Authors

Discussion

Trypanosoma brucei is an extracellular protozoan parasite that causes Human African Sleeping Sickness (HAT). Trypanosomes are thought to be found in two major niches during mammalian host infection; in the blood and lymphatic system during the early stage infection, and later in the central nervous system (CNS). This later stage is characterised by neuropsychiatric symptoms and sleep disorders that occur through an undefined mechanism. Trypanosomes cultured in vitro significantly deplete tryptophan from the media, using it in both protein synthesis and transamination reactions.¹ As well as forming an essential component of the kynurenine pathway, with both neurotoxic and neuroprotective branches, tryptophan is also the precursor serotonin and melatonin which are implicated in sleep regulation. ²

Parasite localisation to other tissues types has often been overlooked; however Trindade and colleagues ³ recently documented the presence of trypanosomes in extravascular adipose tissue, and Capewell and colleagues demonstrated the skin to be a significant anatomical reservoir. ⁴

Working with a well-established murine model of infection using red-shifted luciferase expressing parasites (REF⁵), our ex vivo imaging data reveals parasite sequestration to many organs during early stage infection not previously documented. In addition, we identified localisation to the CNS during the early stage infection in a subset of animals. HPLC-based metabolomics analysis has been used to determine tryptophan uptake and metabolism during the course of infection.

This preliminary data raises some interesting points regarding tropism, or lack of it, during Trypanosoma brucei infection in the mammalian host. Our current work aims to relate parasite localisation to specific areas within the brain, with altered brain function, metabolism and translationally relevant behavioural changes in the mouse model. This is a clinically relevant area of research which remains to be well defined.

1. Stibbs H.H., & Seed J.R., (1975) Short-term metabolism of [14C] tryptophan in rats infected with Trypanosoma brucei gambiense. Journal of Infectious Diseases. 131(4): 459-462 2.

2. Rodgers J., et al. (2009). Kynurenine pathway inhibition reduces central nervous system inflammation in a model of human African trypanosomiasis. Brain. 132(5): 1259-1267 3.

3. Trindade S., et al. (2016). Trypanosoma brucei parasites occupy and functionally adapt to the adipose tissue in mice. Cell host & microbe 19(6):837-848 4.

4. Capewell P., et al. (2016). The skin is a significant but overlooked anatomical reservoir for vector-borne African trypanosomes. Elife 5: e17716 5.

5. McLatchie AP., et al. (2013). Highly sensitive in vivo imaging of Trypanosoma brucei expressing “red-shifted” luciferase. PLoS neglected tropical diseases 7(11): e2571