Abstract：
Chlamydia trachomatis infection is the leading cause of bacterial urogenital infection and has been demonstrated to drive inflammation and scarring of the reproductive tract. Recent studies have identified key triggers of proinflammatory adaptive immune responses driven by innate leukocytes and epithelia driving immunopathology. Utilizing chimeric mouse models, we investigated the definitive source and role of IL17 and IL17 signalling receptors during early Chlamydia muridarum infection of the female urogenital tract. Bone marrow transplants from wild-type (WT) and IL17A-/- mice to recipients demonstrated equivocal infection kinetics in the reproductive tract, but interestingly, adoptive transfer of IL17A-/- immune cells to WT recipients resulted in no infertility, suggesting a haematopoietic (as opposed to tissue) source of IL17 driving immunopathology. To further delineate the role of IL17 in immunopathology, we infected WT and IL17 receptor A (IL17RA)-/- female mice and observed a significant reduction in immunopathology in IL17RA-/- mice. WT bone marrow transplants to IL17RA-/- recipient mice prevented hydrosalpinx, suggesting signalling through IL17RA drives immunopathology. Furthermore, early chemical inhibition of IL17 signalling significantly reduced hydrosalpinx, suggesting IL17 acts as an innate driver of disease. Early during the infection, IL17 was produced by γδ T cells in the cervico-vagina, but more importantly, by neutrophils at the site of infertility in the oviducts. Taken together, these data suggest innate production of IL17 by haematopoietic leukocytes drives immunopathology in the epithelia during early C. muridarum infection of the female reproductive tract.
摘要：
沙眼衣原体感染是细菌性泌尿生殖道感染的主要原因，并已被证明可引起生殖道的炎症和疤痕。最近的研究已经确定了由先天白细胞和上皮驱动免疫病理学驱动的促炎适应性免疫应答的关键触发因素。利用嵌合小鼠模型，我们调查了女性泌尿生殖道早期鼠衣原体感染过程中IL17和IL17信号受体的确切来源和作用。从野生型（WT）和IL17A-/-小鼠到受体的骨髓移植在生殖道中表现出模棱两可的感染动力学，但有趣的是,将IL17A-/-免疫细胞过继转移至WT受体不会导致不育，提示IL17驱动免疫病理学的造血（相对于组织）来源。为了进一步描述IL17在免疫病理学中的作用，我们感染了WT和IL17受体A（IL17RA）-/-雌性小鼠，并观察到IL17RA-/-小鼠的免疫病理学显着降低。WT骨髓移植到IL17RA-/-受体小鼠可预防输卵管积水，提示通过IL17RA的信号驱动免疫病理学。此外，IL17信号的早期化学抑制显着减少输卵管积水，表明IL17是疾病的先天驱动力。在感染早期,IL17由宫颈阴道中的γδT细胞产生，但更重要的是,由输卵管不孕症部位的嗜中性粒细胞引起。一起来看,这些数据表明,在女性生殖道早期鼠尾草感染期间,由造血白细胞产生的固有IL17驱动上皮的免疫病理学.
