tetano
Editor, Senior Moderator
J Clin Immunol
. 2025 Oct 21;45(1):149.
doi: 10.1007/s10875-025-01943-6. Type I IFNs Decrease SARS-CoV-2 Replication in Human Cardiomyocytes and Increase Cytokine Production in Macrophages
Verónica Durán[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Eirini Nikolouli[SUP] #[/SUP][SUP] 4 [/SUP], Shambhabi Chatterjee[SUP] #[/SUP][SUP] 5 6 [/SUP], Bibiana Costa[SUP] 1 [/SUP], Andreas Pavlou[SUP] 1 [/SUP], Annett Ziegler[SUP] 1 [/SUP], Jennifer Becker[SUP] 1 [/SUP], Kira Baumann[SUP] 1 [/SUP], Matthias Bruhn[SUP] 1 [/SUP], Kathrin Haake[SUP] 7 [/SUP], Anna Rafiei Hashtchin[SUP] 7 [/SUP], Ingrid Gensch[SUP] 4 [/SUP], Andrea Korte[SUP] 5 [/SUP], Yvonne Lisa Behrens[SUP] 8 [/SUP], Shen-Ying Zhang[SUP] 9 10 11 [/SUP], Jean-Laurent Casanova[SUP] 9 10 11 12 13 [/SUP], Christian Bär[SUP] 5 6 [/SUP], Nico Lachmann[SUP] #[/SUP][SUP] 4 6 14 15 [/SUP], Thomas Thum[SUP] #[/SUP][SUP] 5 6 [/SUP], Ulrich Kalinke[SUP] #[/SUP][SUP] 16 17 [/SUP]
Affiliations
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[SUP]comp[/SUP]) and deficient (IFNAR1[SUP]def[/SUP]) 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[SUP]def[/SUP] than IFNAR1[SUP]comp[/SUP] cells. Treatment with exogenous IFNα mitigated infection in IFNAR1[SUP]comp[/SUP], but not in IFNAR1[SUP]def[/SUP] 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[SUP]def[/SUP] macrophages. In conclusion, type I IFNs decrease SARS-CoV-2 replication in human iPSC-derived cardiomyocytes, while they increase cytokine responses of macrophages.
. 2025 Oct 21;45(1):149.
doi: 10.1007/s10875-025-01943-6. Type I IFNs Decrease SARS-CoV-2 Replication in Human Cardiomyocytes and Increase Cytokine Production in Macrophages
Verónica Durán[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Eirini Nikolouli[SUP] #[/SUP][SUP] 4 [/SUP], Shambhabi Chatterjee[SUP] #[/SUP][SUP] 5 6 [/SUP], Bibiana Costa[SUP] 1 [/SUP], Andreas Pavlou[SUP] 1 [/SUP], Annett Ziegler[SUP] 1 [/SUP], Jennifer Becker[SUP] 1 [/SUP], Kira Baumann[SUP] 1 [/SUP], Matthias Bruhn[SUP] 1 [/SUP], Kathrin Haake[SUP] 7 [/SUP], Anna Rafiei Hashtchin[SUP] 7 [/SUP], Ingrid Gensch[SUP] 4 [/SUP], Andrea Korte[SUP] 5 [/SUP], Yvonne Lisa Behrens[SUP] 8 [/SUP], Shen-Ying Zhang[SUP] 9 10 11 [/SUP], Jean-Laurent Casanova[SUP] 9 10 11 12 13 [/SUP], Christian Bär[SUP] 5 6 [/SUP], Nico Lachmann[SUP] #[/SUP][SUP] 4 6 14 15 [/SUP], Thomas Thum[SUP] #[/SUP][SUP] 5 6 [/SUP], Ulrich Kalinke[SUP] #[/SUP][SUP] 16 17 [/SUP]
Affiliations
- PMID: 41117873
- PMCID: PMC12540622
- DOI: 10.1007/s10875-025-01943-6
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[SUP]comp[/SUP]) and deficient (IFNAR1[SUP]def[/SUP]) 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[SUP]def[/SUP] than IFNAR1[SUP]comp[/SUP] cells. Treatment with exogenous IFNα mitigated infection in IFNAR1[SUP]comp[/SUP], but not in IFNAR1[SUP]def[/SUP] 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[SUP]def[/SUP] macrophages. In conclusion, type I IFNs decrease SARS-CoV-2 replication in human iPSC-derived cardiomyocytes, while they increase cytokine responses of macrophages.