Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates
Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates
Abstract 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.
Datta PK、Fahlberg MD、Blair RV、Haupt EH、Lehmicke G、Golden N、Roy CJ、Bohm RP、Maness NJ、Zenere G、Russell-Lodrigue KE、Penney TP、Fischer T、Monjure CJ、Threeton BM、Rappaport J、Doyle-Meyers LA、Midkiff CC、Vaccari M
Tulane National Primate Research Center||Tulane University School of MedicineTulane National Primate Research CenterTulane National Primate Research Center||Tulane University School of MedicineTulane National Primate Research CenterTulane National Primate Research CenterTulane National Primate Research CenterTulane National Primate Research Center||Tulane University School of MedicineTulane National Primate Research Center||Tulane University School of MedicineTulane National Primate Research Center||Tulane University School of MedicineTulane National Primate Research CenterTulane National Primate Research CenterTulane National Primate Research CenterTulane National Primate Research Center||Tulane University School of MedicineTulane National Primate Research Center||Tulane University School of MedicineTulane National Primate Research CenterTulane National Primate Research Center||Tulane University School of MedicineTulane National Primate Research CenterTulane National Primate Research CenterTulane National Primate Research Center||Tulane University School of Medicine
基础医学细胞生物学分子生物学
Datta PK,Fahlberg MD,Blair RV,Haupt EH,Lehmicke G,Golden N,Roy CJ,Bohm RP,Maness NJ,Zenere G,Russell-Lodrigue KE,Penney TP,Fischer T,Monjure CJ,Threeton BM,Rappaport J,Doyle-Meyers LA,Midkiff CC,Vaccari M.Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates[EB/OL].(2025-03-28)[2025-05-07].https://www.biorxiv.org/content/10.1101/2020.07.21.213777.点此复制
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