γ-疱疹病毒感染抑制第2组固有淋巴细胞的2型特征，重新编程肺泡巨噬细胞
2023/03/21
摘要
哮喘的免疫失调与生命早期接触微生物的变化有关。γ疱疹病毒（γHV），例如Epstein-Barr病毒，是广泛存在的人类病毒，其建立终身感染并深刻地影响宿主免疫力。使用小鼠疱疹病毒4（MuHV-4）（一种小鼠γHV），我们显示在感染后，肺部驻留和募集的第2组先天淋巴细胞（ILC2）表现出响应于房尘螨而扩增和产生2型细胞因子的能力降低，从而有助于预防哮喘。相比之下，MuHV-4感染触发了肺ILC2产生GM-CSF，这导致单核细胞（Mos）分化为肺泡巨噬细胞（AM），而不促进其2型功能。因此，在γHV感染的情况下，ILC2是肺生态位内的必需细胞，其印记Mo衍生的AM的组织特异性身份并使其功能远远超过最初的急性感染。
Dampening type 2 properties of group 2 innate lymphoid cells by a gammaherpesvirus infection reprograms alveolar macrophages
Pauline Loos, Jérôme Baiwir, Céline Maquet, Justine Javaux, Rémy Sandor, François Lallemand, Thomas Marichal, Bénédicte Machiels, Laurent Gillet
Abstract
Immunological dysregulation in asthma is associated with changes in exposure to microorganisms early in life. Gammaherpesviruses (γHVs), such as Epstein-Barr virus, are widespread human viruses that establish lifelong infection and profoundly shape host immunity. Using murid herpesvirus 4 (MuHV-4), a mouse γHV, we show that after infection, lung-resident and recruited group 2 innate lymphoid cells (ILC2s) exhibit a reduced ability to expand and produce type 2 cytokines in response to house dust mites, thereby contributing to protection against asthma. In contrast, MuHV-4 infection triggers GM-CSF production by those lung ILC2s, which orders the differentiation of monocytes (Mos) into alveolar macrophages (AMs) without promoting their type 2 functions. In the context of γHV infection, ILC2s are therefore essential cells within the pulmonary niche that imprint the tissue-specific identity of Mo-derived AMs and shape their function well beyond the initial acute infection.
哮喘的免疫失调与生命早期接触微生物的变化有关。γ疱疹病毒（γHV），例如Epstein-Barr病毒，是广泛存在的人类病毒，其建立终身感染并深刻地影响宿主免疫力。使用小鼠疱疹病毒4（MuHV-4）（一种小鼠γHV），我们显示在感染后，肺部驻留和募集的第2组先天淋巴细胞（ILC2）表现出响应于房尘螨而扩增和产生2型细胞因子的能力降低，从而有助于预防哮喘。相比之下，MuHV-4感染触发了肺ILC2产生GM-CSF，这导致单核细胞（Mos）分化为肺泡巨噬细胞（AM），而不促进其2型功能。因此，在γHV感染的情况下，ILC2是肺生态位内的必需细胞，其印记Mo衍生的AM的组织特异性身份并使其功能远远超过最初的急性感染。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Sci Immunol. 2023 Feb 24;8(80):eabl9041. doi: 10.1126/sciimmunol.abl9041. Epub 2023 Feb 24.)
(Sci Immunol. 2023 Feb 24;8(80):eabl9041. doi: 10.1126/sciimmunol.abl9041. Epub 2023 Feb 24.)
Dampening type 2 properties of group 2 innate lymphoid cells by a gammaherpesvirus infection reprograms alveolar macrophages
Pauline Loos, Jérôme Baiwir, Céline Maquet, Justine Javaux, Rémy Sandor, François Lallemand, Thomas Marichal, Bénédicte Machiels, Laurent Gillet
Abstract
Immunological dysregulation in asthma is associated with changes in exposure to microorganisms early in life. Gammaherpesviruses (γHVs), such as Epstein-Barr virus, are widespread human viruses that establish lifelong infection and profoundly shape host immunity. Using murid herpesvirus 4 (MuHV-4), a mouse γHV, we show that after infection, lung-resident and recruited group 2 innate lymphoid cells (ILC2s) exhibit a reduced ability to expand and produce type 2 cytokines in response to house dust mites, thereby contributing to protection against asthma. In contrast, MuHV-4 infection triggers GM-CSF production by those lung ILC2s, which orders the differentiation of monocytes (Mos) into alveolar macrophages (AMs) without promoting their type 2 functions. In the context of γHV infection, ILC2s are therefore essential cells within the pulmonary niche that imprint the tissue-specific identity of Mo-derived AMs and shape their function well beyond the initial acute infection.
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