SARS-CoV-2 infection drives an inflammatory response in human adipose tissue through infection of adipocytes and macrophages.

Autor: Martínez-Colón GJ; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Ratnasiri K; Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA., Chen H; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Jiang S; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA., Zanley E; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Rustagi A; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Verma R; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Chen H; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA., Andrews JR; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA., Mertz KD; Institute of Pathology, Cantonal Hospital Baselland, 4410 Liestal, Switzerland., Tzankov A; Institute of Medical Genetics and Pathology, University Hospital of Basel, University of Basel, 4056 Basel, Switzerland., Azagury D; Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA., Boyd J; Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA., Nolan GP; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA., Schürch CM; Department of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, 72070 Tübingen, Germany., Matter MS; Institute of Medical Genetics and Pathology, University Hospital of Basel, University of Basel, 4056 Basel, Switzerland., Blish CA; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.; Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA., McLaughlin TL; Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Jazyk: angličtina
Zdroj: Science translational medicine [Sci Transl Med] 2022 Dec 07; Vol. 14 (674), pp. eabm9151. Date of Electronic Publication: 2022 Dec 07.
DOI: 10.1126/scitranslmed.abm9151
Abstrakt: Obesity, characterized by chronic low-grade inflammation of the adipose tissue, is associated with adverse coronavirus disease 2019 (COVID-19) outcomes, yet the underlying mechanism is unknown. To explore whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of adipose tissue contributes to pathogenesis, we evaluated COVID-19 autopsy cases and deeply profiled the response of adipose tissue to SARS-CoV-2 infection in vitro. In COVID-19 autopsy cases, we identified SARS-CoV-2 RNA in adipocytes with an associated inflammatory infiltrate. We identified two distinct cellular targets of infection: adipocytes and a subset of inflammatory adipose tissue-resident macrophages. Mature adipocytes were permissive to SARS-CoV-2 infection; although macrophages were abortively infected, SARS-CoV-2 initiated inflammatory responses within both the infected macrophages and bystander preadipocytes. These data suggest that SARS-CoV-2 infection of adipose tissue could contribute to COVID-19 severity through replication of virus within adipocytes and through induction of local and systemic inflammation driven by infection of adipose tissue-resident macrophages.
Databáze: MEDLINE