Dysregulation of the Leukocyte Signaling Landscape during Acute COVID-19.

Autor:	Turnbull IR; Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA., Fuchs A; Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA., Remy KE; Department of Pediatrics, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA., Kelly MP; Department of Orthopedic Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA., Frazier EP; Department of Orthopedic Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA., Ghosh S; Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA., Chang SW; Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA., Mazer M; Department of Anesthesia, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA., Hess A; Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA., Leonard J; Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA., Hoofnagle M; Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA., Colonna M; Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA., Hotchkiss RS; Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Jazyk:	angličtina
Zdroj:	Research square [Res Sq] 2021 Feb 16. Date of Electronic Publication: 2021 Feb 16.
DOI:	10.21203/rs.3.rs-244150/v1
Abstrakt:	The global COVID-19 pandemic has claimed the lives of more than 450,000 US citizens. Dysregulation of the immune system underlies the pathogenesis of COVID-19, with inflammation mediated local tissue injury to the lung in the setting of suppressed systemic immune function. To define the molecular mechanisms of immune dysfunction in COVID-19 we utilized a systems immunology approach centered on the circulating leukocyte phosphoproteome measured by mass cytometry. COVID-19 is associated with wholesale activation of a broad set of signaling pathways across myeloid and lymphoid cell populations. STAT3 phosphorylation predominated in both monocytes and T cells and was tightly correlated with circulating IL-6 levels. High levels of STAT3 phosphorylation was associated with decreased markers of myeloid cell maturation/activation and decreased ex-vivo T cell IFN-gamma production, demonstrating that during COVID-19 dysregulated cellular activation is associated with suppression of immune effector cell function. Collectively, these data reconcile the systemic inflammatory response and functional immunosuppression induced by COVID-19 and suggest STAT3 signaling may be the central pathophysiologic mechanism driving immune dysfunction in COVID-19.
Databáze:	MEDLINE
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