Viral PB1-F2 and host IFN-γ guide ILC2 and T cell activity during influenza virus infection.
Viral PB1-F2 and host IFN-γ guide ILC2 and T cell activity during influenza virus infection.
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DOI：
10.1073/pnas.2118535119
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发表时间：
2022-02-22
影响因子：
11.1
通讯作者：
Metzger DW
中科院分区：
文献类型：
--
作者：
Barman TK;Huber VC;Bonin JL;Califano D;Salmon SL;McKenzie ANJ;Metzger DW
对功能性免疫细胞可塑性的调节知之甚少。寄主环境线索是关键的，但病原体衍生的毒力因子可能的影响尚未被描述。我们使用了反向工程的甲型流感病毒，这些病毒在PB1-F2活性不同的情况下，分析了在宿主干扰素-γ存在或不存在的情况下小鼠的流感。在缺乏功能性PB1-F2和干扰素-γ的情况下，肺ILC2在病毒攻击后启动了强大的IL-5反应，从而改善了组织完整性和存活率。相反，功能性PB1-F2抑制IL-5+ILC2应答，并诱导主导的IL-13+CD8T细胞应答，而与宿主干扰素-γ无关。这些发现证明了在流感病毒感染期间，病毒毒力因子和宿主细胞因子之间在调节保护性肺免疫方面的关键相互作用。天然淋巴样细胞(ILCs)和T细胞的功能可塑性受宿主环境信号的调节，但病原体来源的毒力因子的影响尚未被描述。我们现在报道宿主干扰素-γ和病毒Pb1-F2毒力蛋白在调节ILC2和T细胞功能方面的相互作用，从而导致小鼠从流感病毒感染中恢复。在没有干扰素-γ的情况下，用含有非功能病毒PB1-F2的A/California/04/2009(CA04)H1N1病毒攻击的小鼠的肺ILC2启动了强烈的IL-5反应，这也导致了组织完整性的改善和生存的增加。相反，用表达完整功能的PB1-F2的波多黎各/8/1934(PR8)H1N1病毒攻击，抑制IL-5+ILC2应答，并诱导主导的IL-13+CD8T细胞应答，与宿主干扰素-γ表达无关。在用致死剂量的CA04攻击后，干扰素-γ缺陷小鼠的存活率和组织完整性得到了提高，但PR8病毒没有，并且抗性的增加依赖于干扰素-γR+ILC2的存在。不同功能PB1-F2活性的反向工程流感病毒诱导出与PB1-F2供体毒株相似的ILC2和T细胞表型，证明了PB1-F2病毒在宿主抵抗中的强大作用。这些结果表明，在流感感染过程中，病原体毒力因子与宿主干扰素-γ一起调节保护性肺免疫的能力。
The regulation of functional immune cell plasticity is poorly understood. Host environmental cues are critical, but the possible influence of pathogen-derived virulence factors has not been described. We have used reverse-engineered influenza A viruses that differ in PB1-F2 activity to analyze influenza in mice in the presence or absence of host interferon (IFN)-γ. In the absence of functional PB1-F2 and IFN-γ, lung ILC2s initiated robust IL-5 responses following viral challenge, which led to improved tissue integrity and survival. Conversely, functional PB1-F2 suppressed IL-5+ ILC2 responses and induced a dominant IL-13+ CD8 T cell response regardless of host IFN-γ. These findings demonstrate the critical interplay between the viral virulence factors and host cytokines in regulating protective pulmonary immunity during influenza virus infection. Functional plasticity of innate lymphoid cells (ILCs) and T cells is regulated by host environmental cues, but the influence of pathogen-derived virulence factors has not been described. We now report the interplay between host interferon (IFN)-γ and viral PB1-F2 virulence protein in regulating the functions of ILC2s and T cells that lead to recovery from influenza virus infection of mice. In the absence of IFN-γ, lung ILC2s from mice challenged with the A/California/04/2009 (CA04) H1N1 virus, containing nonfunctional viral PB1-F2, initiated a robust IL-5 response, which also led to improved tissue integrity and increased survival. Conversely, challenge with Puerto Rico/8/1934 (PR8) H1N1 virus expressing fully functional PB1-F2, suppressed IL-5+ ILC2 responses, and induced a dominant IL-13+ CD8 T cell response, regardless of host IFN-γ expression. IFN-γ–deficient mice had increased survival and improved tissue integrity following challenge with lethal doses of CA04, but not PR8 virus, and increased resistance was dependent on the presence of IFN-γR+ ILC2s. Reverse-engineered influenza viruses differing in functional PB1-F2 activity induced ILC2 and T cell phenotypes similar to the PB1-F2 donor strains, demonstrating the potent role of viral PB1-F2 in host resistance. These results show the ability of a pathogen virulence factor together with host IFN-γ to regulate protective pulmonary immunity during influenza infection.
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影响因子：
8
作者：
Califano D;Furuya Y;Roberts S;Avram D;McKenzie ANJ;Metzger DW
通讯作者：
Metzger DW
在流感病毒感染过程中，第2组IL-5的先天淋巴样细胞的产生受NKT细胞的调节。
影响因子：
6.7
作者：
Gorski SA;Hahn YS;Braciale TJ
通讯作者：
Braciale TJ
影响因子：
8
作者：
Donlan AN;Sutherland TE;Marie C;Preissner S;Bradley BT;Carpenter RM;Sturek JM;Ma JZ;Moreau GB;Donowitz JR;Buck GA;Serrano MG;Burgess SL;Abhyankar MM;Mura C;Bourne PE;Preissner R;Young MK;Lyons GR;Loomba JJ;Ratcliffe SJ;Poulter MD;Mathers AJ;Day AJ;Mann BJ;Allen JE;Petri WA Jr
通讯作者：
Petri WA Jr
影响因子：
14.2
作者：
Barlow, Jillian L.;Bellosi, Agustin;McKenzie, Andrew N. J.
通讯作者：
McKenzie, Andrew N. J.
影响因子：
6.7
作者：
Le Goffic R;Leymarie O;Chevalier C;Rebours E;Da Costa B;Vidic J;Descamps D;Sallenave JM;Rauch M;Samson M;Delmas B
通讯作者：
Delmas B