Neutrophil profiles of pediatric COVID-19 and multisystem inflammatory syndrome in children.

Autor:	Boribong BP; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA., LaSalle TJ; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Program in Health Sciences and Technology, Harvard Medical School & Massachusetts Institute of Technology, Boston, MA 02115, USA., Bartsch YC; Harvard Medical School, Boston, MA 02115, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA., Ellett F; Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Shriners Burns Hospital, Harvard Medical School, Boston, MA 02114, USA., Loiselle ME; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USA., Davis JP; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USA., Gonye ALK; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Sykes DB; Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA., Hajizadeh S; Harvard Medical School, Boston, MA 02115, USA; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Kreuzer J; Harvard Medical School, Boston, MA 02115, USA; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA., Pillai S; Harvard Medical School, Boston, MA 02115, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA., Haas W; Harvard Medical School, Boston, MA 02115, USA; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA., Edlow AG; Harvard Medical School, Boston, MA 02115, USA; Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Boston, MA 02114, USA; Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA., Fasano A; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA., Alter G; Harvard Medical School, Boston, MA 02115, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA., Irimia D; Center for Engineering in Medicine and Surgery, Department of Surgery, Massachusetts General Hospital, Shriners Burns Hospital, Harvard Medical School, Boston, MA 02114, USA., Sade-Feldman M; Harvard Medical School, Boston, MA 02115, USA; Center for Cancer Research, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA. Electronic address: msade-feldman@mgh.harvard.edu., Yonker LM; Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pediatrics, Massachusetts General Hospital, Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address: lyonker@mgh.harvard.edu.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2022 Dec 20; Vol. 3 (12), pp. 100848. Date of Electronic Publication: 2022 Nov 21.
DOI:	10.1016/j.xcrm.2022.100848
Abstrakt:	Multisystem inflammatory syndrome in children (MIS-C) is a delayed-onset, COVID-19-related hyperinflammatory illness characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigenemia, cytokine storm, and immune dysregulation. In severe COVID-19, neutrophil activation is central to hyperinflammatory complications, yet the role of neutrophils in MIS-C is undefined. Here, we collect blood from 152 children: 31 cases of MIS-C, 43 cases of acute pediatric COVID-19, and 78 pediatric controls. We find that MIS-C neutrophils display a granulocytic myeloid-derived suppressor cell (G-MDSC) signature with highly altered metabolism that is distinct from the neutrophil interferon-stimulated gene (ISG) response we observe in pediatric COVID-19. Moreover, we observe extensive spontaneous neutrophil extracellular trap (NET) formation in MIS-C, and we identify neutrophil activation and degranulation signatures. Mechanistically, we determine that SARS-CoV-2 immune complexes are sufficient to trigger NETosis. Our findings suggest that hyperinflammatory presentation during MIS-C could be mechanistically linked to persistent SARS-CoV-2 antigenemia, driven by uncontrolled neutrophil activation and NET release in the vasculature. Competing Interests: Declaration of interests M.S.-F. receives funding from Bristol-Myers Squibb. G.A. is a founder of Seromyx Systems, Inc. A.F. is co-founder of and stockholder in Alba Therapeutics. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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