Cellular Trafficking to Inflamed Female Genital Mucosa

沙眼衣原体是一种专性细胞内细菌，导致大多数病例 细菌性传播疾病。美国每年发生300万例新病例，其中大多数 无症状且未接受治疗。未经治疗、持续感染或再感染会导致盆腔感染 炎症性疾病、异位妊娠和输卵管不孕，给医疗行业造成了数十亿美元的损失 每年1美元。对沙眼衣原体的免疫反应是生殖的部分原因。 功能障碍。趋化因子CXCL13在免疫反应过程中在组织内分泌，是 对于在组织内组装和组织淋巴聚集物很重要。CXCL13只是暂时的 由非病变组织分泌，并持续分泌，一直被认为是维持 异位淋巴样结构，表明存在持续的免疫反应。有趣的是， 输卵管内出现异位淋巴集合体可诊断为输卵管炎。 它先于输卵管性不孕症。我们发现上生殖道(UGT)组织感染C. 沙眼衣原体诱导输卵管及其分泌物中CXCL13的表达 受黄体酮的调节。CXCL13分泌降低感染后炎症程度 在小鼠的UGT内，同时不干扰细菌的清除。我们假设CXCL13吸引了 CXCR5+细胞到UGT，这个细胞对于预防女性UGT的炎症是必不可少的。 干扰这种相互作用会导致炎性T细胞的持续募集，并可能导致 不孕不育。我们提出以下具体目标来检验这一假说：1)调查 CXCL13-CXCR5轴在体内调节炎症中的作用2)确定C. 沙眼衣原体在人UGT细胞内诱导CXCL13。3)评价孕酮在调控中的作用程度 感染后CXCL13的表达。我们将利用活体小鼠实验来鉴定表型& CXCR5+细胞的功能。此外，我们还将研究宿主-病原体与人UGT上皮细胞的相互作用 细胞用实时荧光定量聚合酶链式反应、酶联免疫吸附试验和NFkB通路分析。CXCL13可能是一种 衣原体生殖器感染后的炎症。对CXCL13分泌的洞察将影响公众健康 并通过帮助开发治疗方法来预防输卵管性不孕症，从而促进美国妇女的福利。

Chlamydia trachomatis is an obligate intracellular bacterium responsible for causing the most cases of bacterial sexually transmitted disease. Three million new cases occur in the US each year and the majority are asymptomatic and not treated. Untreated, persistent infection or reinfection results in pelvic inflammatory disease (PID), ectopic pregnancy & tubal infertility and cost the health care industry billions of dollars annually. The immune response against C. trachomatis is in part responsible for the reproductive dysfunction. The chemokine, CXCL13, is secreted within tissues during an immune response and is important for assembling and organizing lymph aggregates within tissues. CXCL13 is only temporarily secreted by non-diseased tissues and continual secretion has been postulated to maintain the presence of ectopic lymphoid structures and indicates the presence of an ongoing immune response. Intriguingly, the presence of ectopic lymphoid aggregates within fallopian tubes is diagnostic for salpingitis, a condition which precedes tubal infertility. We found that infection of upper genital tract (UGT) tissue with C. trachomatis induces expression of CXCL13 which is not routinely present in fallopian tubes and its secretion is modulated by progesterone. CXCL13 secretion reduces the magnitude of post-infection inflammation within the murine UGT while not interfering with bacterial elimination. We hypothesize that CXCL13 attracts a CXCR5+ cell to the UGT and this cell is indispensable for preventing inflammation in the female UGT. Interference with this interaction causes continual recruitment of inflammatory T cells and could contribute to infertility. We propose the following specific aims to test this hypothesis, 1) Investigate the extent of the CXCL13-CXCR5 axis in regulating inflammation in vivo. 2) Identify the mechanism(s) whereby C. trachomatis induces CXCL13 within human UGT cells. 3) Evaluate the extent of progesterone in modulating CXCL13 expression after infection. We will employ in vivo mouse experiments to identify the phenotype & function of CXCR5+ cells. Also, we will investigate host-pathogen interaction with human UGT epithelial cells using real-time PCR, ELISA assays and NFkB pathway analysis. CXCL13 may be a regulator of inflammation following a Chlamydia genital infection. Insight into CXCL13 secretion will impact public health and the welfare of women in the US by aiding the development of therapeutics to prevent tubal infertility.