A research project on stress and respiratory infectious diseases has been awarded a Takeda Science Foundation Grant.

Understanding Respiratory Barrier Dysfunction and Host Responses to Respiratory Viral Infection Under Chronic Stress

Funding Program: Takeda Science Foundation – Medical Research Grant (Infectious Diseases), 2023
Principal Investigator: Yukiko Akahori

Chronic psychological and physical stress is known to increase susceptibility to respiratory infections such as the common cold; however, its effects on the respiratory barrier and antiviral host defense remain poorly understood. In this project, we established two murine models of chronic stress—social isolation (SI) and unpredictable chronic mild stress (UCMS)—to investigate stress-induced alterations in the respiratory barrier and host responses to influenza virus infection.

Behavioral analyses demonstrated increased depression-like behavior in SI mice, whereas UCMS mice exhibited hyperactivity-like phenotypes. Analysis of the nasal microbiota revealed a marked shift in microbial composition in SI mice, suggesting that chronic social isolation alters the nasal microenvironment. Following influenza virus infection, SI mice developed more severe pulmonary edema and exhibited reduced survival, whereas UCMS mice showed increased resistance to infection.

These findings suggest that different forms of chronic stress differentially modulate the respiratory barrier, mucosal microbiota, and host immune responses, thereby influencing the severity of influenza virus infection. Ongoing studies will further investigate lung pathology and microbiome dynamics to elucidate the molecular mechanisms linking chronic stress to respiratory infectious diseases, providing new insights into the interactions between psychological stress, mucosal immunity, and viral pathogenesis.