Unraveling the mechanisms of cell-mediated Chlamydia systemic dissemination.

揭示细胞介导的衣原体系统传播的机制。

• 批准号: 10517514
• 负责人: Vjollca H Konjufca
• 金额: $ 21.62万
• 依托单位: SOUTHERN ILLINOIS UNIVERSITY CARBONDALE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-11-01 至 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10517514
• 关键词: Animals; Antibodies; Automobile Driving; CCL1 gene; CCL19 gene; CCL21 gene; CCL8 gene; CCR8 gene; CD8-Positive T-Lymphocytes; Cell Migration Inhibition function; Cells; Cervicitis; Characteristics; Chlamydia; Chlamydia Infections; Chlamydia muridarum; Chlamydia trachomatis; Circulation; Common iliac lymph node; Cytolysis; Development; Ectopic Pregnancy; Endophthalmitis; Epithelial Cells; Equilibrium; Event; Excision; Exhibits; Female; Fetus; Gastrointestinal tract structure; Genomics; HIV; Health; Human; Human Papillomavirus; Immunity; Immunobiology; Immunoglobulin G; In Situ; Infant; Infection; Infertility; Inflammatory; Internal Migrations; Knowledge; Life; Macrophage; Malignant neoplasm of cervix uteri; Mediating; Modeling; Mus; Neonatal; Pathogenesis; Pathology; Pelvic Inflammatory Disease; Phase; Phenotype; Pneumonia; Pregnant Women; Proliferating; Reporting; Reproductive Tract Infections; Risk; Role; Salpingitis; Serum; Sexual Transmission; Sexually Transmitted Diseases; Signal Transduction; Site; Spleen; Synteny; T-Lymphocyte; Testing; Tissues; Transgenic Mice; Vacuole; Vagina; Woman; Work; antagonist; cell motility; cell type; chemokine; chemokine receptor; chronic pelvic pain; embryo/fetus antigen; gastrointestinal infection; improved; migration; monocyte; mouse model; mucosal vaccine; pathogen; pathogenic bacteria; permissiveness; reproductive tract; sphingosine 1-phosphate; tissue tropism; transmission process; tubal infertility; vaccine development; young woman

PROJECT SUMMARY/ABSTRACT Recently WHO estimated that more than 1 million new STIs are acquired daily. In 2016 of about 376 million new STIs, 127 million were caused by Chlamydia. In the US, Chlamydia continues to be a leading cause of STIs, with 1.7 million cases of approximately 2.3 million STIs reported in 2017. Chlamydial infections in women may result in cervicitis, salpingitis, pelvic inflammatory disease, causing infertility or life-threatening ectopic pregnancy. Moreover, chlamydial STIs in women are associated with increased transmission of HIV and an increased risk of cervical cancer when co-infected with HPV. In spite of great efforts, the development of mucosal vaccines that target Chlamydia has been unsuccessful. In the mouse model of infection, Chlamydia spreads from the female reproductive tract (FRT) to infect and persist in the gastro-intestinal tract (GIT). GIT infections with Chlamydia also occur in humans. In mice, following FRT infection Chlamydia muridarum (Cm) disseminates systemically in stages, by first infecting the FRT-draining iliac lymph nodes (ILNs), then the spleen, and the GIT. Cm dissemination relies on carriage by migrating host cells. Inhibition of cell migration in CCR7-/- mice or in mice treated with FTY720 diminishes or abrogates Cm spread to the spleen and the GIT. Moreover, removal of the spleen drastically reduces Cm infection of the GIT. Most importantly, removal of the spleen hinders Cm ascension in the upper FRT and abrogates the FRT pathology. We hypothesize that the spleen is a permissive site for Cm proliferation and that circulating infected cells contribute to Cm spread to the upper FRT. Therefore, the knowledge gained from the proposed work will improve our understanding of FRT immunobiology, cell migration, Chlamydia pathogenesis, and will be important for the development of vaccines and therapies to target this pathogen.

项目摘要/摘要 最近，谁估计每天收购超过100万个新的传播感染。 2016年约3.76亿 新的性传播感染，1.27亿是由衣原体引起的。在美国，衣原体仍然是 性传播疾病，2017年报告约有170万例性传播感染性传播疾病。 可能导致宫颈炎，盐炎，盆腔炎症性疾病，导致不孕或威胁生命的异位 怀孕。此外，妇女的衣原体性传播疾病与艾滋病毒的传播增加有关 与HPV共同感染时，会增加宫颈癌的风险。尽管做出了巨大的努力，但 靶向衣原体的粘膜疫苗没有成功。在小鼠感染模型中 从女性生殖道（FRT）传播，以感染并持续存在于胃肠道（GIT）中。 git 对衣原体的感染也发生在人类中。在小鼠中，在FRT感染之后 通过首先感染dradantain dra的iLiac淋巴结（ILN），然后在阶段进行全身传播 脾脏和git。 CM传播通过迁移宿主细胞来依赖运输。抑制细胞迁移 CCR7 - / - 小鼠或用FTY720处理的小鼠减少或消除CM扩散到脾脏和GIT。 此外，脾脏的去除大大减少了GIT的CM感染。最重要的是，去除 脾脏阻碍了上FRT中的CM升高，并消除了FRT病理学。我们假设 脾脏是CM增殖的宽松部位，循环感染细胞有助于CM扩散到 上frt。因此，从拟议的工作中获得的知识将改善我们对FRT的理解 免疫生物学，细胞迁移，衣原体发病机理，对于疫苗的开发至关重要 和靶向这种病原体的疗法。