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Gonococcal Inflammatory Immune Responses

淋球菌炎症免疫反应

基本信息

批准号：
7760941
负责人：
MICHAEL W RUSSELL
金额：
$ 19.61万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-02-01 至 2013-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7760941
关键词：
Acute Antibiotic Resistance Antibody Formation Antigenic Variation Antigens Area Bacteria Blood CD4 Positive T Lymphocytes CXC Chemokines Cell secretion Cells Centers for Disease Control and Prevention (U.S.)Communicable Diseases Complement Comprehension Data Defense Mechanisms Development Diagnostic Disease Ectopic Pregnancy Exudate Female Future Generations Genital system Gonorrhea Health Sciences Helper-Inducer T-Lymphocyte Human Immune Immune response Immune system Immunity Immunology In Vitro Incidence Infection Infertility Inflammatory Inflammatory Response Interferons Interleukin Receptor Interleukin-12 Interleukin-17 Interleukin-4 Interleukin-6 Interleukins Intervention Knock-out Lead Life Lymphoid Mediating Modeling Mononuclear Mus Neisseria gonorrhoeae Neutrophil Infiltration Outcome Pathway interactions Pelvic Inflammatory Disease Phagocytes Play Probability Production Recruitment Activity Relative (related person)Reporting Reproductive Health Resistance Risk Role Secondary to Serum Services Severities Signal Transduction Site Specimen Testing Th1 Cells Th2 Cells Tissues United States Universities Ursidae Family Vaccines Vagina Wild Type Mouse Woman congenic cytokine genital secretion improved in vivo interleukin-22 interleukin-23 male mouse model neutrophil novel novel strategies pathogen public health relevance receptor response

项目摘要

DESCRIPTION (provided by applicant): This exploratory R21 application will investigate the significance of the newly described "Th17 axis of immunity" in a mouse model of vaginal gonococcal infection. The objectives are to determine whether Neisseria gonorrhoeae can induce the development of Th17 cells and to test the hypothesis that signaling through the interleukin (IL)-17 receptor is important in the elicitation of the innate immune response. Th17 cells, which produce IL-17, have been shown to play a major role in innate immune/inflammatory responses and in the elicitation of the neutrophil influx in response to mucosal infections. N. gonorrhoeae, the agent of gonorrhea, typically induces a neutrophil influx into the site of infection and the presence in genital secretions of gonococci associated with neutrophils is a classic diagnostic criterion. Like other pathogens, N. gonorrhoeae interacts with host tissues to elicit responses that favor its survival, and the natural infection does not induce protective immunity against repeated infection. It has therefore been suggested that N. gonorrhoeae actively interferes with the development of adaptive immune responses, and it is hypothesized that the elicitation of Th17 cells contributes to this. The Specific Aims are: (1) To evaluate the ability of N. gonorrhoeae to induce the development of Th17 cells and the production of key cytokines in mouse cells in vitro and in vivo, and in human blood mononuclear cells in vitro; (2) To compare the responses of normal wild- type and IL-17 receptor-deficient mice to vaginal challenge with N. gonorrhoeae in order to determine whether signalling through this receptor is critical in the recruitment of neutrophils and in deflecting adaptive immune responses. Elucidation of this novel pathway of the host response to N. gonorrhoeae will greatly improve comprehension of the immuno-pathogenic mechanisms of gonococcal infection and facilitate the development of new interventions against gonorrhea, for which there is a demonstrable need. PUBLIC HEALTH RELEVANCE: Gonorrhea is the second-most-frequent, notifiable infectious disease in the United States and the CDC reports over 300,000 cases in recent years [59], although the true incidence is believed to be double that figure; world- wide incidence is estimated to be over 60 million new infections per year [60]. Women bear the brunt of the infection which can lead to serious reproductive health problems including pelvic inflammatory disease, infertility, and risk for ectopic pregnancy, and while it is well known that gonorrhea does not generate immunity to repeated infection, no vaccines exist to control it and antibiotic resistance is spreading. This proposal will apply important new findings from the field of immunology to determine the way in which the immune system interacts with the gonococcus bacterium, an area that is poorly understood at present.

描述（由申请方提供）：该探索性R21申请将研究新描述的“Th 17免疫轴”在阴道淋球菌感染小鼠模型中的意义。目的是确定淋病奈瑟菌是否可以诱导Th 17细胞的发育，并检验通过白细胞介素（IL）-17受体的信号传导在引发先天性免疫应答中的重要性这一假设。产生IL-17的Th 17细胞已被证明在先天免疫/炎症反应中以及在响应于粘膜感染引起中性粒细胞流入中起主要作用。N.淋病病原体淋病通常诱导中性粒细胞流入感染部位，并且生殖器分泌物中存在与中性粒细胞相关的淋球菌是经典的诊断标准。与其他病原菌一样，N.淋病与宿主组织相互作用以引起有利于其存活的反应，并且自然感染不会诱导针对重复感染的保护性免疫。因此，有人建议，N。淋病主动干扰适应性免疫应答的发展，并且假设Th 17细胞的激发对此有贡献。具体目的是：（1）评价N.（2）比较正常野生型和IL-17受体缺陷型小鼠对淋病奈瑟菌阴道攻击的反应。淋病，以确定通过该受体的信号传导是否在中性粒细胞的募集和在偏转适应性免疫应答中是关键的。阐明了这一新的途径的主机响应N。淋病将极大地提高对淋球菌感染的免疫致病机制的理解，并促进抗淋病的新干预措施的开发，这是一个明显的需求。公共卫生关系：淋病是美国第二常见的应报告的传染病，CDC近年来报告了超过30万例病例[59]，尽管真实发病率被认为是该数字的两倍;全球发病率估计每年超过6000万例新感染[60]。妇女首当其冲的感染，这可能导致严重的生殖健康问题，包括盆腔炎，不孕不育和异位妊娠的风险，虽然众所周知，淋病不会产生免疫力，反复感染，没有疫苗存在，以控制它和抗生素耐药性正在蔓延。该提案将应用免疫学领域的重要新发现来确定免疫系统与淋球菌细菌相互作用的方式，这是目前知之甚少的领域。