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

Trypanosoma 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. [Display omitted] •T. brucei parasites accumulate in the adipose tissue early after mouse infection•Adipose tissue forms (ATFs) can replicate and are capable of infecting naive mice•ATFs are transcriptionally distinct and upregulate genes for fatty acid metabolism•ATFs can actively uptake exogenous myristate and form β-oxidation intermediates Trypanosoma brucei is found in the bloodstream and interstitial compartment of several organs in the mammalian host. Trindade et al. uncover the adipose tissue as a major extravascular parasite niche. Extensive remodeling of parasite gene expression in this lipid-rich environment includes upregulation of fatty acid β-oxidation enzymes, suggestive of a functional adaptation.