Underlying mechanisms of schistosome/snail compatibility

血吸虫/蜗牛相容性的潜在机制

基本信息

批准号：
6640134
负责人：
CHRISTOPHER JEFFREY BAYNE
金额：
$ 28.3万
依托单位：
OREGON STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1981
资助国家：
美国
起止时间：
1981-09-30 至 2006-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by the applicant): The long-term objectives are to break the cycle of schistosomiasis transmission to humans, and to extend understanding of parasite strategies for survival in immunocompetent hosts. This is important because the occurrence of human schistosomiasis requires successful infection of the intermediate host snail Biomphalaria glabrata, so that interruption of the intra-molluscan stages of the life cycle could break the transmission cycle. Our hypothesis is that, in the early stages of molluscan schistosomiasis, products of the host hemocytes' respiratory burst and counter-defenses of the parasite are the major (but not exclusive) determinants of the parasite's fate. Specific aims are to determine the mechanisms responsible for the resistant and susceptible host phenotypes in the B. glabrata-Schistosoma mansoni PR-I strain host-parasite system, and to identify properties of this and other strains of the parasite that account for differences in infectivity. The distinctive fates of individual parasites in susceptible and resistant strains of host snail may be due to the combined effects of oxygen-independent and of oxygen- and nitrogen-dependent defense pathways of the host. The research will use in vitro models of parasite killing in which enzymes and products of these pathways will be measured and manipulated, gene transcript sequences will be obtained, and transcript levels will be determined in naive and challenged snails. The basis of a cost associated with resistance will be examined, and both proteomic and genomic approaches will be used to extend knowledge of gene products involved in determining compatibility. These studies will be done with both hosts and parasites. Differences in oxygen-independent cytotoxic mechanisms will be examined by both comparative proteomics and differential gene expression analyses. Tests of plausible hypotheses should lead to a better understanding of the mechanisms that lead to successful elimination of the parasite by resistant individuals of the molluscan host, and the means used by parasites to survive and proliferate while confronting the innate immune system of the mollusk. The suggested mechanisms may account for compatibility phenotypes in a broader range of strains and species, and for the recognized 'cost of resistance' in this parasitism.

描述（由申请人提供）：长期目标是打破血吸虫病传播到人类的周期，并扩展对免疫能力宿主生存的寄生虫策略的理解。这很重要，因为人血吸虫病的发生需要成功地感染中间宿主蜗牛生物胶质胶状glabrata，以便中断生命周期的毛内内群落阶段中断可能会破坏传输周期。我们的假设是，在软体动物血吸虫病的早期阶段，寄生虫的主要（但不是独家）决定因素的宿主血细胞呼吸道爆发和反甲的产物。具体目的是确定负责抗性和易感宿主表型的机制，曼氏杆菌菌菌Pr-I菌株宿主寄生虫系统，并识别寄生虫的特性，这些寄生虫的特性涉及感染性差异。宿主蜗牛的敏感和抗性菌株中单个寄生虫的独特命运可能是由于氧无依赖性氧和氧气和氮和氮依赖的防御途径的综合作用。该研究将使用寄生虫杀戮的体外模型，其中将测量这些途径的酶和产品，并操纵这些途径，基因转录序列，并在幼稚和挑战的蜗牛中确定转录水平。将检查与阻力相关的成本的基础，并将使用蛋白质组学和基因组方法来扩展对确定兼容性涉及的基因产物的知识。这些研究将使用宿主和寄生虫进行。比较蛋白质组学和差异基因表达分析，将检查非氧无氧细胞毒性机制的差异。合理假设的测试应使人们更好地理解Molluscan宿主的抵抗个体成功消除寄生虫的机制，以及寄生虫使用的手段在面对Mollusk的先天免疫系统的同时，使用寄生虫来生存和增殖。建议的机制可能解释了在更广泛的菌株和物种中的兼容性表型，以及在这种寄生虫中公认的“抵抗成本”。