PDF(Pubmed)
Abstract：
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. IMPORTANCE 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.
摘要：
生殖支原体是引起泌尿生殖道感染的原核微生物。生殖M.粘附蛋白（MgPa）对于生殖M.附着和随后侵入宿主细胞至关重要。我们先前的研究证实亲环蛋白A(CypA)是MgPa的结合受体,并且MgPa-CypA相互作用可导致炎性细胞因子的产生。在这项研究中,我们发现，重组MgPa（rMgPa）可以抑制CaN-NFAT信号通路以降低IFN-γ的水平，Jurkat细胞中的IL-2、CD25和CD69通过与CypA受体结合。此外，rMgPa抑制IFN-γ的表达，原代小鼠T细胞中的IL-2、CD25和CD69。同样，rMgPa增强了这些T细胞活化相关分子在CypA-siRNA转染细胞和CypA-/-小鼠原代T细胞中的表达。这些发现表明rMgPa通过下调CypA-CaN-NFAT途径抑制T细胞活化,结果，充当免疫抑制剂。重要性生殖道支原体是一种性传播细菌，可与其他感染共同感染，并在男性中引起非淋菌性尿道炎，宫颈炎,盆腔炎,早产,和女性的异位妊娠。生殖支原体的粘附蛋白（MgPa）是生殖支原体复杂致病性的主要毒力因子。这项研究证明，MgPa可以与宿主细胞亲环蛋白A（CypA）相互作用，并通过抑制钙调磷酸酶（CaN）磷酸化和NFAT核易位来阻止T细胞活化，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作为生殖支原体感染的治疗或预防靶点提供了新的思路。
