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

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 (Nlrp3R258W) are strongly resistant to IAV infection. Upon H1N1 IAV infection, the Nlrp3R258W mice exhibited decreased weight loss, increased survival rate and attenuated lung damage compared with WT littermate controls. Mechanistically, the resistance of Nlrp3R258W mice to IAV infection was dependent on IL-1β-mediated neutrophil recruitment. Upon IAV infection, mice carrying the Nlrp3R258W 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 Nlrp3R258W mice was lower than that in control mice. Conversely, neutrophil depletion in Nlrp3R258W 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.

• Authors: Junling Niu, Shuxian Wu, Mingkuan Chen, Ke Xu, Qiuhong Guo, Ailing Lu, Liping Zhao, Bing Sun, Guangxun Meng
• Journal: Cytokine (Cytokine) Vol. 120 Pg. 115-124 (08 2019) ISSN: 1096-0023 [Electronic] England
• PMID: 31055218 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• Inflammasomes
• Interleukin-1beta
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse

Topics

• Animals
• Inflammasomes (metabolism)
• Inflammation (pathology)
• Influenza A virus (immunology)
• Interleukin-1beta (metabolism)
• Lung (pathology, virology)
• Mice
• Mice, Inbred C57BL
• Mutation (genetics)
• NLR Family, Pyrin Domain-Containing 3 Protein (genetics, metabolism)
• Neutrophil Infiltration
• Orthomyxoviridae Infections (immunology, prevention & control, virology)
• Signal Transduction