Vibrio vulnificus hemolysin drives NLRP3 inflammasome activation in platelets via TRPC6-mediated calcium signaling
5 affiliations
- 1State Key Laboratory of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
- 2Department of Medical Equipment, Qingyang Hospital of Traditional Chinese Medicine, Qingyang, China
- 3Department of Disease Control and Prevention, The No.96609 Hospital of Chinese People's Liberation Army, Yinchuan, China
- 4State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences (AMMS), Beijing, China
- 5Department of Disease Control, The Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University, Wuxi Center for Disease Control and Prevention, Wuxi, 214023 China
Abstract
Vibrio vulnificus, an opportunistic pathogenic species, predominantly induces sepsis in patients with liver disease rather than in healthy individuals, although its opportunistic pathogenic mechanisms are unclear. The role and mechanisms behind the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation induced by V. vulnificus infection in normal mice or healthy humans, serving as a core sensor and signal amplifier of the innate immune system in platelets, have not been elucidated. Here we discovered that V. vulnificus hemolysin (VVH), a member of Cholesterol-dependent cytolysins, rather than multifunctional auto processing Repeats-in-Toxins (MARTX), is the specific effector of V. vulnificus, activating the NLRP3 inflammasome, platelet pyroptosis, necroptosis, and increasing IL-1β expression. Mechanistically, rather than ROS production, VVH-induced the intracellular Ca2+ increasing is essential for triggering NLRP3 inflammasome activation in platelet, which are mediated by the classical transient receptor potential channel 6 (TRPC6)-triggering Ca2+ influx and calcium-induced calcium release. The pharmacological inhibito of transient receptor potential channel (SKF-96365) partially alleviated inflammation and increased mortality in murine infection models. Furthermore, activating VVH toxin-NLRP3 inflammasome axis in platelets contributes to bacterial clearance in host. This study provides a novel perspective on opportunistic pathogen-host interactions, in which Cholesterol-dependent cytolysin acts as danger signals sensed by the host to activate NLRP3 inflammasome to trigger host immune defense.
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BibTeX
@article{li2026vibrio,
title = {{Vibrio vulnificus hemolysin drives NLRP3 inflammasome activation in platelets via TRPC6-mediated calcium signaling}},
author = {Shi-Qing Li and Yan Wang and Zi-Han Feng and Jian-Hao Xu and Bin Ji and Jing-Lin Wang and Yuan Yuan},
journal = {The Journal of Biological Chemistry},
year = {2026},
month = sep,
doi = {10.1016/j.jbc.2026.113587},
url = {https://doi.org/10.1016/j.jbc.2026.113587},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Vibrio vulnificus hemolysin drives NLRP3 inflammasome activation in platelets via TRPC6-mediated calcium signaling
AU - Shi-Qing Li
AU - Yan Wang
AU - Zi-Han Feng
AU - Jian-Hao Xu
AU - Bin Ji
AU - Jing-Lin Wang
AU - Yuan Yuan
PY - 2026
DA - 2026/09/23
JO - The Journal of Biological Chemistry
DO - 10.1016/j.jbc.2026.113587
UR - https://doi.org/10.1016/j.jbc.2026.113587
AB - Vibrio vulnificus, an opportunistic pathogenic species, predominantly induces sepsis in patients with liver disease rather than in healthy individuals, although its opportunistic pathogenic mechanisms are unclear. The role and mechanisms behind the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation induced by V. vulnificus infection in normal mice or healthy humans, serving as a core sensor and signal amplifier of the innate immune system in platelets, have not been elucidated. Here we discovered that V. vulnificus hemolysin (VVH), a member of Cholesterol-dependent cytolysins, rather than multifunctional auto processing Repeats-in-Toxins (MARTX), is the specific effector of V. vulnificus, activating the NLRP3 inflammasome, platelet pyroptosis, necroptosis, and increasing IL-1β expression. Mechanistically, rather than ROS production, VVH-induced the intracellular Ca2+ increasing is essential for triggering NLRP3 inflammasome activation in platelet, which are mediated by the classical transient receptor potential channel 6 (TRPC6)-triggering Ca2+ influx and calcium-induced calcium release. The pharmacological inhibito of transient receptor potential channel (SKF-96365) partially alleviated inflammation and increased mortality in murine infection models. Furthermore, activating VVH toxin-NLRP3 inflammasome axis in platelets contributes to bacterial clearance in host. This study provides a novel perspective on opportunistic pathogen-host interactions, in which Cholesterol-dependent cytolysin acts as danger signals sensed by the host to activate NLRP3 inflammasome to trigger host immune defense.
SN - 0021-9258
SN - 1083-351X
ER -