Mansonella perstans in vitro culture system and RAG2IL-2Rgamma-deficient C57BL/6 mouse model of filariasis: Novel approaches to elucidate Mansonella perstans biology and potential treatment strategies

曼森氏菌体外培养系统和 RAG2IL-2Rgamma 缺陷型 C57BL/6 丝虫病小鼠模型：阐明曼森氏菌生物学和潜在治疗策略的新方法

• 批准号: 405531500
• 负责人: Dr. Manuel Ritter
• 金额: --
• 依托单位: Department of Microbiology and Parasitology
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/405531500?language=en
• 关键词: Mansonella; perstans; vitro; culture; system

The filarial nematode Mansonella perstans (M. perstans) is one of the most prevalent human parasites in sub-Saharan Africa and it is estimated that around 110 million people are infected. Unlike lymphatic filariasis or onchocerciasis, M. perstans infections cause no distinct pathology and only mild symptoms like subcutaneous swellings, skin rashes and pleuritis have been documented. Nevertheless, there are indications that M. perstans influences susceptibility and disease course of other infections implying that there could be heath risks in endemic communities. Research on M. perstans has been hindered by the inability to obtain adult worms and our current studies have resolved this issue by developing two novel approaches: 1) an in vitro culture system to develop M. perstans worms and 2) expansion of our filarial mouse model using the RAG2IL-2Rgamma-deficient C57BL/6 laboratory strain. The former allows long-term maintenance and development of M. perstans filariae. Thus, we will address unknown facets of M. perstans biology using immune-staining and fluorescent microscopy to decipher moulting behaviour, distribution and migration of Wolbachia, and anatomical features that are perhaps unique to this filariae. Moreover, our recent studies show the potential of RAG2IL-2Rgamma-deficient C57BL/6 mice to host filariae pathogenic to man. Thus, this mouse model will provide a novel platform to decipher aspects of host-parasite relationships and through a series of adoptive transfer experiments using isolated cell populations from immune-competent and immune-deficient (knock-in and knock-out) donor mice we can analyse immune responses important for controlling M. perstans infection. Combining the two models opens up the potential to establish a laboratory cycle of M. perstans using an artificial membrane feeding system since we have elucidated the vector host (Culicoides milnei) in Cameroon. Collectively, this study should provide a future platform to study human filarial infections, eliminating the necessity of human volunteers as well as provide the basis for a long-term goal into the development of a rapid diagnostic test for M. perstans.

曼氏线虫Mansonella perstans（M. perstans）是撒哈拉以南非洲最流行的人类寄生虫之一，估计约有1.1亿人感染。与淋巴丝虫病或盘尾丝虫病不同，M. perstans感染没有引起明显的病理学，只有轻微的症状，如皮下积液、皮疹和胸膜炎。然而，有迹象表明，M。perstans影响其他感染的易感性和病程，这意味着在流行社区可能存在健康风险。对M. perstans一直受到无法获得蠕虫的阻碍，我们目前的研究已经通过开发两种新方法解决了这个问题：1）体外培养系统，以发展M。持久性蠕虫和2）使用RAG 2 IL-2 Rgamma缺陷型C57 BL/6实验室菌株扩大我们的丝虫小鼠模型。前者使M.持久丝虫。因此，我们将讨论M的未知方面。perstans生物学使用免疫染色和荧光显微镜破译蜕皮行为，分布和迁移的沃尔巴克氏体，解剖特征，也许是独特的这种丝虫。此外，我们最近的研究显示RAG 2 IL-2 R γ缺陷型C57 BL/6小鼠具有宿主对人类致病的丝虫的潜力。这种小鼠模型将提供一个新的平台，通过一系列的过继转移实验，使用来自免疫活性和免疫缺陷小鼠的分离细胞群，（敲入和敲除）供体小鼠，我们可以分析对于控制M.持久性感染。结合这两种模型，有可能建立一个实验室循环的M。perstans使用人工膜饲养系统，因为我们已经阐明了在喀麦隆的载体宿主（库蠓milnei）。总的来说，这项研究应该为研究人类丝虫感染提供一个未来的平台，消除人类志愿者的必要性，并为开发M的快速诊断测试的长期目标提供基础。perstans。