Involvement of macrophages in the SARS-CoV-2-associated cytokine storm, the excessive secretion of inflammatory/anti-viral factors leading to the acute respiratory distress syndrome (ARDS) in COVID-19 patients, is unclear. In this study, we sought to characterize the interplay between the virus and primary human monocyte-derived macrophages (MDM). MDM were stimulated with recombinant IFN-α and/or infected with either live or UV-inactivated SARS-CoV-2 or with two reassortant influenza viruses containing external genes from the H1N1 PR8 strain and heterologous internal genes from a highly pathogenic avian H5N1 or a low pathogenic human seasonal H1N1 strain. Virus replication was monitored by qRT-PCR for the E viral gene for SARS-CoV-2 or M gene for influenza and TCID 50 or plaque assay, and cytokine levels were assessed semiquantitatively with qRT-PCR and a proteome cytokine array. We report that MDM are not susceptible to SARS-CoV-2 whereas both influenza viruses replicated in MDM, albeit abortively. We observed a modest cytokine response in SARS-CoV-2 exposed MDM with notable absence of IFN-β induction, which was instead strongly induced by the influenza viruses. Pre-treatment of MDM with IFN-α enhanced proinflammatory cytokine expression upon exposure to virus. Together, the findings concur that the hyperinflammation observed in SARS-CoV-2 infection is not driven by macrophages.
【저자키워드】 SARS-CoV-2, Cytokines, macrophages, Influenza, Infectivity, 【초록키워드】 Macrophage, ARDS, Cytokine storm, SARS-COV-2 infection, qRT-PCR, cytokine, Influenza virus, virus, Replication, hyperinflammation, influenza viruses, H1N1, proteome, expression, COVID-19 patients, Heterologous, acute respiratory distress, Plaque assay, cytokine response, IFN-α, Proinflammatory cytokine, Factor, IFN-β, syndrome, pathogenic, H5N1, TCID, excessive secretion, highly pathogenic, M gene, susceptible, stimulated, absence, replicated, notable, driven by, Involvement, cytokine level, external gene, human monocyte-derived macrophage, MDM, semiquantitatively, were assessed, 【제목키워드】 Human, response, refractory,