RT Journal Article
SR Electronic
T1 Primary macrophages exhibit a modest inflammatory response early in SARS-CoV-2 infection
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.02.02.478897
DO 10.1101/2022.02.02.478897
A1 Ziyun Zhang
A1 Rebecca Penn
A1 Wendy S Barclay
A1 Efstathios S Giotis
YR 2022
UL http://biorxiv.org/content/early/2022/02/04/2022.02.02.478897.abstract
AB 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 TCID50 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 infected 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 infection. Together, the findings concur that the hyperinflammation observed in SARS-CoV-2 infection is not driven by macrophages.Competing Interest StatementThe authors have declared no competing interest.COVID-19Coronavirus Disease 2019SARS-CoVSevere acute respiratory syndrome coronavirusTNFtumour necrosis factorILinterleukinIPInterferon gamma-induced proteinIFNinterferonHAhemagglutininNAneuraminidaseHPAIVhighly pathogenic avian influenza virusACE2angiotensin-converting Enzyme 2ANOVAanalysis of varianceGAPDHGlyceraldehyde 3-phosphate Dehydrogenase