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  3. The critical role of NLRP3 inflammasome activation in Streptococcus suis-induced blood-brain barrier disruption

The critical role of NLRP3 inflammasome activation in Streptococcus suis-induced blood-brain barrier disruption

  • Vet Microbiol. 2024 Aug:295:110161. doi: 10.1016/j.vetmic.2024.110161.
Xinrui Cao 1,  Kaixiang Jia 1,  Qian Liu 1,  Hang Yin 1,  Xiaoying Yu 1,  Xiaoxiang Hu 1,  Chao Ye 1,  Lianci Peng 2,  Rendong Fang 3
Affiliations

Affiliations

  • 1 Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing 400715, China.
  • 2 Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing 400715, China; National Center of Technology Innovation for Pigs, Chongqing 402460, China. Electronic address: penglianci@swu.edu.cn.
  • 3 Joint International Research Laboratory of Animal Health and Animal Food Safety, College of Veterinary Medicine, Southwest University, Chongqing 400715, China; National Center of Technology Innovation for Pigs, Chongqing 402460, China. Electronic address: rdfang@swu.edu.cn.
PMID: 38945021 DOI: 10.1016/j.vetmic.2024.110161
Abstract

Streptococcus suis (S. suis) type 2 (SS2) is an important zoonotic pathogen causing severe neural infections in pigs and causes serious threat to public health. Inflammasome activation plays an important role in the host against microbial Infection but the role of inflammasome activation in the blood-brain barrier (BBB) integrity during S. suis Infection is rarely studied. This study investigated the mechanism by which S. suis-induced NLRP3 inflammasome activation led to BBB disruption. Our results showed that S. suis Infection activated NLRP3 inflammasome in brain microvascular endothelial cells (BMECs) leading to the secretion of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and chemokines (CCL-2 and CXCL-2) as well as the cleavage of Gasdermin D (GSDMD) which were significantly attenuated by inflammasome inhibitor MCC950. Furthermore, S. suis Infection significantly downregulated expression of tight junctions (TJs) proteins and trans-endothelial electrical resistance (TEER) while NLRP3 inhibition rescued S. suis-induced degradation of TJs proteins and significantly reduced the number of S. suis crossing BBB in transwell Infection model. Moreover, recombinant IL-1β exacerbated the reduction of TJs proteins in BMECs. In murine S. suis-infection model, MCC950 reduced the Bacterial load and the excessive inflammatory response in mice brain. In addition, the integrity of the BBB was protected with increased TJ proteins expression and decreased pathological injury after the inhibition of NLRP3 inflammasome, indicating NLRP3 inflammasome plays a destructive role in meningitis induced by S. suis. Our study expands the understanding on the role of NLRP3 inflammasome in Bacterial meningitis, which provide the valuable information for the development of anti-infective agents targeting NLRP3 to treat Bacterial meningitis.

Keywords

Blood-brain barrier; NLRP3 inflammasome; Streptococcus suis.

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