CYTOKINE NETWORK IN CHLAMYDIAL DISEASE

描述(改编自申请人的摘要)：在女性中， 沙眼衣原体感染的表现包括无症状的宫颈炎症 到盆腔炎、不孕不育和异位妊娠。变体 研究结果表明，人类在宿主易感性方面表现出异质性 衣原体病。基因对疾病易感性的影响得到了支持 通过在人类和实验动物模型中的流行病学研究， 感染。候选人已经证实，三个人之间存在真正的差异 关于衣原体生殖器分解的基因定义的小鼠品系 肠道感染和病理性后遗症的发展。尽管如此 不同，大量数据显示它们的获得性免疫反应是 Th1表型的类似-CD4T细胞是恢复的关键 衣原体感染。相比之下，比较在 感染的第一周显示早期细胞和 细胞因子反应介体。这项建议涉及使用固有的 作为检测细胞因子的工具，这些品系的小鼠存在差异 衣原体疾病发病机制中的重要调控途径。这个 细胞因子反应的不同模式在不同人群中的意义 这三种菌株将用基因缺陷的小鼠进行进一步的研究 特定的细胞因子介体。该提案的具体目标包括：1) 确认肿瘤坏死因子-α和中性粒细胞在糖尿病早期控制中的作用 衣原体感染及其在肺炎发生发展中的作用 慢性病理学；2)描述其他促炎因素的作用 细胞因子(白介素1和白介素6)和选择性趋化因子对宿主的作用 防御和免疫病理学；3)测定是否有不同的动力学 下调的细胞因子，转化生长因子-β和白介素10，影响病程和 衣原体生殖道感染的转归。细胞因子的测定 促进组织损伤的反应模式与导致良性反应的反应模式 感染的解决是关于发展一种 安全有效的衣原体疫苗。

DESCRIPTION (Adapted from the Applicant's Abstract): In women, the manifestations of C. trachomatis infection range from asymptomatic cervicitis to pelvic inflammatory disease, infertility, and ectopic pregnancy. Variations in outcomes suggest humans exhibit heterogeneity in host susceptibility to chlamydial disease. A genetic influence on disease susceptibility is supported by epidemiological studies in humans, and in animal models of experimental infection. The candidate has confirmed that true differences exist among three genetically defined strains of mice as regards resolution of chlamydial genital tract infection and the development of pathological sequelae. Despite these differences, extensive data reveal their acquired immune responses to be similar - CD4+ T cells of the Th 1 phenotype are critical to recovery from chlamydial infection. In contrast, comparisons of responses active during the first week of infection reveal significant differences in early cellular and cytokine response mediators. This proposal involves using the inherent differences present in these strains of mice as a tool for examining cytokine regulatory pathways important in chlamydial disease pathogenesis. The significance of the different patterns of cytokine responses determined among the three strains will be further explored with mice genetically deficient in specific cytokine mediators. Specific aims of the proposal include: 1) confirmation of the role of TNF-alpha and of neutrophils in early control of chlamydial infection and determination of their role in the development of chronic pathology; 2) delineation of the contribution of other proinflammatory cytokines (interleukin-1 and interleukin-6) and of select chemokines to host defense and immunopathology; 3) determination if different kinetics of the downregulatory cytokines, TGF-beta and interleukin-10, influence the course and outcome of chlamydial genital tract infection. A determination of cytokine response patterns that promote tissue damage from those that result in benign resolution of infection is an important goal as regards the development of a safe and effective chlamydial vaccine.