Treponema pallidum recombinant protein Tp47 activates NOD-like receptor family protein 3 inflammasomes in macrophages via glycolysis.

Glycolysis Macrophage NLRP3 inflammasome Tp47 Treponema pallidum

Journal

International immunopharmacology
ISSN: 1878-1705
Titre abrégé: Int Immunopharmacol
Pays: Netherlands
ID NLM: 100965259

Informations de publication

Date de publication:
27 Nov 2023
Historique:
received: 10 09 2023
revised: 31 10 2023
accepted: 07 11 2023
medline: 29 11 2023
pubmed: 29 11 2023
entrez: 28 11 2023
Statut: aheadofprint

Résumé

Glycolysis is a key pathway in cellular glucose metabolism for energy supply and regulates immune cell activation. Whether glycolysis is involved in the activation of NOD-like receptor family protein 3 (NLRP3) inflammasomes during Treponema pallidum (T. pallidum) infection is unclear. In this study, the effect of T. pallidum membrane protein Tp47 on NLRP3 inflammasome activation in rabbit peritoneal macrophages was analysed and the role of glycolysis in NLRP3 inflammasome activation was explored. The results showed that Tp47 promoted NLRP3, caspase-1, and IL-1β mRNA expression in macrophages, enhanced glycolysis and glycolytic capacity of macrophage, and promoted the production of macrophage glycolytic metabolites citrate, phosphoenolpyruvate, and lactate. The M2 pyruvate kinase (PKM2) inhibitor shikonin down-regulated the Tp47-promoted NLRP3, caspase-1, and IL-1β mRNA expression in macrophages, and suppressed the Tp47-enhanced glycolysis and glycolytic capacity. Similarly, si-PKM2 significantly inhibited Tp47-promoted NLRP3, caspase-1, and IL-1β mRNA expression and the Tp47-enhanced glycolysis and glycolytic capacity in macrophages. In conclusion, Tp47 activated NLRP3 inflammasomes via PKM2-dependent glycolysis and provided a new perspective on the effect of T. pallidum infection on host macrophages, which would contribute to the understanding of the infection mechanism and host immune mechanism of T. pallidum.

Identifiants

DOI: 10.1016/j.intimp.2023.111204 PMID: 38016343
pubmed: 38016343
pii: S1567-5769(23)01531-X
doi: 10.1016/j.intimp.2023.111204
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

111204

Informations de copyright

Copyright © 2023 Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Xin-Qi Zheng (XQ)

Center of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen 361004, China.

Ze Li (Z)

Center of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen 361004, China.

Qing-Qi Meng (QQ)

Center of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen 361004, China.

Wei Li (W)

Center of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen 361004, China.

Qiu-Ling Li (QL)

Center of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen 361004, China.

Lin Xie (L)

Center of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen 361004, China.

Yao Xiao (Y)

Center of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen 361004, China; Department of Hospital Infection Management, School of Medicine, Zhongshan Hospital of Xiamen University, Xiamen University, Xiamen, China. Electronic address: xiaoyao@xmu.edu.cn.

Qiu-Yan Xu (QY)

Center of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen 361004, China. Electronic address: xuqiuyan12@163.com.

Yu-Yan Chen (YY)

Center of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China; Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen 361004, China. Electronic address: chenyuyan@xmu.edu.cn.

Classifications MeSH