Influenza hijacks myeloid cells to inflict type-I interferon-fueled damage in the heart.

Summary

Influenza infects CCR2+ circulating pro-DC3 myeloid cells that home to the CCL2-rich heart, transfer virus to cardiomyocytes, and trigger IFNAR1-dependent injury. Cardiomyocyte-specific dampening of IFNAR1 signaling protects the heart without compromising pulmonary antiviral immunity.

Key Findings

• CCR2-high circulating pro-DC3 myeloid cells become infected after pulmonary influenza and preferentially home to the CCL2-rich heart.
• Virus escapes pro-DC3 within the myocardium to infect cardiomyocytes and induce type-I interferon production.
• IFNAR1 activation on cardiomyocytes drives tissue damage and impaired function; cardiomyocyte-specific IFNAR1 dampening protects the heart while preserving lung antiviral immunity.

Clinical Implications

During influenza seasons, patients at cardiovascular risk may benefit from strategies that modulate IFN-I signaling in the heart; future therapies could aim for cell-specific IFNAR1 blockade to prevent myocarditis-like injury without blunting systemic antiviral defense.

Limitations

• Predominantly preclinical; human causal confirmation and safety of cardiomyocyte-specific IFNAR1 modulation are pending
• Translational biomarkers for patient selection were not established

Future Directions

Develop cardiomyocyte-targeted IFNAR1 modulators, define safety windows, and identify biomarkers to stratify patients at risk for influenza-related cardiac injury for clinical trials.