Hyperactivation of the NLRP3 inflammasome protects mice against influenza A virus infection via IL-1β mediated neutrophil recruitment. (August 2019)

• Record Type: Journal Article
• Authors: Niu, Junling; Wu, Shuxian; Chen, Mingkuan; Xu, Ke; Guo, Qiuhong; Lu, Ailing; Zhao, Liping; Sun, Bing; Meng, Guangxun
• Is Part Of: Cytokine. Volume 120(2019)
• Page Start: 115
• Page End: 124
• Publication Date: 2019-08
• Subjects: NLRP3 inflammasome -- Influenza -- Neutrophil; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2019.04.019
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: Nlrp3 R258W mutation protects against influenza-induced pathology. The attenuated pathology correlates with enhanced influenza virus clearance. The enhanced virus clearance is attributed to neutrophil recruitment. The neutrophil recruitment is mediated by IL-1β signaling. Increased IL-1β secretion originates from the Nlrp3 R258W mutation. Abstract: Host innate immune system is critical for combating invading microbes including Influenza A virus (IAV). As an important arm of the innate immunity, the NLRP3 inflammasome has been found essential for protecting host against IAV challenge, while the mechanism remained elusive. Here we found that mice carrying a gain-of-function mutation in the Nlrp3 gene ( Nlrp3 R258W ) are strongly resistant to IAV infection. Upon H1N1 IAV infection, the Nlrp3 R258W mice exhibited decreased weight loss, increased survival rate and attenuated lung damage compared with WT littermate controls. Mechanistically, the resistance of Nlrp3 R258W mice to IAV infection was dependent on IL-1β-mediated neutrophil recruitment. Upon IAV infection, mice carrying the Nlrp3 R258W mutation produced more IL-1β than WT mice in the lung, which enhanced neutrophil recruitment locally. The recruited neutrophils facilitated IAV clearance, so that the viral load in Nlrp3 R258W mice was lower than that in control mice. Conversely, neutrophil depletion in Nlrp3 R258W mice compromised IAV clearance. Taken together, our results demonstrate a previously undescribed mechanism by which hyperactivation of the NLRP3 Inflammasome protects mice from IAV infection through IL-1β mediated neutrophil recruitment, thus suggest that positively fine tuning the physiological function of NLRP3 inflammasome can be beneficial for a mammalian host against IAV challenge.