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.
【저자키워드】 SARS-CoV-2, Inflammation, proteomics, Cytokine storm, macrophages, transcriptomics, interferon, end-organ disease, 【초록키워드】 COVID-19, coronavirus disease, Monocytes, Macrophage, Respiratory distress syndrome, viral infection, Coronavirus disease 2019, ARDS, coronavirus, innate immune response, macrophages, acute respiratory distress syndrome, Infection, cytokine, severe acute respiratory syndrome Coronavirus, angiotensin-converting enzyme 2, dendritic cells, chemokine, immune, type I interferon, SARS-CoV-2 receptor, activity, Viral, viral replication, IFN, systemic inflammation, receptor, respiratory, expression, signaling pathways, proteomic, Angiotensin-converting enzyme, acute respiratory distress, Evidence, innate immune, Interaction, angiotensin, Inflammatory, human monocyte-derived macrophages, evidence of, dysregulation, respiratory distress, acute respiratory syndrome, Activation, acute respiratory syndrome coronavirus, tissue damage, acute respiratory syndrome coronavirus 2, profile, life-threatening coronavirus disease, morbidities, syndrome, pro-inflammatory cytokine, component, virion, virions, human monocyte, while, pro-inflammatory, Host, Affect, transcriptomic, mononuclear phagocytes, malfunctions, robust, investigated, characterized, monocyte-macrophage, affecting, end-organ, mononuclear phagocyte, the SARS-CoV-2, 【제목키워드】 response, Innate,