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Proc Natl Acad Sci U S A. 2019 May 28;116(22):10905-10910. doi: 10.1073/pnas.1902840116. Epub 2019 May 13.

Low ambient humidity impairs barrier function and innate resistance against influenza infection.

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Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520.
Department of Pathology, Yale University School of Medicine, New Haven, CT 06520.
Department of Pathology and Laboratory Medicine, Veterans Affairs Connecticut Healthcare System, West Haven, CT 06516.
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520;
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511.
Howard Hughes Medical Institute, Chevy Chase, MD 20815.


In the temperate regions, seasonal influenza virus outbreaks correlate closely with decreases in humidity. While low ambient humidity is known to enhance viral transmission, its impact on host response to influenza virus infection and disease outcome remains unclear. Here, we showed that housing Mx1 congenic mice in low relative humidity makes mice more susceptible to severe disease following respiratory challenge with influenza A virus. We find that inhalation of dry air impairs mucociliary clearance, innate antiviral defense, and tissue repair. Moreover, disease exacerbated by low relative humidity was ameliorated in caspase-1/11-deficient Mx1 mice, independent of viral burden. Single-cell RNA sequencing revealed that induction of IFN-stimulated genes in response to viral infection was diminished in multiple cell types in the lung of mice housed in low humidity condition. These results indicate that exposure to dry air impairs host defense against influenza infection, reduces tissue repair, and inflicts caspase-dependent disease pathology.


disease tolerance; flu season; interferon; mucosal immunity; respiratory tract

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