Jing Xie , Nan Xie , Chang Liu , Zhemin Huang , Min Du , Hao Hu , Kang Zheng , Jiaofeng Peng , Ranhui Li
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引用次数: 0
Abstract
The pathogenesis of Ureaplasma urealyticum infection is linked to the host inflammatory response; however, the specific molecular mechanisms underlying this phenomenon have not been fully elucidated. GrpE is a chaperonin that accelerates ADP release and ATP binding to DnaK, thereby enhancing the chaperone function of the HSP70 system under stress. However, alternative activities such as pro-inflammatory responses remain poorly understood. In this study, we report that the U. urealyticum GrpE exerts as a cytokine-inducing virulence factor toward macrophages. Using gene-knockout mice and specific inhibitors, we found that GrpE-induced pro-inflammatory cytokine expression was mediated by the TLR2/STAT3 pathway. We also found that glycolysis was essential for this pro-inflammatory response. Mechanistically, GrpE treatment stimulated STAT3-dependent accumulation of citric acid and acetyl-CoA, promoting histone acetylation and potent pro-inflammatory responses. Our results indicate that glycolysis plays a role in the inflammatory response induced by GrpE through the TLR2/STAT3 pathway and contributes to the glycolysis-mediated inflammatory response, offering a fresh understanding of the development of U. urealyticum infection.
期刊介绍:
Immunobiology is a peer-reviewed journal that publishes highly innovative research approaches for a wide range of immunological subjects, including
• Innate Immunity,
• Adaptive Immunity,
• Complement Biology,
• Macrophage and Dendritic Cell Biology,
• Parasite Immunology,
• Tumour Immunology,
• Clinical Immunology,
• Immunogenetics,
• Immunotherapy and
• Immunopathology of infectious, allergic and autoimmune disease.