The 3rd Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Department of Dermatovenereology, Tianjin Medical University General Hospital, 154 Anshan Rd, Tianjin, 300052, China; Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA.
The 3rd Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China; Department of Microbiology, Immunology and Molecular Genetics, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX, 78229, USA.
Microbes Infect. 2019 Jan-Feb;21(1):50-55. doi: 10.1016/j.micinf.2018.06.003. Epub 2018 Jun 26.
We have previously reported that Chlamydia trachomatis plasmid-encoded Pgp3 is able to neutralize anti-chlamydial activity of human cathelicidin peptide LL-37 by binding to and forming stable complex with LL-37. Besides its microbicidal activity, LL-37 also modulates immune response, including inducing cytokine/chemokine production in fibroblast/epithelial cells and recruitment of inflammatory cells. We now report that LL-37 was significantly induced in the genital tracts of women diagnosed positive for C. trachomatis. Both the LL-37-stimulated IL-6/8 production in human endometrial epithelial cells and the LL-37-induced neutrophil chemotaxis were blocked by Pgp3. Interestingly, although Pgp3 itself alone could not induce cytokines in epithelial cell cells, it did so in neutrophils. Importantly, the Pgp3 proinflammatory activity in neutrophils was significantly enhanced by forming complex with LL-37 although LL-37 alone failed to induce cytokine production in neutrophils. Thus, we have demonstrated that Pgp3 can modulate the proinflammatory activities of LL-37 on epithelial cells by forming stable complex with LL-37 but the Pgp3's own proinflammatory activity on myeloid cells is enhanced by forming the same complex. We hypothesize that Chlamydia may use Pgp3 to both block detrimental inflammation for improving its own fitness in the genital tract epithelial tissue and activate myeloid cell-mediated inflammation for potentially promoting spreading between the hosts, the latter of which may inevitably contribute to the development of inflammatory sequelae such as tubal fibrosis.
我们之前报道过，沙眼衣原体质粒编码的 Pgp3 能够通过与 LL-37 结合并形成稳定的复合物来中和人抗菌肽 LL-37 的抗衣原体活性。除了其杀菌活性外，LL-37 还调节免疫反应，包括在成纤维细胞/上皮细胞中诱导细胞因子/趋化因子的产生和炎症细胞的募集。我们现在报告说，在被诊断为沙眼衣原体阳性的女性生殖道中，LL-37 的表达明显增加。Pgp3 可阻断 LL-37 刺激的人子宫内膜上皮细胞中 IL-6/8 的产生和 LL-37 诱导的中性粒细胞趋化作用。有趣的是，尽管 Pgp3 本身不能诱导上皮细胞中的细胞因子，但它可以在中性粒细胞中诱导。重要的是，尽管 LL-37 本身不能诱导中性粒细胞产生细胞因子，但它与 LL-37 形成复合物后，Pgp3 的促炎活性在中性粒细胞中显著增强。因此，我们已经证明，Pgp3 可以通过与 LL-37 形成稳定的复合物来调节 LL-37 对上皮细胞的促炎活性，但 Pgp3 自身对髓样细胞的促炎活性通过形成相同的复合物而增强。我们假设衣原体可能利用 Pgp3 来阻断有害的炎症，以提高其在生殖道上皮组织中的适应性，同时激活髓样细胞介导的炎症，以促进宿主之间的传播，后者可能不可避免地导致炎症后遗症的发展，如输卵管纤维化。
