Type I IFNs Decrease SARS-CoV-2 Replication in Human Cardiomyocytes and Increase Cytokine Production in Macrophages
Durán V, Nikolouli E, Chatterjee S, Costa B, Pavlou A, Ziegler A, Becker J, Baumann K, Bruhn M, Haake K, Hashtchin A, Gensch I, Korte A, Behrens Y, Zhang S, Casanova J, Bär C, Lachmann N, Thum T, Kalinke U
Published in
Journal of Clinical Immunology: Volume 45, Issue 1, Page 149
Abstract
The cellular basis of COVID-19 severity in patients with deficiencies in type I IFN immunity remains unclear. In this study, we differentiated cardiomyocytes and macrophages from IFNAR1 competent (IFNAR1(comp)) and deficient (IFNAR1(def)) induced pluripotent stem cells (iPSCs), and analyzed virus replication and cytokine production after exposure to SARS-CoV-2. Cardiomyocytes expressed the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) and showed abundant SARS-CoV-2 replication, which was higher in IFNAR1(def) than IFNAR1(comp) cells. Treatment with exogenous IFNα mitigated infection in IFNAR1(comp), but not in IFNAR1(def) cardiomyocytes. In contrast, macrophages did not express ACE2 and did not support SARS-CoV-2 replication, but produced pro-inflammatory cytokines upon virus exposure, which was impaired in IFNAR1(def) macrophages. In conclusion, type I IFNs decrease SARS-CoV-2 replication in human iPSC-derived cardiomyocytes, while they increase cytokine responses of macrophages.
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