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

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.