Defining the Innate Immune Responses for SARS-CoV-2-Human Macrophage Interactions.
Angiotensin-Converting Enzyme 2
/ genetics
COVID-19
/ immunology
Cells, Cultured
Cytokines
/ genetics
Gene Expression Profiling
Gene Regulatory Networks
Host-Pathogen Interactions
Humans
Immunity, Innate
/ genetics
Inflammation Mediators
/ metabolism
Macrophages
/ immunology
Proteome
Proteomics
Receptors, Virus
/ genetics
SARS-CoV-2
/ immunology
Signal Transduction
Transcriptome
SARS-CoV-2
cytokine storm
end-organ disease
inflammation
interferon
macrophages
proteomics
transcriptomics
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
14
07
2021
accepted:
15
09
2021
entrez:
21
10
2021
pubmed:
22
10
2021
medline:
30
10
2021
Statut:
epublish
Résumé
Host innate immune response follows severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and it is the driver of the acute respiratory distress syndrome (ARDS) amongst other inflammatory end-organ morbidities. Such life-threatening coronavirus disease 2019 (COVID-19) is heralded by virus-induced activation of mononuclear phagocytes (MPs; monocytes, macrophages, and dendritic cells). MPs play substantial roles in aberrant immune secretory activities affecting profound systemic inflammation and end-organ malfunctions. All follow the presence of persistent viral components and virions without evidence of viral replication. To elucidate SARS-CoV-2-MP interactions we investigated transcriptomic and proteomic profiles of human monocyte-derived macrophages. While expression of the SARS-CoV-2 receptor, the angiotensin-converting enzyme 2, paralleled monocyte-macrophage differentiation, it failed to affect productive viral infection. In contrast, simple macrophage viral exposure led to robust pro-inflammatory cytokine and chemokine expression but attenuated type I interferon (IFN) activity. Both paralleled dysregulation of innate immune signaling pathways, specifically those linked to IFN. We conclude that the SARS-CoV-2-infected host mounts a robust innate immune response characterized by a pro-inflammatory storm heralding end-organ tissue damage.
Identifiants
pubmed: 34671355
doi: 10.3389/fimmu.2021.741502
pmc: PMC8521106
doi:
Substances chimiques
Cytokines
0
Inflammation Mediators
0
Proteome
0
Receptors, Virus
0
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Banques de données
figshare
['10.6084/m9.figshare.16550286.v1']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
741502Subventions
Organisme : NINDS NIH HHS
ID : R01 NS036126
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103427
Pays : United States
Organisme : NIDA NIH HHS
ID : P01 DA028555
Pays : United States
Organisme : NIMH NIH HHS
ID : P30 MH062261
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM113126
Pays : United States
Organisme : NIMH NIH HHS
ID : P01 MH064570
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG043540
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS034239
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
Copyright © 2021 Abdelmoaty, Yeapuri, Machhi, Olson, Shahjin, Kumar, Zhou, Liang, Pandey, Acharya, Byrareddy, Mosley and Gendelman.
Déclaration de conflit d'intérêts
Author HEG is a co-founder of Exavir Therapeutics, Inc. who is developing antiviral and elimination therapies for HIV/AIDS and other viral infections. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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