection against IAV are undefined. Here we found that IFN-λ signaling in dendritic cell (DC) populations was critical for the development of protective IAV-specific CD8+ T cell responses. Mice lacking the IFN-λ receptor (Ifnlr1?/?) had blunted CD8+ T cell responses relative to wild type and exhibited reduced survival after heterosubtypic IAV re-challenge. Analysis of DCs revealed IFN-λ signaling directed the migration and function of CD103+ DCs for development of optimal antiviral CD8+ T cell responses, and bioinformatic analyses identified IFN-λ regulation of a DC IL-10 immunoregulatory network. Thus, IFN-λ serves a critical role in bridging innate and adaptive immunity from lung mucosa to lymph nodes to program DCs to direct effective T cell immunity against IAV.

III型干擾素（IFN-λ）對粘膜表面的先天免疫保護很重要，對甲型流感病毒（IAV）感染有治療作用。然而，IFN-λ程序對IAV的適應性免疫保護機制尚不明確。在這裡，我們發現樹突狀細胞（DC）群體中的IFN-λ信號傳導對保護性IAV特異性CD8+T細胞應答的發展至關重要。缺乏IFN-λ受體（ifnlr1?/?）的小鼠相對於野生型的CD8+T細胞應答減弱，並且在異源亞型IAV再攻擊後生存率降低。對DC的分析顯示，IFN-λ信號可引導CD103+DC的遷移和功能，從而產生最佳的抗病毒CD8+T細胞應答，且生物信息學分析鑒定了DC IL-10免疫調節網路的IFN-λ調節。因此，IFN-λ在肺粘膜到淋巴結的先天性和適應性免疫橋接中起著至關重要的作用，從而使樹突狀細胞能夠對IAV產生有效的T細胞免疫。

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