Mount Sinai investigators have uncovered a critical molecular interplay linking severe influenza A virus (IAV) infections to acute cardiovascular complications, elucidating long-standing clinical observations that flu seasons correlate with increased incidence of heart attacks and related events. Their groundbreaking study delineates how influenza exploits a defined subset of immune cells, initiating a deleterious type I interferon (IFN-I) cascade within cardiac tissue, precipitating damage to the myocardium. These findings, recently published in the journal Immunity, bear significant implications for the development of targeted therapeutics aimed at mitigating virus-induced cardiac injury while preserving essential antiviral immunity.
While influenza viruses are primarily respiratory pathogens, their systemic impacts, particularly on the heart, have been clinically recognized but mechanistically elusive. The Mount Sinai team employed sophisticated mouse models alongside comprehensive analysis of human autopsy specimens from patients succumbing to influenza. Intriguingly, their data revealed that over 85% of these patients harbored preexisting cardiovascular comorbidities, including hypertension, atherosclerosis, and cardiac fibrosis, signifying a heightened vulnerability to influenza-mediated cardiac insults.
Central to the team’s discovery is the role of a previously uncharacterized myeloid cell population, designated pro-dendritic cell 3 (pDC3). This immune cell subset exhibits a unique susceptibility to IAV infection within the pulmonary microenvironment. Subsequent trafficking of pDC3 cells from the lungs to the myocardium facilitates viral dissemination directly into cardiac tissues. In response to this localized viral presence, pDC3 cells vigorously produce type I interferons, potent antiviral cytokines intended to orchestrate viral clearance. Paradoxically, this IFN-I response proves maladaptive in the heart, inducing apoptosis of cardiomyocytes, the contractile cells imperative for cardiac output, thus compromising cardiac function.
This “Trojan horse” mechanism, wherein pDC3 cells act as vectors transporting virus into the heart, represents a novel paradigm in influenza pathology. Such cellular infiltration triggers an inflammatory milieu that not only impairs myocardial cell viability but also exacerbates preexisting cardiac disease states, thereby escalating morbidity and mortality risks during influenza outbreaks. Detailed histopathological analyses of patient samples and experimental infection models confirmed elevated troponin levels, a biomarker of myocardial injury, and diminished left ventricular ejection fraction (LVEF), underscoring functional cardiac impairments associated with this pathway.
Building upon these insights, the researchers explored innovative therapeutic strategies leveraging advanced modified mRNA (mod-RNA) technology. By designing mod-RNA constructs to selectively silence components of the IFN-I signaling axis within the heart, they successfully attenuated the deleterious immune activation without compromising systemic antiviral defenses. Treatment with this mod-RNA therapeutic in murine models resulted in a significant decrease in cardiac troponin levels and preservation of LVEF, highlighting its potential as a cardiac-protective intervention during severe influenza infection.
The implications of these findings extend beyond influenza alone, offering a blueprint for addressing viral myocarditis and other infection-triggered cardiovascular disorders mediated by immune dysregulation. Current clinical management of influenza predominantly focuses on respiratory symptoms, with limited options to prevent secondary cardiac complications. The Mount Sinai study pioneers a shift toward precision immunomodulation, targeting specific immune pathways implicated in tissue damage, thereby enhancing patient outcomes in at-risk populations.
Ongoing collaborative efforts are directed toward optimizing the delivery methods of the mod-RNA therapeutic. The initial proof-of-concept utilized direct cardiac injections, a technique not readily translatable to clinical practice. Researchers are investigating systemic delivery platforms that can efficiently target myocardial cells, aiming for minimally invasive and scalable treatment protocols. Concurrently, fundamental studies into the biology of pDC3 cells aim to delineate their susceptibility mechanisms to influenza and explore methods to harness their antiviral potential while curbing their pathological effects.
This research underscores the critical intersection of infectious disease and cardiovascular health, emphasizing the intricate balance between protective immunity and immunopathology. As influenza viruses persistently evolve and continue to pose pandemic threats, understanding host-pathogen interactions at a cellular and molecular level is indispensable. The work from Mount Sinai exemplifies how translational research can uncover hidden disease mechanisms and accelerate the development of next-generation therapeutics tailored to complex viral syndromes.
Cardiovascular complications of infectious diseases remain a significant yet underappreciated challenge in healthcare. Mount Sinai’s findings bring to light the need for integrated clinical approaches that monitor cardiac health during viral infections and apply targeted immunotherapies where appropriate. With cardiovascular disease already a leading cause of morbidity worldwide, strategies that prevent infection-induced exacerbations could substantially reduce healthcare burdens.
Mount Sinai Health System, renowned for its leadership in cardiology and cardiac surgery, continues to leverage its clinical and scientific expertise to confront emerging health crises. The institution’s commitment to translational medicine and innovative technologies, such as mod-RNA therapies, sets a foundation for transformative treatments that address multi-organ impacts of viral infections. Such advances hold promise not only for influenza but also other viral diseases with cardiovascular manifestations, including COVID-19 and emerging zoonoses.
Looking forward, deeper interrogation of IFN-I signaling networks and myeloid cell biology during viral infections may reveal additional therapeutic targets. The precise modulation of immune responses to prevent collateral tissue damage represents a frontier in infection management. The Mount Sinai study serves as a clarion call to the scientific community to prioritize immune-based strategies that reconcile antiviral efficacy with organ protection, ultimately enhancing patient survival in severe viral illnesses.
Subject of Research: People
Article Title: Influenza hijacks circulating myeloid cells to inflict IFN-I-fueled damage in the heart
News Publication Date: 9-Feb-2026
Image Credits: Mount Sinai Health System
Keywords: Influenza viruses, Influenza, Cardiology, Cardiovascular disorders, Cell pathology, Medical treatments
Tags: flu seasons and heart attack correlationhuman autopsy studies on influenza patientsimmune response to influenza virusinfluenza A virus and myocardium injuryinfluenza infection and heart diseasemolecular connection between flu and cardiovascular complicationsmouse models in influenza researchpreexisting cardiovascular conditions and flu riskrole of pro-dendritic cells in influenza infectionsystemic impacts of respiratory pathogens on heart healthtargeted therapeutics for virus-induced heart damagetype I interferon and cardiac tissue damage
