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

Research output: Contribution to journalArticlepeer-review

224 Citations (Scopus)

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 with multiple zoonotic viruses including influenza A virus (−single-stranded (ss) RNA), Melaka virus (PRV3M, double-stranded RNA) and Middle East respiratory syndrome coronavirus (+ssRNA) was observed. Importantly, this reduction of inflammation had no impact on the overall viral loads. We identified dampened transcriptional priming, a novel splice variant and an altered leucine-rich repeat domain of bat NLRP3 as the cause. Our results elucidate an important mechanism through which bats dampen inflammation with implications for longevity and unique viral reservoir status.

Original languageEnglish
Pages (from-to)789-799
Number of pages11
JournalNature Microbiology
Volume4
Issue number5
DOIs
Publication statusPublished - 1 May 2019
Externally publishedYes

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