Immunological masking by schistosomes

血吸虫是一种寄生的吸虫，可以在人类宿主的血管中存活多年。发展中国家有超过2亿人被感染，前往这些地区的澳大利亚游客经常被感染。当幼虫成熟时，它们的外表面（被皮）发生生理变化，并迅速变得难以抵抗强烈的免疫反应。在20世纪60年代，研究人员提出，血吸虫通过在寄生虫表面吸附宿主分子来掩盖它们的存在，从而逃避其他破坏性的免疫反应。有趣的是，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出一种结合宿主IgG-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其他敏感的被皮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的理想候选抗原。我们现在提议通过鉴定获得宿主免疫分子的血吸虫表面蛋白来验证这一假设，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揭面罩疫苗的作用。阐明这些目标应该有助于解开广泛报道的血吸虫掩蔽之谜和寄生虫在人类血液中的长期生存。通过揭开这些寄生虫来自宿主的外衣，将揭示控制血吸虫病的新方法，并将大大加快研制疫苗的努力。

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.