2. Academic Validation
  3. Bat ASC2 suppresses inflammasomes and ameliorates inflammatory diseases

Bat ASC2 suppresses inflammasomes and ameliorates inflammatory diseases

  • Cell. 2023 May 11;186(10):2144-2159.e22. doi: 10.1016/j.cell.2023.03.036.
Matae Ahn 1,  Vivian Chih-Wei Chen 2,  Pritisha Rozario 2,  Wei Lun Ng 2,  Pui San Kong 2,  Wan Rong Sia 2,  Adrian Eng Zheng Kang 2,  Qi Su 2,  Lan Huong Nguyen 2,  Feng Zhu 2,  Wharton O Y Chan 2,  Chee Wah Tan 2,  Wan Shoo Cheong 2,  Ying Ying Hey 2,  Randy Foo 2,  Fusheng Guo 3,  Yan Ting Lim 4,  Xin Li 4,  Wan Ni Chia 2,  Radoslaw M Sobota 4,  Nai Yang Fu 3,  Aaron T Irving 5,  Lin-Fa Wang 6
Affiliations

Affiliations

  • 1 Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857, Singapore; SingHealth Duke-NUS Medicine Academic Clinical Program, Singapore 168753, Singapore; SingHealth PGY1 Residency Program, Singapore 169608, Singapore; Department of Internal Medicine, Singapore General Hospital, Singapore 169608, Singapore. Electronic address: ahn.matae11@u.duke.nus.edu.
  • 2 Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857, Singapore.
  • 3 Programme in Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore.
  • 4 Functional Proteomics Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore; SingMass - National Mass Spectrometry Laboratory, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A(∗)STAR), Singapore 138673, Singapore.
  • 5 Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857, Singapore; Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Haining 314400, China; Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
  • 6 Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857, Singapore; SingHealth Duke-NUS Global Health Institute, Singapore 169857, Singapore. Electronic address: linfa.wang@duke-nus.edu.sg.
PMID: 37172565 DOI: 10.1016/j.cell.2023.03.036
Abstract

Bats are special in their ability to live long and host many emerging viruses. Our previous studies showed that bats have altered inflammasomes, which are central players in aging and Infection. However, the role of inflammasome signaling in combating inflammatory diseases remains poorly understood. Here, we report bat ASC2 as a potent negative regulator of inflammasomes. Bat ASC2 is highly expressed at both the mRNA and protein levels and is highly potent in inhibiting human and mouse inflammasomes. Transgenic expression of bat ASC2 in mice reduced the severity of peritonitis induced by gout crystals and ASC particles. Bat ASC2 also dampened inflammation induced by multiple viruses and reduced mortality of influenza A virus Infection. Importantly, it also suppressed SARS-CoV-2-immune-complex-induced inflammasome activation. Four key residues were identified for the gain of function of bat ASC2. Our results demonstrate that bat ASC2 is an important negative regulator of inflammasomes with therapeutic potential in inflammatory diseases.

Keywords

COVID-19; SARS-CoV-2; bats; disease resistance; immune complex; inflammasome; inflammation; inflammatory diseases; longevity; viral reservoir.

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