Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans.
Betacoronavirus
/ immunology
COVID-19
Coronavirus Infections
/ immunology
Cytokines
/ blood
DNA, Bacterial
/ blood
Dendritic Cells
/ immunology
Female
Flow Cytometry
HLA-DR Antigens
/ analysis
Humans
Immunity
Immunity, Innate
Immunoglobulins
/ blood
Inflammation Mediators
/ blood
Interferon Type I
/ metabolism
Leukocytes, Mononuclear
/ immunology
Lipopolysaccharides
/ blood
Male
Myeloid Cells
/ immunology
Pandemics
Pneumonia, Viral
/ immunology
SARS-CoV-2
Signal Transduction
Single-Cell Analysis
Systems Biology
TOR Serine-Threonine Kinases
/ metabolism
Transcription, Genetic
Transcriptome
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
04 09 2020
04 09 2020
Historique:
received:
05
05
2020
revised:
10
07
2020
accepted:
04
08
2020
pubmed:
14
8
2020
medline:
20
9
2020
entrez:
14
8
2020
Statut:
ppublish
Résumé
Coronavirus disease 2019 (COVID-19) represents a global crisis, yet major knowledge gaps remain about human immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong and Atlanta, Georgia, United States. In the peripheral blood mononuclear cells (PBMCs) of COVID-19 patients, we observed reduced expression of human leukocyte antigen class DR (HLA-DR) and proinflammatory cytokines by myeloid cells as well as impaired mammalian target of rapamycin (mTOR) signaling and interferon-α (IFN-α) production by plasmacytoid dendritic cells. By contrast, we detected enhanced plasma levels of inflammatory mediators-including EN-RAGE, TNFSF14, and oncostatin M-which correlated with disease severity and increased bacterial products in plasma. Single-cell transcriptomics revealed a lack of type I IFNs, reduced HLA-DR in the myeloid cells of patients with severe COVID-19, and transient expression of IFN-stimulated genes. This was consistent with bulk PBMC transcriptomics and transient, low IFN-α levels in plasma during infection. These results reveal mechanisms and potential therapeutic targets for COVID-19.
Identifiants
pubmed: 32788292
pii: science.abc6261
doi: 10.1126/science.abc6261
pmc: PMC7665312
doi:
Substances chimiques
Cytokines
0
DNA, Bacterial
0
HLA-DR Antigens
0
Immunoglobulins
0
Inflammation Mediators
0
Interferon Type I
0
Lipopolysaccharides
0
MTOR protein, human
EC 2.7.1.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1210-1220Subventions
Organisme : NIAID NIH HHS
ID : R38 AI140299
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI090023
Pays : United States
Organisme : NIAID NIH HHS
ID : U24 AI120134
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI057266
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201400006C
Pays : United States
Organisme : NIH HHS
ID : S10 OD021763
Pays : United States
Organisme : NIH HHS
ID : S10 OD026799
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI048638
Pays : United States
Organisme : NIH HHS
ID : S10 OD018220
Pays : United States
Organisme : NIH HHS
ID : P51 OD011132
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI148576
Pays : United States
Informations de copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Références
PLoS One. 2014 Apr 22;9(4):e95192
pubmed: 24755770
Cell Host Microbe. 2016 Feb 10;19(2):181-93
pubmed: 26867177
Front Immunol. 2018 Mar 19;9:576
pubmed: 29616048
Nat Metab. 2020 Mar;2(3):233-242
pubmed: 32694777
Nat Rev Immunol. 2017 Jul;17(7):407-420
pubmed: 28436424
F1000Res. 2017 May 26;6:748
pubmed: 28663787
EBioMedicine. 2014 Nov 1;1(1):64-71
pubmed: 25685830
Science. 2020 Aug 7;369(6504):718-724
pubmed: 32661059
Ann Intern Med. 1993 Oct 15;119(8):771-8
pubmed: 8379598
JAMA. 2020 Apr 7;323(13):1239-1242
pubmed: 32091533
J Clin Invest. 2020 May 1;130(5):2620-2629
pubmed: 32217835
J Infect Dis. 1999 Nov;180(5):1584-9
pubmed: 10515819
Cell. 2016 Jan 28;164(3):564-78
pubmed: 26824662
Nat Med. 2020 Jun;26(6):842-844
pubmed: 32398875
Cell. 2020 Jun 25;181(7):1489-1501.e15
pubmed: 32473127
Cell. 2020 May 28;181(5):1016-1035.e19
pubmed: 32413319
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Science. 2020 Sep 4;369(6508):
pubmed: 32669297
MMWR Morb Mortal Wkly Rep. 2020 Apr 03;69(13):382-386
pubmed: 32240123
Semin Immunopathol. 2017 Jul;39(5):529-539
pubmed: 28466096
Mol Immunol. 2020 Apr 13;122:38-48
pubmed: 32298873
Paediatr Respir Rev. 2017 Jun;23:40-49
pubmed: 28416135
Mol Cell. 2019 Feb 7;73(3):446-457.e6
pubmed: 30612880
Nat Immunol. 2014 Feb;15(2):195-204
pubmed: 24336226
Signal Transduct Target Ther. 2020 Mar 27;5(1):33
pubmed: 32296069
Nat Immunol. 2008 Oct;9(10):1157-64
pubmed: 18758466
Cell Mol Immunol. 2020 May;17(5):533-535
pubmed: 32203188
Nat Med. 2020 Jul;26(7):1070-1076
pubmed: 32514174
Lancet. 2020 Feb 15;395(10223):497-506
pubmed: 31986264
Front Immunol. 2020 May 01;11:827
pubmed: 32425950
Sci Immunol. 2020 Jul 15;5(49):
pubmed: 32669287
Immunology. 2012 Jun;136(2):176-83
pubmed: 22304731
Cell. 2018 May 31;173(6):1385-1397.e14
pubmed: 29706550
Bio Protoc. 2015 Jun 5;5(11):
pubmed: 27446979
Nature. 2020 Aug;584(7821):463-469
pubmed: 32717743
PLoS One. 2018 Aug 15;13(8):e0202049
pubmed: 30110400
Cell. 2020 May 28;181(5):1036-1045.e9
pubmed: 32416070
JAMA Intern Med. 2020 Jul 1;180(7):934-943
pubmed: 32167524
Antiviral Res. 2020 Jun;178:104791
pubmed: 32275914
Nat Immunol. 2018 Jun;19(6):625-635
pubmed: 29777224
Cell Host Microbe. 2020 Jun 10;27(6):992-1000.e3
pubmed: 32320677