We investigated the immune events following SARS-CoV-2 infection, from the acute inflammatory state up to four weeks post infection, in non-human primates (NHP) with heterogeneous pulmonary pathology. The acute phase was characterized by a robust and rapid migration of monocytes expressing CD16 from the blood and concomitant increase in CD16+ macrophages in the lungs. We identified two subsets of interstitial macrophages (HLA-DR+ CD206-), a transitional CD11c+ CD16+ cell population that was directly associated with IL-6 levels in plasma, and one long lasting CD11b+ CD16+ cell population. Strikingly, levels of monocytes were a correlate of viral replication in bronchial brushes and we discovered TARC (CCL17) as a new potential mediator of myeloid recruitment to the lungs. Worse disease outcomes were associated with high levels of cell infiltration in lungs including CD11b+ CD16hi macrophages and CD11b+ neutrophils. Accumulation of macrophages was long-lasting and detectable even in animals with mild or no signs of disease. Interestingly, animals with anti-inflammatory responses including high IL-10:IL-6 and kynurenine to tryptophan ratios had less signs of disease. Our results unravel cellular mechanisms of COVID-19 and suggest that NHP may be appropriate models to test immune therapies.

中文翻译：

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SARS-CoV-2感染的非人类灵长类动物中急性，分辨或进行性COVID-19的细胞事件

我们在具有异质性肺病的非人类灵长类动物（NHP）中调查了SARS-CoV-2感染后从急性炎症到感染后四周的免疫事件。急性期的特征是从血液中表达CD16的单核细胞强劲快速迁移，并伴随着肺中CD16 +巨噬细胞的增加。我们确定了间质性巨噬细胞的两个子集（HLA-DR + CD206-），一个与血浆IL-6水平直接相关的过渡性CD11c + CD16 +细胞群，和一个持久的CD11b + CD16 +细胞群。令人惊讶的是，单核细胞水平是支气管刷中病毒复制的相关因素，我们发现TARC（CCL17）是髓样募集至肺的新潜在媒介。较差的疾病结局与肺中高水平的细胞浸润有关，包括CD11b + CD16hi巨噬细胞和CD11b +中性粒细胞。即使在患有轻度或无疾病迹象的动物中，巨噬细胞的蓄积也是持久且可检测的。有趣的是，具有抗炎反应（包括高IL-10：IL-6和犬尿氨酸与色氨酸的比率）的动物患病的迹象较少。我们的研究结果揭示了COVID-19的细胞机制，并暗示NHP可能是测试免疫疗法的合适模型。