The effect of air pollution on the antiviral immune response in pulmonary fibrosis

<bold>Background</bold> Exposure to fine particles (PM_2.5) has recently been associated with an increased risk of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). To date, air pollution and viral infection are distinct but potentially linked triggers of AE-IPF, although the underlying pathogenic mechanisms remain unclear. <bold>Hypothesis</bold> Components of PM_2.5 impair the antiviral immune response in the lungs, increasing the susceptibility to viral respiratory infections in lung fibrosis. <bold>Methods</bold> Human alveolar type-II epithelial (ATII) cells were cultured for 48h, prior to 24h treatment with up to 100 uM vanadium pentoxide (V₂O₅), a metal component found to be at higher concentrations in PM_2.5 collected at the Port of Southampton. ATII cells were also co-exposed with the viral mimetic poly(I:C) and/or recombinant human TGF-β1 for 24h. Following RNA extraction, interferon-stimulated genes (ISGs) expression was assessed by qRT-PCR. <bold>Results</bold> A significant effect of V₂O₅, mostly at the highest concentration of 100uM, was observed including downregulation of interferon-stimulated gene expression induced by the viral mimetic poly(I:C) in ATII cells. This inhibitory effect of vanadium pentoxide upon interferon-stimulated genes is potentially enhanced in ATII cells co-exposed to vanadium and TGFβ, suggesting an additive effect. <bold>Conclusions</bold> The fibrosis-specific microenvironment may be more vulnerable to the effect of air pollution exposure through the suppression of innate immunity, so increasing the potential risk of acute exacerbation in pulmonary fibrosis.