Interaction of Neisseria gonorrhoeae with polarized human endocervical epithelial

淋病奈瑟菌与极化人宫颈内膜上皮的相互作用

• 批准号: 8429826
• 负责人: WENXIA SONG
• 金额: $ 17.86万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-10 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8429826
• 关键词: Actins; Acute suppurative arthritis due to bacteria; Adherence; Anatomy; Apical; Bacteria; Blindness; Cell Communication; Cell model; Cells; Cellular Morphology; Clinical; Cytoskeleton; Data; Disease; Ectopic Pregnancy; Epithelial; Epithelial Cells; Epithelium; Female; Future; Genital system; Goals; Gonadal Steroid Hormones; Gonorrhea; HIV; Health; Human; Immune system; Infection; Infertility; Inflammation; Intercellular Junctions; Invaded; Knowledge; Lead; Link; Location; Measures; Modeling; Molecular; Nature; Neisseria gonorrhoeae; Newborn Infant; Patients; Pelvic Inflammatory Disease; Predisposition; Pregnant Women; Preventive; Process; Public Health; Recruitment Activity; Research; Risk; Role; Sexually Transmitted Diseases; Site; Surface; Symptoms; Testing; Therapeutic; Therapeutic Intervention; Time; Tissues; Woman; Women' s Health; base; cellular microvillus; in vitro Model; in vivo; innovation; men; monolayer; novel; pathogen; polarized cell; reproductive; response; tool

DESCRIPTION (provided by applicant): Neisseria gonorrhoeae, an obligate human pathogen, causes a common sexually transmitted infection, gonorrhea. While gonococci (GC) cause symptomatic inflammation of the genital tissue in men, GC infections in women are often asymptomatic. The silent infection allows the bacteria to disseminate, which can lead to pelvic inflammatory disease (PID), a leading cause of ectopic pregnancy and infertility. Disseminated gonococcal infection (DGI) may give rise to septic arthritis. Pregnant women can transmit the infection to newborns, causing blindness. Furthermore, silent GC infections increase the susceptibility of patients to HIV. These complications clearly make gonorrhea a significant public health problem, particularly in women. Our long-term goal is to delineate the cellular and molecular mechanisms underlying GC infections in women. The research on the mechanistic basis of GC infection in the female reproductive tract has been hindered by a lack of effective research models. Previous studies have mainly relied on nonpolarized epithelial cells. Because the surface of the female reproductive tract is protected by a layer of polarized epithelial cells, these data can only be applicable to clinical infections f GC interacts with polarized and nonpolarized epithelial cells in the same manner. The central hypothesis to be tested in this proposal is that GC interactions with polarized epithelial cells differ significantly from GC interactions with nonpolarized cells. We have formulated this hypothesis based on our strong preliminary data that show that the actin cytoskeleton is excluded from GC adherent sites at the apical surface of polarized epithelial cells, rather than being recruited to the adherent sites as seen in nonpolarized cells. The goal of this proposal is to define the differences between GC interactions with polarized and nonpolarized endocervical epithelial cells and to investigate the mechanistic links between the unique interaction of GC with the polarized cells and GC infection. To reach this goal, we will use polarized primary and virally immortalized human endocervical epithelial cells to pursue two aims: 1) to examine the nature of GC interactions with polarized endocervical epithelial cells and 2) to investigate how the unique interactions of GC with polarized endocervical epithelia lead to GC infection. Polarized primary and virally immortalized endocervical epithelial cell models will enable us to examine GC-epithelia interactions under the conditions that mimic the in vivo conditions of the female reproductive tract and to discover novel mechanisms that are specific for GC infections in women. Our strong preliminary studies demonstrate the potential of the proposed studies to expand the existing paradigms of GC infections. New mechanistic knowledge derived from the proposed studies will help to generate new strategies for interventions and therapies for gonorrhea and other sexually transmitted infections

描述（由申请人提供）：淋病奈瑟菌，一种专性人类病原体，引起常见的性传播感染，淋病。虽然淋球菌（GC）引起男性生殖器组织的症状性炎症，但女性GC感染通常无症状。这种无声的感染使细菌传播，这可能导致盆腔炎（PID），这是异位妊娠和不孕症的主要原因。播散性淋球菌感染（DGI）可引起脓毒性关节炎。孕妇可以将感染传染给新生儿，导致失明。此外，沉默的GC感染增加了患者对HIV的易感性。这些并发症显然使淋病成为一个重大的公共卫生问题，特别是在妇女中。我们的长期目标是阐明女性GC感染的细胞和分子机制。 由于缺乏有效的研究模型，对女性生殖道GC感染机制的研究一直受到阻碍。以前的研究主要依赖于非极化上皮细胞。由于女性生殖道表面受到一层极化上皮细胞的保护，因此这些数据仅适用于GC以相同方式与极化和非极化上皮细胞相互作用的临床感染。在这个建议中要测试的中心假设是，GC与极化上皮细胞的相互作用显着不同的GC与非极化细胞的相互作用。我们已经制定了这一假设的基础上，我们强有力的初步数据表明，肌动蛋白细胞骨架被排除在极化上皮细胞的顶端表面的GC粘附位点，而不是被招募到粘附位点中看到的非极化细胞。 本提案的目的是确定GC与极化和非极化宫颈上皮细胞之间的相互作用的差异，并调查GC与极化细胞和GC感染的独特相互作用之间的机制联系。为了达到这一目标，我们将使用极化的原代和病毒永生化的人宫颈内上皮细胞来追求两个目标：1）检查GC与极化的宫颈内上皮细胞相互作用的性质和2）研究GC与极化的宫颈内上皮细胞的独特相互作用如何导致GC感染。 极化的原代和病毒永生化的宫颈上皮细胞模型将使我们能够在模拟女性生殖道体内条件的条件下研究GC-上皮细胞的相互作用，并发现女性GC感染的特异性新机制。我们强有力的初步研究表明，拟议的研究扩大现有的GC感染的范例的潜力。从拟议的研究中获得的新的机制知识将有助于产生淋病和其他性传播感染的干预和治疗的新策略