Bat ASC2 suppresses inflammasomes and ameliorates inflammatory diseases
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....
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Published in | Cell Vol. 186; no. 10; pp. 2144 - 2159.e22 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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United States
Elsevier Inc
11.05.2023
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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.
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•ASC2 is universally present and highly expressed in bats•Bat ASC2 is highly potent in dampening inflammasomes via ASC•Bat ASC2 attenuates sterile and virus-induced inflammation in mouse models•Mutation of 4 residues in human ASC2 allows it to gain bat-ASC2-like functionality
Bats harbor many viruses and are long-lived. Bat ASC2, unlike its human counterpart, is a potent negative regulator of inflammasomes, thereby revealing a fundamentally distinct property of reduced inflammation in these animals in response to viruses and danger signals. |
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AbstractList | 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. 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. [Display omitted] •ASC2 is universally present and highly expressed in bats•Bat ASC2 is highly potent in dampening inflammasomes via ASC•Bat ASC2 attenuates sterile and virus-induced inflammation in mouse models•Mutation of 4 residues in human ASC2 allows it to gain bat-ASC2-like functionality Bats harbor many viruses and are long-lived. Bat ASC2, unlike its human counterpart, is a potent negative regulator of inflammasomes, thereby revealing a fundamentally distinct property of reduced inflammation in these animals in response to viruses and danger signals. |
Author | Ng, Wei Lun Sobota, Radoslaw M. Chan, Wharton O.Y. Ahn, Matae Cheong, Wan Shoo Chia, Wan Ni Kong, Pui San Zhu, Feng Su, Qi Rozario, Pritisha Wang, Lin-Fa Guo, Fusheng Li, Xin Nguyen, Lan Huong Fu, Nai Yang Tan, Chee Wah Kang, Adrian Eng Zheng Foo, Randy Hey, Ying Ying Lim, Yan Ting Chen, Vivian Chih-Wei Irving, Aaron T. Sia, Wan Rong |
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Keywords | bats COVID-19 SARS-CoV-2 disease resistance inflammation inflammasome immune complex inflammatory diseases longevity viral reservoir |
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Snippet | 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... |
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SubjectTerms | Animals Apoptosis Regulatory Proteins - metabolism bats Chiroptera - immunology COVID-19 disease resistance Humans immune complex inflammasome Inflammasomes - immunology inflammation inflammatory diseases longevity Mice Ribonucleoproteins - metabolism SARS-CoV-2 viral reservoir Virus Diseases - immunology Virus Physiological Phenomena |
Title | Bat ASC2 suppresses inflammasomes and ameliorates inflammatory diseases |
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