Immunological masking by schistosomes

血吸虫的免疫掩蔽

• 批准号: nhmrc : 290247
• 负责人: Prof Alexander Loukas
• 金额: $ 16.9万
• 依托单位: Queensland Institute of Medical Research
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2004
• 资助国家: 澳大利亚
• 起止时间: 2004-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/immunological-masking-schistosomes/76058
• 关键词: Immunological; masking; schistosomes

Schistosomes are parasitic flukes that survive in the blood vessels of their human hosts for many years. More than 200 million people are infected in developing countries, and Australian travelers to these regions are often infected. As larval schistosomes mature, they undergo physiological changes in the their outer surface, the tegument, and rapidly become refractory to vigorous immune responses. In the 1960's, researchers proposed that schistosomes evade otherwise destructive immune responses by masking their presence through the adsorption of host molecules onto the parasite surface. Intriguingly, most of the molecules adsorbed by the parasite are proteins involved in immune responses, such as MHC and immunoglobulins. In order to understand the molecular basis of schistosome maturation and masking, we recently isolated a protein that binds host IgG-Fc from the surfaces of schistosomes. We hypothesise that masking proteins expressed on the surface of developing parasites interfere with the development of protective immune responses by masking the otherwise susceptible tegument. Moreover, masking proteins are ideal candidate antigens for anti-schistosome vaccines. We now propose to test this hypothesis by identifying schistosome surface proteins that acquire host immune molecules, and isolate the genes encoding these parasite masking proteins. Masking proteins will be identified using protein-based affinity methods and differentially expressed gene- and protein-based methods. Recombinant masking proteins will then be assessed as unmasking vaccines in a mouse model of schistosomiasis. Elucidation of these aims should help to unravel the widely reported enigma of schistosome masking and the long-term survival of the parasite in the human bloodstream. By unmasking these parasites from their host-derived cloak, novel methods of controlling schistosomiasis will be revealed and efforts to develop a vaccine will be greatly accelerated.

血吸虫是寄生的吸虫，在人类宿主的血管中存活多年。发展中国家有超过2亿人受到感染，前往这些地区的澳大利亚游客经常受到感染。随着幼虫血吸虫的成熟，它们的外表面，即被膜经历了生理变化，并迅速对强烈的免疫反应变得难以抵抗。在20世纪60年代，S提出，血吸虫通过吸附宿主分子到寄生虫表面来掩盖它们的存在，从而逃避本来具有破坏性的免疫反应。有趣的是，被寄生虫吸附的大多数分子都是参与免疫反应的蛋白质，如MHC和免疫球蛋白。为了了解血吸虫成熟和掩蔽的分子基础，我们最近从血吸虫表面分离了一种结合宿主免疫球蛋白-Fc的蛋白。我们假设，在发育中的寄生虫表面表达的掩蔽蛋白通过掩蔽原本敏感的被膜来干扰保护性免疫反应的发展。此外，掩蔽蛋白是抗血吸虫疫苗理想的候选抗原。我们现在建议通过鉴定获得宿主免疫分子的血吸虫表面蛋白来检验这一假设，并分离编码这些寄生虫掩蔽蛋白的基因。掩蔽蛋白将使用基于蛋白质的亲和力方法和基于差异表达的基因和蛋白质的方法进行鉴定。然后，将在血吸虫病小鼠模型中评估重组掩蔽蛋白作为非掩蔽疫苗的作用。这些目的的阐明应该有助于解开被广泛报道的血吸虫掩盖之谜以及寄生虫在人类血液中的长期生存。通过揭开这些寄生虫从宿主衍生的斗篷中的面纱，控制血吸虫病的新方法将被揭示出来，开发疫苗的努力将大大加快。