Severe Acute Respiratory Syndrome Coronavirus 2-Induced Immune Activation and Death of Monocyte-Derived Human Macrophages and Dendritic Cells

Jian Zheng; Yuhang Wang; Kun Li; David K Meyerholz; Chantal Allamargot; Stanley Perlman

doi:10.1093/infdis/jiaa753

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Severe Acute Respiratory Syndrome Coronavirus 2-Induced Immune Activation and Death of Monocyte-Derived Human Macrophages and Dendritic Cells

Journal article

Open access

Peer reviewed

Severe Acute Respiratory Syndrome Coronavirus 2-Induced Immune Activation and Death of Monocyte-Derived Human Macrophages and Dendritic Cells

Jian Zheng, Yuhang Wang, Kun Li, David K Meyerholz, Chantal Allamargot and Stanley Perlman

The Journal of infectious diseases, Vol.223(5), pp.785-795

03/03/2021

DOI: 10.1093/infdis/jiaa753

PMCID: PMC7799009

PMID: 33277988

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Abstract

Studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients and experimentally infected animals indicate a critical role for augmented expression of proinflammatory chemokines and cytokines in severe disease. Here, we demonstrate that SARS-CoV-2 infection of human monocyte-derived macrophages (MDMs) and monocyte-derived dendritic cells was abortive, but induced the production of multiple antiviral and proinflammatory cytokines (interferon-α, interferon-β, tumor necrosis factor, and interleukins 1β, 6, and 10) and a chemokine (CXCL10). Despite the lack of efficient replication in MDMs, SARS-CoV-2 induced profound interferon-mediated cell death of host cells. Macrophage activation and death were not enhanced by exposure to low levels of convalescent plasma, suggesting that antibody-dependent enhancement of infection does not contribute to cell death. Together, these results indicate that infection of macrophages and dendritic cells potentially plays a major role in coronavirus disease 2019 pathogenesis, even in the absence of productive infection.

COVID-19 - immunology

Macrophages - ultrastructure

Microscopy, Electron, Transmission

Cytokines - metabolism

Dendritic Cells - immunology

Humans

RNA, Messenger - metabolism

Chemokines - genetics

Leukocytes, Mononuclear - virology

COVID-19 - therapy

Macrophages - virology

Dendritic Cells - ultrastructure

Leukocytes, Mononuclear - immunology

Cell Death

Immunization, Passive

SARS-CoV-2 - immunology

Chemokines - metabolism

RNA, Viral - metabolism

Dendritic Cells - virology

Cytokines - genetics

Macrophages - immunology

Details

Title: Subtitle: Severe Acute Respiratory Syndrome Coronavirus 2-Induced Immune Activation and Death of Monocyte-Derived Human Macrophages and Dendritic Cells
Creators: Jian Zheng - Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA
Yuhang Wang - Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa, USA
Kun Li - Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA
David K Meyerholz - Department of Pathology, University of Iowa, Iowa City, Iowa, USA
Chantal Allamargot - Central Microscopy Research Facility, University of Iowa, Iowa City, Iowa, USA
Stanley Perlman - Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: The Journal of infectious diseases, Vol.223(5), pp.785-795
DOI: 10.1093/infdis/jiaa753
PMID: 33277988
PMCID: PMC7799009
NLM abbreviation: J Infect Dis
ISSN: 0022-1899
eISSN: 1537-6613
Publisher: United States
Grant note: P01 AI060699 / NIAID NIH HHS R01 AI129269 / NIAID NIH HHS
Language: English
Date published: 03/03/2021
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Core Research Facilities; Pathology; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9984070129702771

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