Seasonal PM 2.5 exposures induce differential responses to influenza A virus infection in primary human airway epithelial cells

Background Air pollution, specifically fine particulate matter (PM _2.5 ), in China is responsible for millions of excess deaths each decade. Examinations of Chinese municipalities have revealed correlations between ambient PM _2.5 levels and the prevalence and severity of respiratory viral infections. Seasonal sources of ambient PM _2.5 vary, with coal combustion for indoor heating significantly contributing during colder months. Due to this seasonality, we sought to investigate whether exposure to seasonal PM _2.5 collected in Xinxiang, China would differentially alter the response to subsequent influenza A/California/04/2009 (H1N1) viral infection in a primary human nasal epithelial cell (HNEC) culture model. After the PM _2.5 samples were chemically analyzed, HNECs collected from males (N = 4) and females (N = 3) grown at air-liquid interface were exposed to 22 µg/cm ² of seasonal PM _2.5 followed by inoculation with influenza A H1N1 at MOI = 0.001. At 2 and 24 h post infection (p.i.) we assessed transcriptional changes and basolateral release of immune and antiviral mediators. Results Summer and fall PM _2.5 samples contained a greater organic carbon mass fraction compared to winter and spring. Winter contained the largest mass fraction of anionic components and spring the largest inorganic element mass fraction. In response to infection alone without PM _2.5 exposure, the transcriptional response to infection at 24 h p.i. differed between the sexes with males having more robust interferon pathway activation. Exposure to the seasonal PM _2.5 samples without infection induced a moderate transcriptional response at 2 h, with the winter PM _2.5 inducing the greatest response. The seasonal PM _2.5 exposures followed by viral infection resulted in a more robust transcriptional response at 2 h p.i. with the winter, spring, and fall PM _2.5 samples (but not the summer PM _2.5 ) upregulating many inflammatory pathways. At 24 h p.i., only the spring PM _2.5 sample increased inflammatory and antiviral mediator proteins in the basolateral medium, while winter PM _2.5 increased these inflammatory markers in the mock infected cultures. Conclusions Chemical differences in seasonal PM _2.5 from the winter, spring, and fall, coinciding with influenza season, likely contribute to the adjuvant pro-inflammatory effects of exposure on antiviral host response. Heightened inflammation early in infection could contribute to worsened pathogenesis.