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

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

doi:10.1093/infdis/jiaa753

Cited by 147 publications

(172 citation statements)

References 42 publications

(55 reference statements)

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“…However, production of these cytokines was generally lower in comparison to SARS-CoV-2 monocyte-derived macrophage. Unlike earlier observations, this study observed minimal up-regulation of IP-10 [34]. Thus, in contrast to SARS-CoV-1, in vitro infections of DC show conflicting support for the idea that DCs act as a significant source of proinflammatory cytokines and point toward other cell types that may be contributors of the cytokine storms observed in severe COVID-19.…”

Section: And Innate Immunity To Covid-19contrasting

confidence: 99%

“…While cDC and pDC express little to no ACE2 [33], moDC have recently been shown to express ACE2, albeit less than Calu3 cells [27]. SARS-CoV-2 has been demonstrated to infect moDC, but the infection is abortive [27,34]. In addition to ACE2, SARS-CoV-2 may infect various DC subsets through interaction with CD147, another receptor which binds SARS-CoV-2.…”

Section: And Innate Immunity To Covid-19mentioning

confidence: 99%

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A Missing Link: Engagements of Dendritic Cells in the Pathogenesis of SARS-CoV-2 Infections

Fisk

Upreti

Kung

2021

IJMS

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Dendritic cells (DC) connect the innate and adaptive arms of the immune system and carry out numerous roles that are significant in the context of viral disease. Their functions include the control of inflammatory responses, the promotion of tolerance, cross-presentation, immune cell recruitment and the production of antiviral cytokines. Based primarily on the available literature that characterizes the behaviour of many DC subsets during Severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19), we speculated possible mechanisms through which DC could contribute to COVID-19 immune responses, such as dissemination of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to lymph nodes, mounting dysfunctional inteferon responses and T cell immunity in patients. We highlighted gaps of knowledge in our understanding of DC in COVID-19 pathogenesis and discussed current pre-clinical development of therapies for COVID-19.

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Section: And Innate Immunity To Covid-19contrasting

confidence: 99%

Section: And Innate Immunity To Covid-19mentioning

confidence: 99%

A Missing Link: Engagements of Dendritic Cells in the Pathogenesis of SARS-CoV-2 Infections

Fisk

Upreti

Kung

2021

IJMS

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“…While writing the present manuscript contradictory data were published claiming that SARS-CoV-2 induces an immune activation of hMDM (Zheng et al, 2020). These conflicting results might be the consequence of different methodologies used.…”

Section: Discussionmentioning

confidence: 77%

“…These conflicting results might be the consequence of different methodologies used. While we employed purified monocytes to generate macrophages in six days, Zheng and collaborators kept PBMC with M-CSF for four days and then for another 10 days when the cells became adherent (Zheng et al, 2020). Another important methodological difference is that our study used ELISA to detect cytokines while Zheng and collaborators analyzed mRNA by RT-PCR.…”

Section: Discussionmentioning

confidence: 99%

No Evidence for Human Monocyte-Derived Macrophage Infection and Antibody-Mediated Enhancement of SARS-CoV-2 Infection

García-Nicolás

V’kovski

Zettl³

et al. 2021

Front. Cell. Infect. Microbiol.

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Vaccines are essential to control the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and to protect the vulnerable population. However, one safety concern of vaccination is the possible development of antibody-dependent enhancement (ADE) of SARS-CoV-2 infection. The potential infection of Fc receptor bearing cells such as macrophages, would support continued virus replication and inflammatory responses, and thereby potentially worsen the clinical outcome of COVID-19. Here we demonstrate that SARS-CoV-2 and SARS-CoV neither infect human monocyte-derived macrophages (hMDM) nor induce inflammatory cytokines in these cells, in sharp contrast to Middle East respiratory syndrome (MERS) coronavirus and the common cold human coronavirus 229E. Furthermore, serum from convalescent COVID-19 patients neither induced enhancement of SARS-CoV-2 infection nor innate immune response in hMDM. Although, hMDM expressed angiotensin-converting enzyme 2, no or very low levels of transmembrane protease serine 2 were found. These results support the view that ADE may not be involved in the immunopathological processes associated with COVID-19, however, more studies are necessary to understand the potential contribution of antibodies-virus complexes with other cells expressing FcR receptors.

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“…By contrast, the systematic down-regulation of genes encoding MHC class II molecules is more likely explained by a direct interaction of cDCs with the virus. This prediction was also supported by evidence that the virus can infect monocyte derived DCs ( 28 ).…”

Section: Main Textmentioning

confidence: 62%

Maturation signatures of conventional dendritic cell subtypes in COVID-19 reflect direct viral sensing

Marongiu

Protti

et al. 2021

Preprint

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Growing evidence suggests that conventional dendritic cells (cDCs) undergo aberrant maturation in COVID-19, and this adversely affects T cell activation. Here, we find that cDC2 subtypes show similar infection-induced gene signatures with an increasing gradient of expression of interferon-stimulated genes from mild to severe patients and a down-regulation of major histocompatibility complex class II (MHC class II) molecules and some inflammatory cytokines compared to the baseline level of healthy donors. In vitro, the direct exposure of cDC2s to the virus recapitulates the type of activation observed in vivo. Our findings provide evidence that SARS-CoV-2 can directly interact with cDC2s and, by down-regulating crucial molecules required for T cell activation, implements an efficient immune escape mechanism.

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

Cited by 147 publications

References 42 publications

A Missing Link: Engagements of Dendritic Cells in the Pathogenesis of SARS-CoV-2 Infections

A Missing Link: Engagements of Dendritic Cells in the Pathogenesis of SARS-CoV-2 Infections

No Evidence for Human Monocyte-Derived Macrophage Infection and Antibody-Mediated Enhancement of SARS-CoV-2 Infection

Maturation signatures of conventional dendritic cell subtypes in COVID-19 reflect direct viral sensing

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