Elsevier

Life Sciences

Volume 257, 15 September 2020, 118102
Life Sciences

Review article
Contribution of monocytes and macrophages to the local tissue inflammation and cytokine storm in COVID-19: Lessons from SARS and MERS, and potential therapeutic interventions

https://doi.org/10.1016/j.lfs.2020.118102Get rights and content

Highlights

  • A subset of monocytes and macrophages may be infected by SARS-CoV-2.

  • Coronavirus-infected monocyte can migrate to tissue and become infected macrophage.

  • Coronavirus-infected monocyte/macrophage produces high level of inflammatory factors.

  • Monocyte/macrophage-related cytokines promote organ inflammation and cytokine storm.

  • Local tissue inflammation and cytokine storm cause multi-organ failure in COVID-19.

Abstract

The COVID-19-, SARS- and MERS-related coronaviruses share many genomic and structural similarities. However, the SARS-CoV-2 is less pathogenic than SARS-CoV and MERS-CoV. Despite some differences in the cytokine patterns, it seems that the cytokine storm plays a crucial role in the pathogenesis of COVID-19-, SARS- and MERS. Monocytes and macrophages may be infected by SARS-CoV-2 through ACE2-dependent and ACE2-independent pathways. SARS-CoV-2 can effectively suppress the anti-viral IFN response in monocytes and macrophages. Since macrophages and dendritic cells (DCs) act as antigen presenting cells (APCs), the infection of these cells by SARS-CoV-2 impairs the adaptive immune responses against the virus. Upon infection, monocytes migrate to the tissues where they become infected resident macrophages, allowing viruses to spread through all organs and tissues. The SARS-CoV-2-infected monocytes and macrophages can produce large amounts of numerous types of pro-inflammatory cytokines and chemokines, which contribute to local tissue inflammation and a dangerous systemic inflammatory response called cytokine storm. Both local tissue inflammation and the cytokine storm play a fundamental role in the development of COVID-19-related complications, such as acute respiratory distress syndrome (ARDS), which is a main cause of death in COVID-19 patients. Here, we describe the monocytes and macrophage responses during severe coronavirus infections, while highlighting potential therapeutic interventions to attenuate macrophage-related inflammatory reactions in possible approaches for COVID-19 treatment.

Abbreviations

ADCC
antibody-dependent cellular cytotoxicity
ACE2
angiotensin-converting enzyme 2
ADAM17
ADAM metallopeptidase domain 17
ALI
acute lung injury
ARDS
acute respiratory distress syndrome
CD
cluster of differentiation
CRP
C-reactive protein
CTL
cytotoxic T lymphocyte
IFN
interferon
IRF
interferon regulatory factor
MCP-1
monocyte chemoattractant protein-1
MDA5
melanoma differentiation-associated protein 5
MERS-CoV
Middle East respiratory syndrome-related coronavirus
MHC
major histocompatibility complex
mTOR
mammalian target of rapamycin
NF-κB
nuclear factor-κB
NLRP3
Nod-like receptor protein 3
PAMPs
pathogen-associated molecular patterns
PBMCs
peripheral blood mononuclear cells
pDCs
plasmacytoid dendritic cells
PRRs
pattern recognition receptors
PRRSV
porcine reproductive and respiratory syndrome virus
RIG-I
retinoic acid-inducible gene I
SARS-CoV
severe acute respiratory syndrome-related coronavirus
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
siRNA
small interfering RNA
STAT
signal transducers and activators of transcription
TMPRSS2
transmembrane serine protease 2
Treg
regulatory T cells
WHO
World Health Organization

Keywords

COVID-19
SARS-CoV-2
Macrophages
Monocytes
Pathogenesis

Cited by (0)

View Abstract