Institute of Pathogenic Biology, Basic Medical School, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, Hengyang, Hunan, China.
Microbiol Spectr. 2023 Jun 15;11(3):e0450322. doi: 10.1128/spectrum.04503-22. Epub 2023 Apr 19.
Mycoplasma genitalium is a prokaryotic microorganism that causes urogenital tract infections. M. genitalium protein of adhesion (MgPa) was essential for M. genitalium attachment and subsequent invasion into host cells. Our prior research confirmed that Cyclophilin A (CypA) was the binding receptor for MgPa and MgPa-CypA interaction can lead to the production of inflammatory cytokines. In this study, we revealed that the recombinant MgPa (rMgPa) could inhibit the CaN-NFAT signaling pathway to reduce the level of IFN-γ, IL-2, CD25, and CD69 in Jurkat cells by binding to the CypA receptor. Moreover, rMgPa inhibited the expressions of IFN-γ, IL-2, CD25, and CD69 in primary mouse T cells. Likewise, the expressions of these T cells activation-related molecules in CypA-siRNA-transfected cells and CypA mouse primary T cell was strengthened by rMgPa. These findings showed that rMgPa suppressed T cell activation by downregulating the CypA-CaN-NFAT pathway, and as a result, acted as an immunosuppressive agent. Mycoplasma genitalium is a sexually transmitted bacterium that can co-infect with other infections and causes nongonococcal urethritis in males, cervicitis, pelvic inflammatory disease, premature birth, and ectopic pregnancy in women. The adhesion protein of M. genitalium (MgPa) is the primary virulence factor in the complicated pathogenicity of M. genitalium. This research proved that MgPa could interact with host cell Cyclophilin A (CypA) and prevent T cell activation by inhibiting Calcineurin (CaN) phosphorylation and NFAT nuclear translocation, which clarified the immunosuppression mechanism of M. genitalium to host T cells. Therefore, this study can provide a new idea that CypA can be used for a therapeutic or prophylactic target for M. genitalium infection.
生殖支原体是一种引起泌尿生殖道感染的原核微生物。生殖支原体黏附蛋白（MgPa）是生殖支原体附着和随后侵入宿主细胞所必需的。我们之前的研究证实，亲环素 A（CypA）是 MgPa 的结合受体，MgPa-CypA 相互作用可导致炎症细胞因子的产生。在这项研究中，我们揭示了重组 MgPa（rMgPa）通过与 CypA 受体结合，可抑制钙调神经磷酸酶-NFAT 信号通路，从而降低 Jurkat 细胞中 IFN-γ、IL-2、CD25 和 CD69 的水平。此外，rMgPa 抑制了原代小鼠 T 细胞中 IFN-γ、IL-2、CD25 和 CD69 的表达。同样，rMgPa 可增强 CypA-siRNA 转染细胞和 CypA 小鼠原代 T 细胞中这些 T 细胞激活相关分子的表达。这些发现表明，rMgPa 通过下调 CypA-CaN-NFAT 通路抑制 T 细胞激活，从而发挥免疫抑制作用。生殖支原体是一种性传播细菌，可与其他感染合并感染，导致男性非淋菌性尿道炎、宫颈炎、盆腔炎、早产和女性宫外孕。生殖支原体的黏附蛋白（MgPa）是生殖支原体复杂发病机制中的主要毒力因子。本研究证明，MgPa 可与宿主细胞亲环素 A（CypA）相互作用，并通过抑制钙调神经磷酸酶（CaN）磷酸化和 NFAT 核易位来阻止 T 细胞激活，阐明了生殖支原体对宿主 T 细胞的免疫抑制机制。因此，本研究为 CypA 可作为生殖支原体感染的治疗或预防靶点提供了新的思路。
