2. Academic Validation
  3. Microbiota-derived acetate enhances host antiviral response via NLRP3

Microbiota-derived acetate enhances host antiviral response via NLRP3

  • Nat Commun. 2023 Feb 6;14(1):642. doi: 10.1038/s41467-023-36323-4.
Junling Niu 1 2,  Mengmeng Cui 1,  Xin Yang 2,  Juan Li 1 3,  Yuhui Yao 1 4,  Qiuhong Guo 1,  Ailing Lu 1,  Xiaopeng Qi 5,  Dongming Zhou 1,  Chenhong Zhang 6,  Liping Zhao 7 8,  Guangxun Meng 9 10 11
Affiliations

Affiliations

  • 1 The Center for Microbes, Development and Health, CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, University of Chinese Academy of Sciences, 200031, Shanghai, China.
  • 2 State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 200240, Shanghai, China.
  • 3 Nanjing Advanced Academy of Life and Health, 211135, Nanjing, China.
  • 4 Pasteurien College, Soochow University, 215006, Suzhou, Jiangsu, China.
  • 5 CAS Key Laboratory of Animal Models and Human Disease Mechanisms/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, 650201, Kunming, Yunnan, China.
  • 6 State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 200240, Shanghai, China. [email protected].
  • 7 State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 200240, Shanghai, China. [email protected].
  • 8 Department of Biochemistry and Microbiology and New Jersey Institute for Food, Nutrition, and Health, School of Environmental and Biological Sciences, Rutgers University, NJ, 08901, USA. [email protected].
  • 9 The Center for Microbes, Development and Health, CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, University of Chinese Academy of Sciences, 200031, Shanghai, China. [email protected].
  • 10 Nanjing Advanced Academy of Life and Health, 211135, Nanjing, China. [email protected].
  • 11 Pasteurien College, Soochow University, 215006, Suzhou, Jiangsu, China. [email protected].
PMID: 36746963 DOI: 10.1038/s41467-023-36323-4
Abstract

Pathogenic viral infections represent a major challenge to human health. Host immune responses to respiratory viruses are closely associated with microbiome and metabolism via the gut-lung axis. It has been known that host defense against influenza A virus (IAV) involves activation of the NLRP3 inflammasome, however, mechanisms behind the protective function of NLRP3 are not fully known. Here we show that an isolated Bacterial strain, Bifidobacterium pseudolongum NjM1, enriched in the gut microbiota of Nlrp3-/- mice, protects wild-type but not Nlrp3 deficient mice against IAV Infection. This effect depends on the enhanced production of type I interferon (IFN-I) mediated by NjM1-derived acetate. Application of exogenous acetate reproduces the protective effect of NjM1. Mechanistically, NLRP3 bridges GPR43 and MAVS, and promotes the oligomerization and signalling of MAVS; while acetate enhances MAVS aggregation upon GPR43 engagement, leading to elevated IFN-I production. Thus, our data support a model of NLRP3 mediating enhanced induction of IFN-I via acetate-producing bacterium and suggest that the acetate-GPR43-NLRP3-MAVS-IFN-I signalling axis is a potential therapeutic target against respiratory viral infections.

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