Format

Send to

Choose Destination
Nat Microbiol. 2019 May;4(5):789-799. doi: 10.1038/s41564-019-0371-3. Epub 2019 Feb 25.

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

Author information

1
Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.
2
CAS Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
3
University of Chinese Academy of Sciences, Beijing, China.
4
Functional Proteomics Laboratory, Institute of Molecular and Cellular Biology (A*STAR), Singapore, Singapore.
5
Institute of Medical Biology (IMB), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
6
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
7
Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore. aaron.irving@duke-nus.edu.sg.
8
Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore. linfa.wang@duke-nus.edu.sg.

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.

Comment in

PMID:
30804542
DOI:
10.1038/s41564-019-0371-3

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center