Type I IFNs Decrease SARS-CoV-2 Replication in Human Cardiomyocytes and Increase Cytokine Production in Macrophages
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.
Authors
- Arthur Korte (ORCID: https://orcid.org/0000-0003-0831-1463)
- Ulrich Kalinke (ORCID: https://orcid.org/0000-0003-0503-9564)
- Thomas Thum (ORCID: https://orcid.org/0000-0003-4360-1511)
- Shambhabi Chatterjee (ORCID: https://orcid.org/0000-0001-5978-3562)
- Yvonne Lisa Behrens (ORCID: https://orcid.org/0000-0002-2390-0541)
- Nico Lachmann (ORCID: https://orcid.org/0000-0002-4245-1497)
- Jean‐Laurent Casanova (ORCID: https://orcid.org/0000-0002-7782-4169)
- Bibiana Costa
- Anna Rafiei Hashtchin (ORCID: https://orcid.org/0000-0002-6917-2519)
- Kathrin Haake (ORCID: https://orcid.org/0000-0002-3713-2694)
- Matthias Bruhn (ORCID: https://orcid.org/0009-0008-2748-4080)
- Verónica Durán (ORCID: https://orcid.org/0000-0003-3231-4058)
- Eirini Nikolouli
- Shen‐Ying Zhang (ORCID: https://orcid.org/0000-0002-9449-3672)
- Andreas Pavlou (ORCID: https://orcid.org/0000-0002-0435-459X)
- Kira Baumann
- Annett Ziegler (ORCID: https://orcid.org/0000-0002-2033-5049)
- Ingrid Gensch
- Christian v. Bar (ORCID: https://orcid.org/0000-0002-1239-5105)
- Stephan Becker (ORCID: https://orcid.org/0000-0002-0122-3922)
Institutions
- Howard Hughes Medical Institute (US)
- Inserm (FR)
- Medizinische Hochschule Hannover (DE)
- Assistance Publique – Hôpitaux de Paris (FR)
- Fraunhofer Institute for Toxicology and Experimental Medicine (DE)
- Chan Zuckerberg Initiative (United States) (US)
- Helmholtz Centre for Infection Research (DE)
- Center for Experimental and Clinical Infection Research (DE)
- Institut des Maladies Génétiques Imagine (FR)
- Rockefeller University (US)
- Stanford University (US)
Publication Details
- Journal
- Journal of Clinical Immunology
- Published
- 2025-10-21
- DOI
- https://doi.org/10.1007/s10875-025-01943-6
- Citations
- 1
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 1.40