Host response to Chlamydia genital infection in the male

男性对衣原体生殖器感染的宿主反应

• 批准号: 6984772
• 负责人: Roger G Rank
• 金额: $ 34.67万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6984772
• 关键词: chlamydial disease; communicable disease transmission; cytokine; female reproductive system disorder; gender difference; guinea pigs; immune response; immunity; immunization; laboratory rabbit; male reproductive system disorder; reproductive system infection; semen; sexually transmitted diseases

DESCRIPTION (provided by applicant): Genital infection with Chlamydia trachomatis remains the most prevalent bacterial sexually transmitted disease, resulting in significant morbidity in the female in the form of pelvic inflammatory disease, involuntary infertility, and ectopic pregnancy. Consequently, the major research emphasis has been directed toward the understanding of the disease processes and protective immune response in the female with the ultimate goal of developing a vaccine to protect against upper genital tract disease. However, a vaccine would also be used to protect males against disease. Immunizing males would have the obvious advantage of reducing the infectious dose for females and thereby enhance the protective capabilities of the vaccine in the female. Other than epidemiological or diagnostic studies, there have been only a handful of reports addressing the host response to chlamydial infections in the male, and virtually nothing is known about the local immune response in the male genital tract to any sexually transmitted agent. Other than primates, the only animal model in which the course of infection in males following urethral inoculation has been studied is the guinea pig infected with the Chlamydia psittaci agent of guinea pig inclusion conjunctivitis (GPIC), a natural parasite of the guinea pig. Of major interest was our observation that the majority of male guinea pigs recovered from a primary GPIC infection were completely immune to reinfection for long periods of time, whereas female guinea pigs were 100% susceptible to reinfection over the same time frame, suggesting that there is some aspect of the immune response in males which provides a better protective response. We have also demonstrated that sexual transmission from males to females can be accomplished reliably in a predictable time period. Of major importance was our observation that the females infected by sexual transmission shed chlamydiae for a significantly shorter period of time than any animal infected artificially with a comparable dose. This suggested that factors in semen may enhance the host response in the female genital tract. Therefore, the major objective of this proposal is to explore the innate and adaptive immune responses in the male urethra and to test the hypothesis that factors in semen may affect the course of the infection in the female. The Specific Aims will be 1) to characterize the immune response in the male urethra in guinea pigs to a primary GPIC infection and to reinfection, 2) to determine the basis for long-term sterile immunity following a primary infection in contrast to partial immunity resulting from artificial immunization, and 3) to determine the mechanism of abbreviated infection in female guinea pigs infected with GPIC by sexual transmission.

描述（由申请人提供）：沙眼衣原体的生殖器感染仍然是最普遍的细菌性传播疾病，导致女性以骨盆炎症性疾病，非自愿性不育症和异位妊娠的形式显着发病。因此，主要的研究重点是针对女性疾病过程和保护性免疫反应的理解，其最终目的是开发一种疫苗以防止上生殖器疾病。但是，疫苗也将用于保护雄性免受疾病的侵害。免疫性男性将具有明显的优势，即减少女性感染剂量，从而增强女性疫苗的保护能力。除流行病学或诊断研究外，只有少数报道涉及男性对衣原体感染的反应，几乎没有关于男性生殖道对任何性传播药物的局部免疫反应的了解。除灵长类动物外，还研究了尿道接种后雄性感染的唯一动物模型是被豚鼠内调结膜炎（GPIC）感染的豚鼠，这是豚鼠的天然寄生虫。我们观察到的是，从原发性GPIC感染中回收的大多数雄性豚鼠长期以来完全免疫可再感染，而雌性豚鼠则100％容易在相同的时间范围内再感染，这表明在男性中有更好的保护反应的免疫反应，这提供了更好的保护反应。我们还证明，可以在可预测的时间段可靠地完成从男性到女性的性传播。至关重要的是，我们的观察是，被性传播棚感染的女性在一段时间内比人为以类似剂量的人为感染的动物短时间短。这表明精液中的因素可能会增强女性生殖道中的宿主反应。因此，该提案的主要目的是探索男性尿道中的先天和适应性免疫反应，并检验以下假设：精液中的因素可能会影响女性感染的过程。具体目的是1）表征豚鼠中雄性尿道的免疫反应对主要的GPIC感染并恢复感染，2）确定主要感染后长期无菌免疫的基础，与人工免疫相比，部分免疫，以及通过abbreverifed abbreveriated gp gp gp gp猪的传播机制。