SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells.
SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells.
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SARS-CoV-2病毒在肺泡巨噬细胞中的持续存在受IFN-γ和NK细胞控制。
DOI：
10.1038/s41590-023-01661-4
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发表时间：
2023-12
影响因子：
30.5
通讯作者：
Mueller-Trutwin, Michaela
中科院分区：
文献类型：
--
作者：
Huot, Nicolas;Planchais, Cyril;Rosenbaum, Pierre;Contreras, Vanessa;Jacquelin, Beatrice;Petitdemange, Caroline;Lazzerini, Marie;Beaumont, Emma;Orta-Resendiz, Aurelio;Rey, Felix A.;Reeves, R. Keith;Le Grand, Roger;Mouquet, Hugo;Mueller-Trutwin, Michaela
严重急性呼吸综合征冠状病毒2 (SARS-CoV-2) RNA通常在感染后几天或几周后在上呼吸道中无法检测到。在这里，我们使用猕猴病毒感染模型来解决SARS-CoV-2是否在体内持续存在以及哪些机制调节其持续存在。感染后6个月，在细支气管肺泡灌洗（BAL）巨噬细胞中检测到复制能力病毒。病毒在BAL巨噬细胞中的传播发生在细胞间，并被干扰素-γ (IFN-γ)抑制。IFN-γ的产生在BAL NKG2r+CD8+ T细胞和NKG2Alo自然杀伤（NK）细胞中最强，并且在刺突蛋白刺激后在NKG2Alo NK细胞中进一步增加。然而，感染持续病毒的猕猴NK细胞中IFN-γ的产生受损。此外，IFN-γ还增强了BAL巨噬细胞上主要组织相容性复合体(MHC)-E的表达，可能抑制NK细胞介导的杀伤。恒河猴携带持久性较低的病毒，装载了逃避mhc - e依赖性抑制的适应性NK细胞。我们的研究结果揭示了NK细胞和巨噬细胞之间的相互作用，该相互作用调节了SARS-CoV-2在巨噬细胞中的持久性，并由IFN-γ介导。Huot等人的研究表明，干扰素-γ (IFN-γ)调节食蟹猴支气管肺泡巨噬细胞中严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）在感染后长达18个月的持续存在。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA generally becomes undetectable in upper airways after a few days or weeks postinfection. Here we used a model of viral infection in macaques to address whether SARS-CoV-2 persists in the body and which mechanisms regulate its persistence. Replication-competent virus was detected in bronchioalveolar lavage (BAL) macrophages beyond 6 months postinfection. Viral propagation in BAL macrophages occurred from cell to cell and was inhibited by interferon-γ (IFN-γ). IFN-γ production was strongest in BAL NKG2r+CD8+ T cells and NKG2Alo natural killer (NK) cells and was further increased in NKG2Alo NK cells after spike protein stimulation. However, IFN-γ production was impaired in NK cells from macaques with persisting virus. Moreover, IFN-γ also enhanced the expression of major histocompatibility complex (MHC)-E on BAL macrophages, possibly inhibiting NK cell-mediated killing. Macaques with less persisting virus mounted adaptive NK cells that escaped the MHC-E-dependent inhibition. Our findings reveal an interplay between NK cells and macrophages that regulated SARS-CoV-2 persistence in macrophages and was mediated by IFN-γ. Huot et al. show that interferon-γ (IFN-γ) regulates the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in bronchoalveolar macrophages from cynomolgus macaques up to 18 months postinfection.
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影响因子：
16.6
作者：
Huot N;Rascle P;Petitdemange C;Contreras V;Stürzel CM;Baquero E;Harper JL;Passaes C;Legendre R;Varet H;Madec Y;Sauermann U;Stahl-Hennig C;Nattermann J;Saez-Cirion A;Le Grand R;Keith Reeves R;Paiardini M;Kirchhoff F;Jacquelin B;Müller-Trutwin M
通讯作者：
Müller-Trutwin M
影响因子：
7.3
作者：
Hou F;Xiao K;Tang L;Xie L
通讯作者：
Xie L
影响因子：
82.9
作者：
Huot N;Jacquelin B;Garcia-Tellez T;Rascle P;Ploquin MJ;Madec Y;Reeves RK;Derreudre-Bosquet N;Müller-Trutwin M
通讯作者：
Müller-Trutwin M
影响因子：
4.4
作者：
Kaiser, BK;Barahmand-pour, F;Strong, RK
通讯作者：
Strong, RK
影响因子：
6
作者：
Bortolotti D;Gentili V;Rizzo S;Rotola A;Rizzo R
通讯作者：
Rizzo R