Abstract
Immune cells of the monocyte/macrophage lineage are characterized by their diversity, plasticity, and variety of functions. Among them, macrophages play a central role in antiviral responses, tissue repair, and fibrosis. Macrophages can be reprogrammed by environmental cues, thus changing their phenotype during an antiviral immune response as the viral infection progresses. While M1-like macrophages are essential for the initial inflammatory responses, M2-like macrophages are critical for tissue repair after pathogen clearance. Numerous reports have evaluated the detrimental effects that coronaviruses, e.g., HCoV-229E, SARS-CoV, MERS-CoV, and SARS-CoV-2, have on the antiviral immune response and macrophage functions. In this review, we have addressed the breadth of macrophage phenotypes during the antiviral response and provided an overview of macrophage-coronavirus interactions. We also discussed therapeutic approaches to target macrophage-induced complications, currently under evaluation in clinical trials for coronavirus disease 2019 patients. Additionally, we have proposed alternative approaches that target macrophage recruitment, interferon signaling, cytokine storm, pulmonary fibrosis, and hypercoagulability.
Highlights
Macrophages play multiple roles in the innate immune system
This may lead to the development of the life-threatening conditions that are observed in severely ill COVID-19 patients like cytokine storm and pulmonary fibrosis (Jose and Manuel, 2020; Yuen et al, 2020; Mehta P. et al, 2020; Xu Y.-H. et al, 2020), as these processes are tightly regulated by macrophages
In two severe cases of COVID-19, lung injuries and cavities were filled with macrophages and neutrophils, where a fibrinous exudate could be detected, along with IL-6, TNFα, and PD-L1 and a decrease in lymphocytes (Wang et al, 2020). These results suggest that increased infiltration of macrophages in the lungs might be responsible for the cytokine storm and pulmonary fibrosis observed in severe cases of COVID-19
Summary
Macrophages play multiple roles in the innate immune system. They can phagocytose bacteria and viruses to trigger an immune response, as well as promote tissue homeostasis and regeneration (Gordon and Taylor, 2005). Multiple reports on SARS-CoV-2 and macrophage interactions that are discussed in this review have not been peer-reviewed yet, they suggest that CoVs can negatively affect and diminish macrophage function during the antiviral response This may lead to the development of the life-threatening conditions that are observed in severely ill COVID-19 patients like cytokine storm and pulmonary fibrosis (Jose and Manuel, 2020; Yuen et al, 2020; Mehta P. et al, 2020; Xu Y.-H. et al, 2020), as these processes are tightly regulated by macrophages. Modulating macrophage function and recruitment during the CoV infection process is a potential therapeutic approach to improve the antiviral immune response and decrease the life-threatening conditions observed in severe cases. We summarize ongoing clinical trials for COVID-19 patients that target macrophage function, as well as propose alternative approaches
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