Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19.

Autor: Sinha S; Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada., Rosin NL; Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada. nicole.rosin@ucalgary.ca., Arora R; Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada., Labit E; Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada., Jaffer A; Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada., Cao L; Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada., Farias R; Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.; Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada., Nguyen AP; Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.; Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada., de Almeida LGN; Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.; McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB, Canada., Dufour A; Department of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.; McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB, Canada., Bromley A; Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB, Canada., McDonald B; Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.; Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada., Gillrie MR; Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.; Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, Canada.; Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada., Fritzler MJ; Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.; Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada., Yipp BG; Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. bgyipp@ucalgary.ca.; Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. bgyipp@ucalgary.ca., Biernaskie J; Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada. jeff.biernaskie@ucalgary.ca.; Department of Surgery, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. jeff.biernaskie@ucalgary.ca.; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada. jeff.biernaskie@ucalgary.ca.; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada. jeff.biernaskie@ucalgary.ca.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2022 Jan; Vol. 28 (1), pp. 201-211. Date of Electronic Publication: 2021 Nov 15.
DOI: 10.1038/s41591-021-01576-3
Abstrakt: Although critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during Coronavirus Disease 2019 (COVID-19) ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying the beneficial effects of dexamethasone during severe COVID-19 remain elusive. Using single-cell RNA sequencing and plasma proteomics, we discovered that, compared to bacterial ARDS, COVID-19 was associated with expansion of distinct neutrophil states characterized by interferon (IFN) and prostaglandin signaling. Dexamethasone during severe COVID-19 affected circulating neutrophils, altered IFN active neutrophils, downregulated interferon-stimulated genes and activated IL-1R2 + neutrophils. Dexamethasone also expanded immunosuppressive immature neutrophils and remodeled cellular interactions by changing neutrophils from information receivers into information providers. Male patients had higher proportions of IFN active neutrophils and preferential steroid-induced immature neutrophil expansion, potentially affecting outcomes. Our single-cell atlas (see 'Data availability' section) defines COVID-19-enriched neutrophil states and molecular mechanisms of dexamethasone action to develop targeted immunotherapies for severe COVID-19.
(© 2021. The Author(s).)
Databáze: MEDLINE
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