Impaired function and delayed regeneration of dendritic cells in COVID-19.


Journal

PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921

Informations de publication

Date de publication:
10 2021
Historique:
received: 28 06 2021
accepted: 23 09 2021
revised: 18 10 2021
pubmed: 7 10 2021
medline: 3 11 2021
entrez: 6 10 2021
Statut: epublish

Résumé

Disease manifestations in COVID-19 range from mild to severe illness associated with a dysregulated innate immune response. Alterations in function and regeneration of dendritic cells (DCs) and monocytes may contribute to immunopathology and influence adaptive immune responses in COVID-19 patients. We analyzed circulating DC and monocyte subsets in 65 hospitalized COVID-19 patients with mild/moderate or severe disease from acute illness to recovery and in healthy controls. Persisting reduction of all DC subpopulations was accompanied by an expansion of proliferating Lineage-HLADR+ cells lacking DC markers. Increased frequency of CD163+ CD14+ cells within the recently discovered DC3 subpopulation in patients with more severe disease was associated with systemic inflammation, activated T follicular helper cells, and antibody-secreting cells. Persistent downregulation of CD86 and upregulation of programmed death-ligand 1 (PD-L1) in conventional DCs (cDC2 and DC3) and classical monocytes associated with a reduced capacity to stimulate naïve CD4+ T cells correlated with disease severity. Long-lasting depletion and functional impairment of DCs and monocytes may have consequences for susceptibility to secondary infections and therapy of COVID-19 patients.

Identifiants

pubmed: 34614036
doi: 10.1371/journal.ppat.1009742
pii: PPATHOGENS-D-21-01334
pmc: PMC8523079
doi:

Substances chimiques

Antigens, CD 0
PDCD1 protein, human 0
Programmed Cell Death 1 Receptor 0

Types de publication

Clinical Trial Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1009742

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

Références

PLoS One. 2014 Apr 22;9(4):e95192
pubmed: 24755770
Cell Mol Immunol. 2021 Oct;18(10):2325-2333
pubmed: 34413488
Proc Natl Acad Sci U S A. 2021 Feb 9;118(6):
pubmed: 33479167
Annu Rev Immunol. 2021 Apr 26;39:131-166
pubmed: 33481643
J Med Virol. 2020 Jul;92(7):791-796
pubmed: 32181911
Ann Intern Med. 2020 Aug 18;173(4):268-277
pubmed: 32374815
Nat Med. 2020 Oct;26(10):1623-1635
pubmed: 32807934
Sci Immunol. 2020 Jul 15;5(49):
pubmed: 32669287
Science. 2020 Sep 4;369(6508):1210-1220
pubmed: 32788292
PLoS One. 2014 Jul 08;9(7):e102137
pubmed: 25003524
Nat Med. 2020 Sep;26(9):1428-1434
pubmed: 32661393
J Infect Dis. 2021 Feb 24;223(4):562-567
pubmed: 33206973
Cell Res. 2015 Oct;25(10):1121-36
pubmed: 26358190
Cell. 2021 Feb 18;184(4):861-880
pubmed: 33497610
Immunity. 2019 Sep 17;51(3):573-589.e8
pubmed: 31474513
Cell. 2020 Oct 1;183(1):158-168.e14
pubmed: 32979941
N Engl J Med. 2020 Feb 20;382(8):727-733
pubmed: 31978945
Cell. 2021 Apr 1;184(7):1671-1692
pubmed: 33743212
Nat Med. 2020 Jun;26(6):842-844
pubmed: 32398875
Cell. 2020 Jun 25;181(7):1489-1501.e15
pubmed: 32473127
J Clin Invest. 2020 Dec 1;130(12):6290-6300
pubmed: 32784290
Nat Commun. 2021 Mar 5;12(1):1428
pubmed: 33674591
Lancet. 2020 Mar 28;395(10229):1054-1062
pubmed: 32171076
Cell. 2020 Nov 12;183(4):996-1012.e19
pubmed: 33010815
Cancer Res. 2016 Aug 1;76(15):4332-46
pubmed: 27325645
Sci Immunol. 2020 Sep 17;5(51):
pubmed: 32943497
Immunity. 2021 Apr 13;54(4):797-814.e6
pubmed: 33765436
Cell. 2021 Apr 1;184(7):1836-1857.e22
pubmed: 33713619
Nucleic Acids Res. 2013 Jan;41(Database issue):D1040-6
pubmed: 23203888
J Immunol. 2021 Aug 15;207(4):1099-1111
pubmed: 34312258
J Exp Med. 2013 Jul 29;210(8):1635-46
pubmed: 23835848
Nat Immunol. 2021 May;22(5):620-626
pubmed: 33674800
Clin Immunol. 2005 Sep;116(3):225-35
pubmed: 15964242
J Exp Med. 2021 Apr 5;218(4):
pubmed: 33533916
Science. 2020 Sep 4;369(6508):
pubmed: 32669297
Immunity. 2020 Aug 18;53(2):335-352.e8
pubmed: 32610077
Nature. 2020 Nov;587(7833):270-274
pubmed: 32726801
Cell. 2020 Dec 10;183(6):1479-1495.e20
pubmed: 33171100
Science. 2021 Feb 5;371(6529):
pubmed: 33408181
Nat Med. 2020 Jul;26(7):1070-1076
pubmed: 32514174
Immunity. 2015 Sep 15;43(3):591-604
pubmed: 26362266
Cell Rep. 2019 Dec 10;29(11):3736-3750.e8
pubmed: 31825848
Nat Commun. 2020 Oct 8;11(1):5086
pubmed: 33033248
Lancet. 2020 Feb 15;395(10223):497-506
pubmed: 31986264
Nature. 2020 Dec;588(7837):315-320
pubmed: 32846427
Cell Host Microbe. 2020 Jun 10;27(6):883-890.e2
pubmed: 32407669
Nature. 2020 Aug;584(7821):463-469
pubmed: 32717743
Cell. 2020 Sep 17;182(6):1419-1440.e23
pubmed: 32810438
Cell. 2020 Sep 17;182(6):1401-1418.e18
pubmed: 32810439
Nat Biotechnol. 2020 Aug;38(8):970-979
pubmed: 32591762
Immunity. 2020 Oct 13;53(4):864-877.e5
pubmed: 32791036
Cytometry A. 2020 Dec 6;:
pubmed: 33280254
Science. 2016 Apr 8;352(6282):189-96
pubmed: 27124452
Front Immunol. 2019 Aug 13;10:1907
pubmed: 31456804
Nat Immunol. 2020 Nov;21(11):1336-1345
pubmed: 32887977
Immunity. 2021 Jan 12;54(1):44-52.e3
pubmed: 33338412
Nat Cell Biol. 2021 May;23(5):538-551
pubmed: 33972731
Cell Host Microbe. 2020 Jun 10;27(6):992-1000.e3
pubmed: 32320677
Neoplasia. 2005 Dec;7(12):1112-22
pubmed: 16354594
Immunity. 2008 May;28(5):710-22
pubmed: 18468462
Science. 2020 Aug 7;369(6504):718-724
pubmed: 32661059
Crit Care. 2020 Aug 28;24(1):530
pubmed: 32859241
Curr Hypertens Rep. 2020 Jan 8;22(1):4
pubmed: 31916032

Auteurs

Elena Winheim (E)

Institute for Immunology, Biomedical Center (BMC), Faculty of Medicine, LMU Munich; Munich, Germany.

Linus Rinke (L)

Institute for Immunology, Biomedical Center (BMC), Faculty of Medicine, LMU Munich; Munich, Germany.

Konstantin Lutz (K)

Institute for Immunology, Biomedical Center (BMC), Faculty of Medicine, LMU Munich; Munich, Germany.

Anna Reischer (A)

Department of Medicine III, University Hospital, LMU Munich; Munich, Germany.
Laboratory for Translational Cancer Immunology, Gene Center, LMU Munich; Munich, Germany.

Alexandra Leutbecher (A)

Department of Medicine III, University Hospital, LMU Munich; Munich, Germany.
Laboratory for Translational Cancer Immunology, Gene Center, LMU Munich; Munich, Germany.

Lina Wolfram (L)

Institute for Immunology, Biomedical Center (BMC), Faculty of Medicine, LMU Munich; Munich, Germany.

Lisa Rausch (L)

Institute for Immunology, Biomedical Center (BMC), Faculty of Medicine, LMU Munich; Munich, Germany.

Jan Kranich (J)

Institute for Immunology, Biomedical Center (BMC), Faculty of Medicine, LMU Munich; Munich, Germany.

Paul R Wratil (PR)

Max von Pettenkofer Institute of Hygiene and Medical Microbiology, Faculty of Medicine & Gene Center, Virology, National Reference Center for Retroviruses, LMU Munich; Munich, Germany.
German Center for Infection Research (DZIF), partner site Munich, Germany.

Johanna E Huber (JE)

Institute for Immunology, Biomedical Center (BMC), Faculty of Medicine, LMU Munich; Munich, Germany.

Dirk Baumjohann (D)

Institute for Immunology, Biomedical Center (BMC), Faculty of Medicine, LMU Munich; Munich, Germany.
Medical Clinic III for Oncology, Hematology, Immuno-Oncology and Rheumatology, University Hospital Bonn, University of Bonn, Bonn, Germany.

Simon Rothenfusser (S)

Division of Clinical Pharmacology, University Hospital, LMU Munich; Munich, Germany.
Unit Clinical Pharmacology (EKLiP), Helmholtz Zentrum München, German Research Center for Environmental Health (HMGU), Neuherberg, Germany.

Benjamin Schubert (B)

Institute of Computational Biology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
Department of Mathematics, Technical University of Munich, Garching, Germany.

Anne Hilgendorff (A)

Institute for Lung Biology and Disease and Comprehensive Pneumology Center with the CPC-M bioArchive, Helmholtz Center Munich, Member of the German Center for Lung Research (DZL), Munich, Germany.
Center for Comprehensive Developmental Care (CDeCLMU), Dr. Von Haunersche Children's Hospital, University Hospital LMU Munich; Munich, Germany.

Johannes C Hellmuth (JC)

Department of Medicine III, University Hospital, LMU Munich; Munich, Germany.
COVID-19 Registry of the LMU Munich (CORKUM), University Hospital, LMU Munich; Munich, Germany.

Clemens Scherer (C)

COVID-19 Registry of the LMU Munich (CORKUM), University Hospital, LMU Munich; Munich, Germany.
Department of Medicine I, University Hospital, LMU Munich; Munich, Germany.

Maximilian Muenchhoff (M)

Max von Pettenkofer Institute of Hygiene and Medical Microbiology, Faculty of Medicine & Gene Center, Virology, National Reference Center for Retroviruses, LMU Munich; Munich, Germany.
German Center for Infection Research (DZIF), partner site Munich, Germany.
COVID-19 Registry of the LMU Munich (CORKUM), University Hospital, LMU Munich; Munich, Germany.

Michael von Bergwelt-Baildon (M)

Department of Medicine III, University Hospital, LMU Munich; Munich, Germany.
COVID-19 Registry of the LMU Munich (CORKUM), University Hospital, LMU Munich; Munich, Germany.
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ); Heidelberg, Germany.

Konstantin Stark (K)

COVID-19 Registry of the LMU Munich (CORKUM), University Hospital, LMU Munich; Munich, Germany.
Department of Medicine I, University Hospital, LMU Munich; Munich, Germany.

Tobias Straub (T)

Core Facility Bioinformatics, Biomedical Center, LMU Munich; Munich, Germany.

Thomas Brocker (T)

Institute for Immunology, Biomedical Center (BMC), Faculty of Medicine, LMU Munich; Munich, Germany.

Oliver T Keppler (OT)

Max von Pettenkofer Institute of Hygiene and Medical Microbiology, Faculty of Medicine & Gene Center, Virology, National Reference Center for Retroviruses, LMU Munich; Munich, Germany.
German Center for Infection Research (DZIF), partner site Munich, Germany.

Marion Subklewe (M)

Department of Medicine III, University Hospital, LMU Munich; Munich, Germany.
Laboratory for Translational Cancer Immunology, Gene Center, LMU Munich; Munich, Germany.

Anne B Krug (AB)

Institute for Immunology, Biomedical Center (BMC), Faculty of Medicine, LMU Munich; Munich, Germany.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH