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

• Applicant: Dr. Manuel Ritter
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 405531500

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.

• DFG Programme: Research Grants
• International Connection: Cameroon
• Co-Investigator: Dr. Laura Elizabeth Layland-Heni
• International Co-Applicant: Professor Dr. Samuel Wanji