Mechanisms of Immune Avoidance by Haemophilus ducreyi

描述（由申请人提供）：软下疳是一种细菌性生殖器溃疡疾病，流行于撒哈拉以南非洲和东亚。对软下疳的病原体杜克雷嗜血杆菌的免疫应答，在清除感染个体的微生物或预防随后的嗜血杆菌方面都不是很有效。ducreyi再次感染。本文所述的三个具体目的旨在利用和扩展软下疳的猪模型，以测试与这种不良免疫应答的机制相关的假设。 目的1评估宿主对H. ducreyi通过检验H. Ducreyi主要引起细胞免疫，这在清除感染细菌方面是无效的。H.将检查从感染病灶分离的杜克雷氏特异性CD 4和CD 8淋巴细胞。在目标2中，细菌对抑制免疫应答的贡献将通过检验H. ducreyi CDT和溶血素毒素通过其对免疫效应细胞的细胞毒性作用阻断免疫发育。这一目的将通过比较接种cdt/hem双突变体和野生型H. ducreyi，同时还评估了与野生型生物体相比，突变体影响的T细胞细胞因子表达和抗原特异性的差异。毒素对免疫反应的具体贡献将通过测试其对鸡蛋溶菌酶的抗体和细胞毒性T细胞的发展的影响来检查。 目的2提出了一个假设，即一个强有力的杀菌抗体反应H。ducreyi将导致更有效地清除感染组织中的微生物，并防止随后的H。ducreyi再感染。 一个H。已经鉴定了作为杀菌抗体靶的杜克雷氏外膜蛋白。该蛋白质将被测试引发针对H的保护性免疫应答的能力。ducreyi。

DESCRIPTION (provided by applicant): Chancroid is a bacterial genital ulcer disease endemic to sub-Saharan Africa and Eastern Asia. The immune response to Haemophilus ducreyi, the etiologic agent of chancroid, is not very effective at either clearing organisms from an infected individual or at preventing subsequent H. ducreyi re-infections. The three specific aims described herein are designed to utilize and extend the swine model of chancroid to test hypotheses that relate to the mechanisms underlying this poor immune response. Aim 1 assesses the host response to H. ducreyi by testing the hypothesis that H. ducreyi elicit predominantly cellular immunity, which is ineffective at clearing the infecting bacteria. The cytokine expression pattern of H. ducreyi specific CD4 and CD8 lymphocytes isolated from infected lesions will be examined. In Aim 2 the bacterial contribution to inhibiting the immune response will be addressed by testing the hypothesis that the H. ducreyi CDT and hemolysin toxins block immunity development through their cytotoxic effect on immune effector cells. This aim will be accomplished by comparing the kinetics and strength of immune development following inoculation with cdt/hem double mutants and wild type H. ducreyi, while also assessing differences in T cell cytokine expression and antigen specificity effected by mutant as compared to wild type organisms. The specific contribution of the toxins on the immune response will be examined by testing their effect on the development of antibody and cytotoxic T cells to hen egg lysozyme. Aim 2 addresses the hypothesis that a vigorous bactericidal antibody response to H. ducreyi would result in more efficient clearing of organisms from infected tissue and prevent subsequent H. ducreyi re infection. An H. ducreyi outer membrane protein that is a target for bactericidal antibody has been identified. This protein will be tested for the ability to elicit a protective immune response to H. ducreyi.