Innate immune response in the mammalian host skin after the bite of a trypanosome-infected tsetse fly (INNATEBITE)

To establish a systemic infection, vector-borne pathogens must overcome initial immune detection in the skin. This detection is by a limited but powerful repertoire of germline-encoded pathogen recognitions receptors (PRRs) that detect microbial molecular patterns and tissue damage and are broadly expressed by immune and non-immune cells. African trypanosomes are transmitted to the mammalian host skin by bite of the tsetse fly. The parasite’s high proficiency in overcoming the intradermal hurdle suggests that it has evolved highly effective mechanisms for escaping and/or modulating innate immune responses . However, which PRRs in which immune cell populations are activated by the parasite in the skin and how these responses could be suppressed or modulated by the parasite and/or tsetse saliva remain to be elucidated. In this project, we aim to profile the immune landscape and its transcriptional plasticity at the infected tsetse bite site and to assess the immune-modulatory activity of parasite and tsetse saliva on skin-resident and bite-site recruited immune cells. We will then determine in vivo the impact of the innate immune environment at the bite site on the developmental progress of the tsetse-injected trypanosomes. Advancing our basic knowledge of this key tsetse-to-host transition step can potentially inform novel prophylactic and therapeutic approaches for interfering with the parasite development at this vulnerable entry point in its vertebrate host.

Project type:Collaboration project