Understanding SARS-CoV-2 associated immune pathology is crucial to develop pan-effective vaccines and treatments. Here we investigate the immune events from the acute state up to four weeks post SARS-CoV-2 infection, in non-human primates (NHP) with heterogeneous pulmonary pathology. We show a robust migration of CD16 expressing monocytes to the lungs occurring during the acute phase, and we describe two subsets of interstitial macrophages (HLA-DR + CD206 − ): a transitional CD11c + CD16 + cell population directly associated with IL-6 levels in plasma, and a long-lasting CD11b + CD16 + cell population. Trafficking of monocytes is mediated by TARC (CCL17) and associates with viral load measured in bronchial brushes. We also describe associations between disease outcomes and high levels of cell infiltration in lungs including CD11b + CD16 hi macrophages and CD11b + neutrophils. Accumulation of macrophages is 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 show less severe illness. Our results unravel cellular mechanisms of COVID-19 and suggest that NHP may be appropriate models to test immune therapies. Here, Fahlberg et al. describe the cellular immune response during acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates. The study identifies associations of monocytes and macrophage subtypes in lungs with disease outcome, IL-6 and IL-10 ratio in plasma, and viral replication in bronchial brushes.
【저자키워드】 SARS-CoV-2, Innate immunity, Infection, 【초록키워드】 COVID-19, Neutrophils, Monocytes, Macrophage, pathology, Vaccine, macrophages, Cellular immune response, IL-6, SARS-COV-2 infection, lung, outcome, immune, monocyte, Migration, Viral, Viral load, animals, non-human primates, viral replication, Lungs, Tryptophan, Kynurenine, understanding, Mild, plasma, IL-10, non-human primate, disease, HLA-DR, Therapies, association, CD11b, CD16, infiltration, IL-6 levels, Pulmonary pathology, acute phase, accumulation, heterogeneous, cellular mechanisms, anti-inflammatory response, subtype, CD11c, anti-inflammatory responses, CCL17, cell population, progressive COVID-19, NHP, Cell, event, interstitial, robust, identify, develop, detectable, less, long-lasting, expressing, subset, cellular mechanism, IL-6 level, 【제목키워드】 non-human primate, event,