tetano
Editor, Senior Moderator
Immunity
. 2026 Feb 9:S1074-7613(25)00567-9.
doi: 10.1016/j.immuni.2025.12.011. Online ahead of print.
Influenza hijacks myeloid cells to inflict type-I interferon-fueled damage in the heart
Jeffrey Downey[SUP] 1 [/SUP], Ana Oliveira-Coelho[SUP] 1 [/SUP], Máté G Kiss[SUP] 1 [/SUP], Gabriel Laghlali[SUP] 2 [/SUP], Alexander Leunig[SUP] 1 [/SUP], Emir Radkevich[SUP] 3 [/SUP], Laszlo Halasz[SUP] 3 [/SUP], Martin Umali[SUP] 4 [/SUP], Joana Ferreira da Silva[SUP] 5 [/SUP], Madeline L Eller[SUP] 6 [/SUP], Matteo Gianeselli[SUP] 1 [/SUP], Magdalena M Żak[SUP] 1 [/SUP], Haley E Randolph[SUP] 7 [/SUP], Gabriel Caumartin[SUP] 1 [/SUP], Wolfram C Poller[SUP] 1 [/SUP], Henrike Janssen[SUP] 1 [/SUP], Laura L Koekkoek[SUP] 1 [/SUP], Jamshid Abdul-Ghafar[SUP] 8 [/SUP], Pacific Huynh[SUP] 1 [/SUP], Darwin D'Souza[SUP] 9 [/SUP], Vladimir Roudko[SUP] 3 [/SUP], Sheqouia Nauta[SUP] 10 [/SUP], Jazz Munitz[SUP] 10 [/SUP], Xisheng Li[SUP] 1 [/SUP], Thomas Rathner[SUP] 1 [/SUP], Ziche Chen[SUP] 1 [/SUP], Anh Phan[SUP] 1 [/SUP], Abigail Glick[SUP] 1 [/SUP], Katarzyna Cialowicz[SUP] 11 [/SUP], Zhihong Chen[SUP] 9 [/SUP], Seunghee Kim-Schulze[SUP] 12 [/SUP], Seonghun Yoon[SUP] 1 [/SUP], Matthias Nahrendorf[SUP] 13 [/SUP], Susmita Sahoo[SUP] 1 [/SUP], Miriam Merad[SUP] 14 [/SUP], Adolfo García-Sastre[SUP] 15 [/SUP], Cameron S McAlpine[SUP] 1 [/SUP], Gustav J Strijkers[SUP] 16 [/SUP], Viviana Simon[SUP] 17 [/SUP], Rachel Brody[SUP] 8 [/SUP], Saurabh Mehandru[SUP] 18 [/SUP], Zahi A Fayad[SUP] 4 [/SUP], Benjamin P Kleinstiver[SUP] 5 [/SUP], Lior Zangi[SUP] 1 [/SUP], Mandy M T van Leent[SUP] 10 [/SUP], Michael Schotsaert[SUP] 19 [/SUP], Filip K Swirski[SUP] 20 [/SUP]
Affiliations
Abundant evidence has correlated influenza infection with cardiovascular disease, yet mechanisms linking infection with the heart remain poorly understood. Here, we show that influenza infection damaged the human and murine heart. In mice, we showed that shortly after pulmonary infection, the virus infected a circulating myeloid pro-dendritic cell 3 (pro-DC3) that expressed high concentrations of the chemokine receptor CCR2. The heart, which produces abundant CCL2, preferentially attracted infected pro-DC3. In the myocardium, the virus escaped pro-DC3, infected cardiomyocytes, and triggered production of type-I interferon (IFN-I). Engagement of the IFN-I receptor (IFNAR1) on cardiomyocytes caused tissue damage and compromised heart function. Genetically and therapeutically dampening IFNAR1 exclusively in cardiomyocytes protected the heart while preserving anti-viral immunity in the lung. Our results identify a series of host-pathogen interactions that propagate tissue damage and uncover an axis for intervention to mitigate cardiovascular risk following viral infection.
Keywords: cardiovascular disease; heart; influenza; myeloid cells; pro-DC3; type I interferon.
. 2026 Feb 9:S1074-7613(25)00567-9.
doi: 10.1016/j.immuni.2025.12.011. Online ahead of print.
Influenza hijacks myeloid cells to inflict type-I interferon-fueled damage in the heart
Jeffrey Downey[SUP] 1 [/SUP], Ana Oliveira-Coelho[SUP] 1 [/SUP], Máté G Kiss[SUP] 1 [/SUP], Gabriel Laghlali[SUP] 2 [/SUP], Alexander Leunig[SUP] 1 [/SUP], Emir Radkevich[SUP] 3 [/SUP], Laszlo Halasz[SUP] 3 [/SUP], Martin Umali[SUP] 4 [/SUP], Joana Ferreira da Silva[SUP] 5 [/SUP], Madeline L Eller[SUP] 6 [/SUP], Matteo Gianeselli[SUP] 1 [/SUP], Magdalena M Żak[SUP] 1 [/SUP], Haley E Randolph[SUP] 7 [/SUP], Gabriel Caumartin[SUP] 1 [/SUP], Wolfram C Poller[SUP] 1 [/SUP], Henrike Janssen[SUP] 1 [/SUP], Laura L Koekkoek[SUP] 1 [/SUP], Jamshid Abdul-Ghafar[SUP] 8 [/SUP], Pacific Huynh[SUP] 1 [/SUP], Darwin D'Souza[SUP] 9 [/SUP], Vladimir Roudko[SUP] 3 [/SUP], Sheqouia Nauta[SUP] 10 [/SUP], Jazz Munitz[SUP] 10 [/SUP], Xisheng Li[SUP] 1 [/SUP], Thomas Rathner[SUP] 1 [/SUP], Ziche Chen[SUP] 1 [/SUP], Anh Phan[SUP] 1 [/SUP], Abigail Glick[SUP] 1 [/SUP], Katarzyna Cialowicz[SUP] 11 [/SUP], Zhihong Chen[SUP] 9 [/SUP], Seunghee Kim-Schulze[SUP] 12 [/SUP], Seonghun Yoon[SUP] 1 [/SUP], Matthias Nahrendorf[SUP] 13 [/SUP], Susmita Sahoo[SUP] 1 [/SUP], Miriam Merad[SUP] 14 [/SUP], Adolfo García-Sastre[SUP] 15 [/SUP], Cameron S McAlpine[SUP] 1 [/SUP], Gustav J Strijkers[SUP] 16 [/SUP], Viviana Simon[SUP] 17 [/SUP], Rachel Brody[SUP] 8 [/SUP], Saurabh Mehandru[SUP] 18 [/SUP], Zahi A Fayad[SUP] 4 [/SUP], Benjamin P Kleinstiver[SUP] 5 [/SUP], Lior Zangi[SUP] 1 [/SUP], Mandy M T van Leent[SUP] 10 [/SUP], Michael Schotsaert[SUP] 19 [/SUP], Filip K Swirski[SUP] 20 [/SUP]
Affiliations
- PMID: 41666933
- DOI: 10.1016/j.immuni.2025.12.011
Abundant evidence has correlated influenza infection with cardiovascular disease, yet mechanisms linking infection with the heart remain poorly understood. Here, we show that influenza infection damaged the human and murine heart. In mice, we showed that shortly after pulmonary infection, the virus infected a circulating myeloid pro-dendritic cell 3 (pro-DC3) that expressed high concentrations of the chemokine receptor CCR2. The heart, which produces abundant CCL2, preferentially attracted infected pro-DC3. In the myocardium, the virus escaped pro-DC3, infected cardiomyocytes, and triggered production of type-I interferon (IFN-I). Engagement of the IFN-I receptor (IFNAR1) on cardiomyocytes caused tissue damage and compromised heart function. Genetically and therapeutically dampening IFNAR1 exclusively in cardiomyocytes protected the heart while preserving anti-viral immunity in the lung. Our results identify a series of host-pathogen interactions that propagate tissue damage and uncover an axis for intervention to mitigate cardiovascular risk following viral infection.
Keywords: cardiovascular disease; heart; influenza; myeloid cells; pro-DC3; type I interferon.