DEVELOPMENTAL ADAPTATIONS OF TRYPANOSOMA CRUZI TO THE VERTEBRATE IMMUNE SYSTEM

克氏锥虫对脊椎动物免疫系统的发育适应

• 批准号: 4688413
• 负责人: A SHER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4688413
• 关键词: Trypanosoma cruzi; affinity chromatography; complement; complement pathway; complementary DNA; genetic library; host organism interaction; membrane activity; microorganism immunology; tissue /cell culture; trypanosomiasis

In this project, we have been studying developmental adaptations of Trypanosoma cruzi to the vertebrate host, and in particular, surface membrane changes occuring during the morphogenesis of epimastigotes (vector stage) to metacyclic trypomastigotes (vertebrate stage). During the report period, we continued to investigate the mechanism by which metacyclic trypomastigotes become resistant to lysis by the alternative pathway of complement (ACP). Studies with purified complement components revealed that in comparison to epimastigotes, metacyclic trypomastigotes bind minimal amounts of Factor B, an essential co-factor in the ACP. In contrast, to the findings obtained with other systems, binding of the regulatory component H was equivalent in activating epimastigotes and non-activating metacyclic trypomastigotes. Enzyme treatment studies suggested that the incapacity of metacyclic trypomastigotes to activate the ACP was due to their elaboration of pronase and tunicamycin sensitive molecules. In related studies, we investigated the expression of a 72,000 MN glycoprotein (GP72) (previously shown by us to be the acceptor for C3 on epimastigotes) on insect and culture derived metacyclic trypomastigotes. Using monoclonal antibodies, GP72 was detected on the surface of insect metacyclics but was not found on culture generated organisms. Since by surface labelling and immunoprecipitation we were able to detect the molecule on this stage, it apparently is modified and expresses fewer epitopes accessible to antibody binding on intact parasites than its equivalent on epimastigotes. Finally, using rabbit anti-idiotypic antibodies directed against an anti-GP72 monoclonal antibody, we were able to raise an antibody response against carbohydrate determinants on the GP72 molecule in mice, rabbits and guinea pigs.

在这个项目中，我们一直在研究发育适应