PM2.5 compromises antiviral immunity in influenza infection by inhibiting activation of NLRP3 inflammasome and expression of interferon-β

PM2.5, a major component of air pollutants, has caused severe health problems. It has been reported that PM2.5 index is closely associated with severity of influenza A virus (IAV) infection. However, the underlying mechanisms have not been addressed. NLRP3 inflammasome and type I interferon signaling regulate host defense against influenza infection. The present study investigated the potential effects of air pollutants on host defense against influenza infection in vitro and in vivo. In this study, different concentrations of PM2.5 were pre-exposed to macrophages and mice before IAV infection to assess the negative effects of air pollutants in virus infection. We found that exposure to PM2.5 deteriorated influenza virus infection via compromising innate immune responses manifested by a decrease IL-1 beta and IFN-beta production in vitro. Meanwhile, mice exposed with PM2.5 were susceptible to PR8 virus infection due to down-regulation of IL-1 beta and IFN-beta. Mechanistically, PM 2.5 exposure suppressed the NLRP3 inflammasome activation and the AHR-TIPARP signaling pathway, by which compromised the anti-influenza immunity. Thus, our study revealed that PM2.5 could alter macrophage inflammatory responses by suppressing LPS-induced activation of NLRP3 inflammasome and expression of IFN-beta during influenza infection. These findings provided us new insights in understanding that PM2.5 combining with influenza infection could enhance the severity of pneumonia.