Abstract
Host innate immune response follows severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and it is the driver of the acute respiratory distress syndrome (ARDS) amongst other inflammatory end-organ morbidities. Such life-threatening coronavirus disease 2019 (COVID-19) is heralded by virus-induced activation of mononuclear phagocytes (MPs; monocytes, macrophages, and dendritic cells). MPs play substantial roles in aberrant immune secretory activities affecting profound systemic inflammation and end-organ malfunctions. All follow the presence of persistent viral components and virions without evidence of viral replication. To elucidate SARS-CoV-2-MP interactions we investigated transcriptomic and proteomic profiles of human monocyte-derived macrophages. While expression of the SARS-CoV-2 receptor, the angiotensin-converting enzyme 2, paralleled monocyte-macrophage differentiation, it failed to affect productive viral infection. In contrast, simple macrophage viral exposure led to robust pro-inflammatory cytokine and chemokine expression but attenuated type I interferon (IFN) activity. Both paralleled dysregulation of innate immune signaling pathways, specifically those linked to IFN. We conclude that the SARS-CoV-2-infected host mounts a robust innate immune response characterized by a pro-inflammatory storm heralding end-organ tissue damage.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is an enveloped positive-stranded RNA virus belonging to the Coronaviridae family, Betacoronaviruses genus [1]
angiotensin-converting enzyme 2 (ACE2) expression by monocytes was found to peak by day 5 after initiation of cell differentiation decreased after that (Figure 1A), which corresponds to the susceptibility of infection of monocytes-macrophages by other viruses [20, 36, 37]
The number of genome copies did not change significantly with or without captopril. These results demonstrated that SARS-CoV-2 infection of human monocyte-derived macrophages (MDMs) was restrictive without evidence of viral replication and differentiated monocytes could not generate progeny virus in contrast to productive infection of SARS-CoV-2 in Vero.Signal Transducer and Activator of Transcription 1 (STAT1) KO cells (Figure 1B)
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is an enveloped positive-stranded RNA virus belonging to the Coronaviridae family, Betacoronaviruses genus [1]. COVID-19 ranges from asymptomatic infection to mild pneumonia and, in its most severe form, progression to acute respiratory distress syndrome (ARDS). Such pulmonary compromise is associated with dyspnea and hypoxia that can progress to severely compromised lung dysfunction and multiorgan system failure and death [3]. Nearly 15% of reported COVID-19 disease cases progress to ARDS defined by widespread inflammatory-associated lung tissue damage and multiorgan failure [5] involving heart, liver, gastrointestinal tract, kidney, and brain [6]. Viral persistence in the face of such end-organ disease is linked to cell expression of angiotensin-converting enzyme 2 (ACE2), the molecule that SARS-CoV-2 utilizes for receptor-mediated cell entry [7]
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