title: Trypanosoma brucei Parasites Occupy and Functionally Adapt to the Adipose Tissue in Mice.
abstract: 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.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1990-375 Lisboa, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Trindade
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1990-375 Lisboa, Portugal; Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA; Graduate Program in Areas of Basic and Applied Biology, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4099-002 Porto, Portugal.
authors.forename: Filipa
authors.initials: F
authors.lastname: Rijo-Ferreira
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1990-375 Lisboa, Portugal.
authors.forename: Tânia
authors.initials: T
authors.lastname: Carvalho
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1990-375 Lisboa, Portugal.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pinto-Neves
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1990-375 Lisboa, Portugal.
authors.forename: Fabien
authors.initials: F
authors.lastname: Guegan
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1990-375 Lisboa, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Aresta-Branco
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1990-375 Lisboa, Portugal.
authors.forename: Fabio
authors.initials: F
authors.lastname: Bento
authors.affiliation: Biomedical Sciences Research Complex, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Young
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1990-375 Lisboa, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Pinto
authors.affiliation: Department of Biomedical Sciences, Unit of Veterinary Protozoology, Institute of Tropical Medicine Antwerp, B-2000 Antwerp, Belgium; Department of Physiology, Laboratory of Zoophysiology, University of Ghent, B-9000 Ghent, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Van Den Abbeele
authors.affiliation: Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA; Guest Professor, Faculdade de Medicina, Universidade de Lisboa, 1990-375 Lisboa, Portugal.
authors.forename: Ruy M
authors.initials: RM
authors.lastname: Ribeiro
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1990-375 Lisboa, Portugal.
authors.forename: Sérgio
authors.initials: S
authors.lastname: Dias
authors.affiliation: Biomedical Sciences Research Complex, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK.
authors.forename: Terry K
authors.initials: TK
authors.lastname: Smith
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1990-375 Lisboa, Portugal. Electronic address: lmf@medicina.ulisboa.pt.
authors.forename: Luisa M
authors.initials: LM
authors.lastname: Figueiredo
mesh_terms: D000273:Adipose Tissue / Q000469:parasitology* / Q000473:pathology; D000818:Animals; D001483:Base Sequence; D004195:Disease Models, Animal; D008018:Life Cycle Stages; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019814:Myristic Acid / Q000378:metabolism; D010084:Oxidation-Reduction; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D014353:Trypanosomiasis, African / Q000097:blood / Q000469:parasitology* / Q000473:pathology
chemical_list: D015800:Protozoan Proteins; D019814:Myristic Acid
keywords: African trypanosomes; fat; fatty acid β-oxidation; metabolism; mouse infection; transcriptome