Exploring and targeting the kinome of immune cells exposed to African trypanosomes.

Neutrophils and macrophages are cells of the innate immune system of the mammalian host with a range of potential effector functions against pathogens. These cells are rapidly recruited to sites of parasite infection. Counterintuitively, neutrophils favor the onset of parasite infections as we have described for sleeping sickness parasites (Trypanosoma brucei sp.) inoculated by the bites of tsetse flies. Indeed, selective neutrophil removal or genetic conditions resulting in lower neutrophil levels in the blood yield a higher level of resistance to trypanosome infection. Monocytes on the other hand are activated to differentiate into activated macrophages that contribute to parasite control in the early stage of infection. The differential impact of neutrophils and macrophages suggests that specific inhibition of neutrophil functions could result in higher levels of resistance to infection. This project will compare the responses of neutrophils and monocytes to parasite presence by capturing their kinase activity fingerprints. Kinase targets in cell type specific and common responsive pathways will be identified. Kinase inhibitors from commercially available or proprietary collections will be used to selectively inhibit the parasite-induced responses and to evaluate the impact on parasite infection. Collectively, this project will forward our understanding of early trypanosome transmission and is directed at revealing novel transmission-blocking concepts and strategies.

Keywords:TRYPANOSOMIASIS

Disciplines:Microbiology, Veterinary medicine