Ureaplasma urealyticum GrpE protein elicits glycolysis-mediated inflammatory responses through TLR2 in macrophages

  • Immunobiology. 2025 May;230(3):152902. doi: 10.1016/j.imbio.2025.152902.
Jing Xie  1 ,  Nan Xie  2 ,  Chang Liu  2 ,  Zhemin Huang  1 ,  Min Du  1 ,  Hao Hu  1 ,  Kang Zheng  3 ,  Jiaofeng Peng  4 ,  Ranhui Li  5
Affiliations
  • 1. Department of Obstetrics, Affiliated Hengyang Hospital of Hunan Normal University & Hengyang Central Hospital, Hengyang, 421001, Hunan, China.
  • 2. Institute of Pathogenic Biology, Hengyang Medical College, University of South China, Hengyang, China.
  • 3. Institute of Pathogenic Biology, Hengyang Medical College, University of South China, Hengyang, China; Department of Clinical Laboratory, Affiliated Hengyang Hospital of Hunan Normal University and Hengyang Central Hospital, Hengyang 421001, Hunan, China.
  • 4. Department of Clinical Laboratory, Affiliated Hengyang Hospital of Hunan Normal University and Hengyang Central Hospital, Hengyang 421001, Hunan, China. Electronic address: [email protected].
  • 5. Institute of Pathogenic Biology, Hengyang Medical College, University of South China, Hengyang, China. Electronic address: [email protected].
PMID: 40273504 DOI: 10.1016/j.imbio.2025.152902
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.

Keywords
Glycolysis; GrpE; Inflammatory response; TLR2; Ureaplasma urealyticum.
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