Abstract
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.
Highlights
In the temperate regions, seasonal influenza virus outbreaks correlate closely with decreases in humidity
We show that mice kept at low relative humidity (10–20% RH) experience more severe symptoms than those kept at higher relative humidity (50% RH)
Mx1 mice at 50% RH were infected with varying doses of highly virulent Influenza A viruses (IAVs) PR8 strain to determine the LD50 (SI Appendix, Fig. S1)
Summary
Low ambient humidity impairs barrier function and innate resistance against influenza infection. While low ambient humidity is known to enhance viral transmission, its impact on host response to influenza virus infection and disease outcome remains unclear. Single-cell RNA sequencing revealed that induction of IFNstimulated 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. Experimental studies in guinea pigs demonstrate that low temperature and low humidity enable aerosol transmission of influenza virus, providing one explanation for the seasonality of viral transmission [10] While these studies clearly show that environmental conditions affect transmission of influenza virus, the impact of ambient humidity on host response to influenza virus infection and disease outcome remains unclear. Our data suggest that controlling the relative humidity is important to prevent influenza infection and disease outcomes in the dry winter season
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