Late Breaking Abstract - The pro-inflammatory activity and role of NLRP3 inflammasome in severe influenza A virus pneumonia

Background: Influenza A virus (IAV) causes seasonal flu, or even great pandemics in the world. The NLRP3 inflammasome in macrophages has been found essential for responding against IAV infection. Severe viral pneumonia usually occurs at later stage, which is about one week, of infection. However, the activity and role of NLRP3 inflammasome at the later stage of IAV infection remain under debate. Methods: IAV H1N1 FM1 strain, murine macrophages and mice were applied.Groups were set as blank group, early (6h in vitro and 24h in mice) stage group, and later (1w) stage group. Then the expression of NLRP3, caspase-1, cleaved caspase-1, IL-1β were investigated by means of RT-qPCR, immunofluorescence, western blot, ELISA both in vitro and in vivo. Pathology in lung was observed, and correlation between severity of pneumonia and activity of NLRP3 inflammasome was performed. Results: The results in vitro indicated that activity of NLRP3 inflammasome was obviously enhanced at later stage of IAV infection. The activity of NLRP3 in mice increased at later stage compared with that at early stage of IAV infection, which was consistent with the findings in vitro. Severe viral pneumonia was noted at later stage of IAV infection, and the severity of pneumonia correlated with the concentration of IL-1β, which represented activity of NLRP3 inflammasome, in serum. Conclusions: NLRP3 inflammasome plays a pro-inflammatory effect in IAV infection. And enhanced expression of NLRP3 inflammasome may participate in the mechanism of severe viral pneumonia at later stage of IAV infection.