Trypanosoma brucei Parasites Occupy and Functionally Adapt to the Adipose Tissue in Mice.

Fabio Bento,Sandra Trindade,Ruy M. Ribeiro,Sérgio Dias,Simon A. Young,Fabien Guegan,Luisa M. Figueiredo,Francisco Aresta-Branco,Andreia Pinto,Tânia Carvalho,Terry K. Smith,Jan Van Den Abbeele,Filipa Rijo-Ferreira,Daniel Pinto-Neves

doi:10.1016/j.chom.2016.05.002

Abstract

SummaryTrypanosoma brucei is an extracellular parasite that causes sleeping sickness. In mammalian hosts, trypanosomes are thought to exist in two major niches: early in infection, they populate the blood; later, they breach the blood-brain barrier. Working with a well-established mouse model, we discovered that adipose tissue constitutes a third major reservoir for T. brucei. Parasites from adipose tissue, here termed adipose tissue forms (ATFs), can replicate and were capable of infecting a naive animal. ATFs were transcriptionally distinct from bloodstream forms, and the genes upregulated included putative fatty acid β-oxidation enzymes. Consistent with this, ATFs were able to utilize exogenous myristate and form β-oxidation intermediates, suggesting that ATF parasites can use fatty acids as an external carbon source. These findings identify the adipose tissue as a niche for T. brucei during its mammalian life cycle and could potentially explain the weight loss associated with sleeping sickness.

Highlights

Human African trypanosomiasis (HAT), known as sleeping sickness, is a neglected tropical disease that is almost always fatal if left untreated. This disease is caused by Trypanosoma brucei, a unicellular parasite that lives in the blood, lymphatic system, and interstitial spaces of organs
Slender forms are capable of sensing population density, and this triggers differentiation to the stumpy form, which is pre-adapted to life in the transmitting tsetse vector and, once there, further differentiates into procyclic form (PCF)
Several studies have shown 10%–30% of genes being differentially expressed between bloodstream form (BSF) and PCFs, including genes involved in metabolism, organelle activity, cell-cycle regulation, and endocytic activity

Summary

Introduction

Human African trypanosomiasis (HAT), known as sleeping sickness, is a neglected tropical disease that is almost always fatal if left untreated This disease is caused by Trypanosoma brucei, a unicellular parasite that lives in the blood, lymphatic system, and interstitial spaces of organs (reviewed in Kennedy, 2013). Disease pathology often correlates with sites of accumulation of the infectious agent within its host, including the brain, which is associated with characteristic neuropsychiatric symptoms and sleep disorder. Weight loss is another typical clinical feature of sleeping sickness pathology (Kennedy, 2013), but is essentially unstudied. Recent proteomic studies revealed around 33% of proteins that are developmentally regulated (Butter et al, 2013)

Results

Discussion

Conclusion