Journal article

Dampened NLRP3-mediated inflammation in bats and implications for a special viral reservoir host

Matae Ahn, Danielle E Anderson, Qian Zhang, Chee Wah Tan, Beng Lee Lim, Katarina Luko, Ming Wen, Wan Ni Chia, Shailendra Mani, Loo Chien Wang, Justin Han Jia Ng, Radoslaw M Sobota, Charles-Antoine Dutertre, Florent Ginhoux, Zheng-Li Shi, Aaron T Irving, Lin-Fa Wang

Nature Microbiology | NATURE PUBLISHING GROUP | Published : 2019

Abstract

Bats are special in their ability to host emerging viruses. As the only flying mammal, bats endure high metabolic rates yet exhibit elongated lifespans. It is currently unclear whether these unique features are interlinked. The important inflammasome sensor, NLR family pyrin domain containing 3 (NLRP3), has been linked to both viral-induced and age-related inflammation. Here, we report significantly dampened activation of the NLRP3 inflammasome in bat primary immune cells compared to human or mouse counterparts. Lower induction of apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and secretion of interleukin-1β in response to both 'sterile' stimuli and infection..

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Grants

Awarded by Singapore National Research Foundation


Awarded by New Investigator's Grant from the National Medical Research Council of Singapore


Awarded by National Natural Science Foundation of China


Awarded by NMRC MS-CETSA platform grant


Funding Acknowledgements

This work was funded by the Singapore National Research Foundation (grants NRF2012NRF-CRP001-056 to F.G. and L.-F.W. and NRF2016NRF-NSFC002-013 to L.-F.W.), a New Investigator's Grant (to A.T.I.) from the National Medical Research Council of Singapore (NMRC/BNIG/2040/2015) and the National Natural Science Foundation of China (31621061). R.M.S. is supported by a Young Investigator Grant YIG 2015 (BMRC, A*STAR) and NMRC MS-CETSA platform grant (MOHIAFCAT2/004/2015). The authors thank the following for help with bat sampling: Crameri Research Consulting, J. Meers, H. Field and Duke-NUS team members (for a detailed listing see Supplementary Information). The authors thank A. Bertoletti and A. T. Tan for use of the Amnis ImageStream. The authors give special thanks to E. Latz for providing the immortalized NLRP3-knockout macrophages. The authors also acknowledge the facilities and technical assistance of the Advanced Bioimaging Core and Flow Cytometry Core at SingHealth Duke-NUS Academic Medical Centre, and X. F. Lim and S. Velraj for their valuable assistance in the Duke-NUS ABSL3 Facility.