Major alterations in the mononuclear phagocyte landscape associated with COVID-19 severity.
COVID-19
DCs
monocytes
pre-DCs
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
09 02 2021
09 02 2021
Historique:
entrez:
22
1
2021
pubmed:
23
1
2021
medline:
2
2
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33479167
pii: 2018587118
doi: 10.1073/pnas.2018587118
pmc: PMC8017719
pii:
doi:
Substances chimiques
Cytokines
0
Interferons
9008-11-1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Investigateurs
John Tyler Sandberg
(JT)
Helena Bergsten
(H)
Niklas K Björkström
(NK)
Susanna Brighenti
(S)
Marcus Buggert
(M)
Marta Butrym
(M)
Benedict J Chambers
(BJ)
Puran Chen
(P)
Martin Cornillet
(M)
Angelica Cuapio
(A)
Isabel Diaz Lozano
(ID)
Majda Dzidic
(M)
Johanna Emgård
(J)
Malin Flodström-Tullberg
(M)
Jean-Baptiste Gorin
(JB)
Sara Gredmark-Russ
(S)
Alvaro Haroun-Izquierdo
(A)
Laura Hertwig
(L)
Sadaf Kalsum
(S)
Jonas Klingström
(J)
Efthymia Kokkinou
(E)
Egle Kvedaraite
(E)
Hans-Gustaf Ljunggren
(HG)
Nicole Marquardt
(N)
Magdalini Lourda
(M)
Kimia T Maleki
(KT)
Karl-Johan Malmberg
(KJ)
Jakob Michaëlsson
(J)
Jenny Mjösberg
(J)
Kirsten Moll
(K)
Jagadeeswara Rao Muvva
(JR)
Anna Norrby-Teglund
(A)
Laura M Palma Medina
(LMP)
Tiphaine Parrot
(T)
Lena Radler
(L)
Emma Ringqvist
(E)
Johan K Sandberg
(JK)
Takuya Sekine
(T)
Tea Soini
(T)
Mattias Svensson
(M)
Janne Tynell
(J)
Andreas von Kries
(A)
David Wullimann
(D)
André Perez-Potti
(A)
Olga Rivera-Ballesteros
(O)
Christopher Maucourant
(C)
Renata Varnaite
(R)
Mira Akber
(M)
Lena Berglin
(L)
Demi Brownlie
(D)
Marco Giulio Loreti
(MG)
Ebba Sohlberg
(E)
Tobias Kammann
(T)
Elisabeth Henriksson
(E)
Kristoffer Strålin
(K)
Soo Aleman
(S)
Anders Sönnerborg
(A)
Lena Dillner
(L)
Anna Färnert
(A)
Hedvig Glans
(H)
Pontus Nauclér
(P)
Olav Rooyackers
(O)
Johan Mårtensson
(J)
Lars I Eriksson
(LI)
Björn P Persson
(BP)
Jonathan Grip
(J)
Christian Unge
(C)
Informations de copyright
Copyright © 2021 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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