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DOI10.1073/pnas.2018587118
Major alterations in the mononuclear phagocyte landscape associated with COVID-19 severity
Kvedaraite E.; Hertwig L.; Sinha I.; Ponzetta A.; Myrberg I.H.; Lourda M.; Dzidic M.; Akber M.; Klingström J.; Folkesson E.; Muvva J.R.; Chen P.; Gredmark-Russ S.; Brighenti S.; Norrby-Teglund A.; Eriksson L.I.; Rooyackers O.; Aleman S.; Strålin K.; Ljunggren H.-G.; Ginhoux F.; Björkström N.K.; Henter J.-I.; Svensson M.; Karolinska KI/K COVID-19 Study Group
发表日期2021
ISSN00278424
卷号118期号:6
英文摘要Dendritic cells (DCs) and monocytes are crucial mediators of innate and adaptive immune responses during viral infection, but misdirected responses by these cells may contribute to immunopathology. Here, we performed high-dimensional flow cytometry-analysis focusing on mononuclear phagocyte (MNP) lineages in SARS-CoV-2-infected patients with moderate and severe COVID-19. We provide a deep and comprehensive map of the MNP landscape in COVID-19. A redistribution of monocyte subsets toward intermediate monocytes and a general decrease in circulating DCs was observed in response to infection. Severe disease coincided with the appearance of monocytic myeloid-derived suppressor cell-like cells and a higher frequency of pre-DC2. Furthermore, phenotypic alterations in MNPs, and their late precursors, were cell-lineage-specific and associated either with the general response against SARS-CoV-2 or COVID-19 severity. This included an interferon-imprint in DC1s observed in all patients and a decreased expression of the coinhibitory molecule CD200R in pre-DCs, DC2s, and DC3 subsets of severely sick patients. Finally, unsupervised analysis revealed that the MNP profile, alone, pointed to a cluster of COVID-19 nonsurvivors. This study provides a reference for the MNP response to SARS-CoV-2 infection and unravels mononuclear phagocyte dysregulations associated with severe COVID-19. © 2021 National Academy of Sciences. All rights reserved.
英文关键词COVID-19; DCs; Monocytes; Pre-DCs
语种英语
scopus关键词cytokine; interferon; adult; dendritic cell; epidemiology; female; human; immunology; male; metabolism; middle aged; monocyte; mononuclear phagocyte; severity of illness index; Sweden; virology; Adult; COVID-19; Cytokines; Dendritic Cells; Female; Humans; Interferons; Male; Middle Aged; Monocytes; Mononuclear Phagocyte System; SARS-CoV-2; Severity of Illness Index; Sweden
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/180780
作者单位Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, 171 77, Sweden; Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, 171 77, Sweden; Department of Infectious Diseases, Karolinska University Hospital, Stockholm, 171 77, Sweden; Department of Physiology and Pharmacology, Section for Anesthesiology and Intensive Care, Karolinska Institutet, Stockholm, 171 77, Sweden; Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, Stockholm, 171 77, Sweden; Division of Anesthesiology and Intensive Care, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Huddinge, 141 52, Sweden; Division of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, 171 77, Sweden; Singapore Immunology Network, Agency for Science, Technology and Research, BIOPOLIS, Singapore, 138648, Singapore; Shanghai Ins...
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Kvedaraite E.,Hertwig L.,Sinha I.,et al. Major alterations in the mononuclear phagocyte landscape associated with COVID-19 severity[J],2021,118(6).
APA Kvedaraite E..,Hertwig L..,Sinha I..,Ponzetta A..,Myrberg I.H..,...&Karolinska KI/K COVID-19 Study Group.(2021).Major alterations in the mononuclear phagocyte landscape associated with COVID-19 severity.Proceedings of the National Academy of Sciences of the United States of America,118(6).
MLA Kvedaraite E.,et al."Major alterations in the mononuclear phagocyte landscape associated with COVID-19 severity".Proceedings of the National Academy of Sciences of the United States of America 118.6(2021).
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