Potential mechanisms mediating PM2.5-induced alterations of H3N2 influenza virus infection and cytokine production in human bronchial epithelial cells

Exposure to particulate matter (PM) has been associated with increased hospital admissions for influenza. Airway epithelial cells are a primary target for inhaled environmental insults including fine PM (PM2.5) and influenza viruses. The potentiation of PM2.5 exposure on the effects of influenza virus on airway epithelial cells has not been adequately elucidated. In this study, the effects of PM2.5 exposure on influenza virus (H3N2) infection and downstream modulation of inflammation and antiviral immune response were investigated using a human bronchial epithelial cell line, BEAS-2B. The results showed that PM2.5 exposure alone increased the production of pro-inflammatory cytokines including interleukin-6 (IL-6) and IL-8 but decreased the production of the antiviral cytokine interferon-beta (IFN-beta) in BEAS-2B cells while H3N2 exposure alone increased the production of IL-6, IL-8, and IFN-beta. Importantly, prior exposure to PM2.5 enhanced subsequent H3N2 infectivity, expression of viral hemagglutinin protein, as well as upregulation of IL-6 and IL-8, but reduced H3N2-induced IFN-beta production. Pre-treatment with a pharmacological inhibitor of nuclear factor-kappa B (NF-kappa B) suppressed pro-inflammatory cytokine production induced by PM2.5, H3N2, as well as PM2.5-primed H3N2 infection. Moreover, antibody-mediated neutralization of Toll-like receptor 4 (TLR4) blocked cytokine production triggered by PM2.5 or PM2.5-primed H3N2 infection, but not H3N2 alone. Taken together, exposure to PM2.5 alters H3N2-induced cytokine production and markers of replication in BEAS-2B cells, which in turn are regulated by NF-kappa B and TLR4.

Automated summary

This study investigated the effects of PM2.5 exposure on influenza virus (H3N2) infection and the subsequent modulation of inflammation and antiviral immune response in human bronchial epithelial cells. The results showed that PM2.5 exposure alone increased pro-inflammatory cytokines but decreased the production of antiviral cytokine IFN-beta. Importantly, prior exposure to PM2.5 enhanced subsequent H3N2 infectivity, expression of viral protein, and upregulation of pro-inflammatory cytokines. Additionally, inhibition of NF-kappa B suppressed cytokine production induced by PM2.5 and H3N2.