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. Graphical abstract Unlabelled Image 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.
【저자키워드】 COVID-19, Monocytes, SARS-CoV-2, Pathogenesis, macrophages, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, ACE2, angiotensin-converting enzyme 2, TMPRSS2, Transmembrane serine protease 2, IFN, interferon, ARDS, acute respiratory distress syndrome, WHO, World Health Organization, CRP, C-reactive protein, PBMCs, peripheral blood mononuclear cells, PRRs, Pattern Recognition Receptors, NF-κB, nuclear factor-κB, ADAM17, ADAM metallopeptidase domain 17, MHC, major histocompatibility complex, CD, cluster of differentiation, PAMPs, pathogen-associated molecular patterns, ALI, Acute Lung Injury, siRNA, small interfering RNA, pDCs, plasmacytoid dendritic cells, IRF, Interferon regulatory factor, mTOR, Mammalian target of rapamycin, MCP-1, monocyte Chemoattractant Protein-1, RIG-I, Retinoic acid-inducible gene I, ADCC, antibody-dependent cellular cytotoxicity, MERS-CoV, Middle East respiratory syndrome-related coronavirus, CTL, cytotoxic T lymphocyte, NLRP3, nod-like receptor protein 3, Treg, regulatory T cells, MDA5, Melanoma differentiation-associated protein 5, PRRSV, porcine reproductive and respiratory syndrome virus, SARS-CoV, severe acute respiratory syndrome-related coronavirus, STAT, signal transducers and activators of transcription,