Molecular adaptation of the tsetse fly transmited African trypanosome to the intradermal micro-environment in the mammalian host

Human african trypanosomiasis (HAT), also known as sleeping sickness, is caused by the rhodesiense and gambiense subspecies of Trypanosoma brucei. HAT has a severe social and economic impact and, although the number of reported new cases are low and decreasing, it is still a major threat for 70 million people living in 1.55 M km2 of sub-Saharan Africa. Currently, despite of intensive research, an effective vaccine that can protect humans and/or animals from infection is not available nor under development and existing drug formulations suffer significant levels of toxicity as wel as the acquisition of parasite resistance towards the available drugs. Trypanosoma brucei is a vector-borne pathogen whereby the parasite alternates its life cycle between a mammalian host and the blood feeding tsetse fly (Glossina spp). Through the bite of an infected tsetse fly, metacyclic trypanosomes are inoculated in the host skin. Here, trypanosomes will adapt and establish and eventually migrate to the peripheral blood of the mammalian host which results in a systemic infection. Although this transmission is a crucial event in the parasite life cycle, so far only very few studies have addressed the early parasitological features of a naturally transmitted trypanosome infection in the mammalian host. As a result, the current knowledge on the early interface between the tsetse transmitted trypanosomes and the mammalian host skin is highly limited and not sufficiently exploited as a potential target for pathogen transmission control. Our hypothesis is that during the early intradermal stage, tsetse-inoculated metacyclic trypanosomes differentiate into a specific parasite stage in the host skin that is adapted to this micro-environment. With focused experimental work using an in vivo tsetse fly-trypanosome-animal model we want to identify the trypanosome and/or host components that play an essential role in the survival, adaptation and/or parasite escape from the host innate immune response during this crucial life cycle stage. Potentially, these crucial components could be suitable targets for e.g. vaccine development to block this early transmission and subsequent systemic infection of the host.

Trefwoorden:B780-tropische-geneeskunde