2. Academic Validation
  3. Activation of the NLRP3-CASP-1 inflammasome is restrained by controlling autophagy during Glaesserella parasuis infection

Activation of the NLRP3-CASP-1 inflammasome is restrained by controlling autophagy during Glaesserella parasuis infection

  • Vet Microbiol. 2024 Aug:295:110160. doi: 10.1016/j.vetmic.2024.110160.
Chaoxiong Yue 1,  Jinquan Li 2,  Siming Zhang 2,  Ruyi Ma 2,  Mingjiao Suo 2,  Yiwen Chen 2,  Hui Jin 3,  Yan Zeng 4,  Yushan Chen 5
Affiliations

Affiliations

  • 1 Brain Science and Advanced Technology Institute, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, China; State Key Laboratory of Virology and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
  • 2 Brain Science and Advanced Technology Institute, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, China.
  • 3 State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
  • 4 Brain Science and Advanced Technology Institute, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, China. Electronic address: zengyan68@wust.edu.cn.
  • 5 Brain Science and Advanced Technology Institute, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, China. Electronic address: yschen@wust.edu.cn.
PMID: 38964034 DOI: 10.1016/j.vetmic.2024.110160
Abstract

Infection with Glaesserella parasuis, the primary pathogen behind Glässer's disease, is often associated with diverse clinical symptoms, including serofibrinous polyserositis, arthritis, and meningitis. Autophagy plays a dual role in Bacterial infections, exerting either antagonistic or synergistic effects depending on the nature of the pathogen. Our previous studies have demonstrated that Autophagy serves as a defense mechanism, combating inflammation and invasion caused by Infection of highly virulent G. parasuis. However, the precise mechanisms remain to be elucidated. Pathogens exhibit distinct interactions with inflammasomes and Autophagy processes. Herein, we explored the effect of Autophagy on inflammasomes during G. parasuis Infection. We found that G. parasuis Infection triggers NLRP3-dependent pro-CASP-1-IL-18/IL-1β processing and maturation pathway, resulting in increased release of IL-1β and IL-18. Inhibition of Autophagy enhances NLRP3 inflammasome activity, whereas stimulation of Autophagy restricts it during G. parasuis Infection. Furthermore, assembled NLRP3 inflammasomes undergo ubiquitination and recruit the autophagic adaptor, p62, facilitating their sequestration into autophagosomes during G. parasuis Infection. These results suggest that the induction of Autophagy mitigates inflammation by eliminating overactive NLRP3 inflammasomes during G. parasuis Infection. Our research uncovers a mechanism whereby G. parasuis Infection initiates inflammatory responses by promoting the assembly of the NLRP3 inflammasomes and activating NLRP3-CASP-1, both of which processes are downregulated by Autophagy. This suggests that pharmacological manipulation of Autophagy could be a promising approach to modulate G. parasuis-induced inflammatory responses.

Keywords

Autophagy; CASP-1; Glaesserella parasuis; Inflammasome; NLRP3.

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