skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

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. Lastly, 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:
 [1];  [2];  [1];  [1];  [1];  [1];  [1];  [3];  [1];  [4]; ORCiD logo [5];  [1];  [3];  [1]
  1. Univ. de Lisboa, Lisboa (Portugal)
  2. Univ. de Lisboa, Lisboa (Portugal); Univ. of Texas Southwestern Medical Center, Dallas, TX (United States); Univ. do Porto, Porto (Portugal)
  3. Univ. of St. Andrews, Fife (United Kingdom)
  4. Institute of Tropical Medicine Antwerp, Antwerp (Belgium); Univ. of Ghent, Ghent (Belgium)
  5. Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Univ. de Lisboa, Lisboa (Portugal)
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
National Institutes of Health (NIH); USDOE
OSTI Identifier:
1341864
Report Number(s):
LA-UR-16-23520
Journal ID: ISSN 1931-3128
Grant/Contract Number:  
AC52-06NA25396
Resource Type:
Accepted Manuscript
Journal Name:
Cell Host & Microbe
Additional Journal Information:
Journal Volume: 19; Journal Issue: 6; Journal ID: ISSN 1931-3128
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; biological science; African trypanosomes; fat; mouse infection; fatty acid β-oxidation; metabolism; transcriptome

Citation Formats

Trindade, Sandra, Rijo-Ferreira, Filipa, Carvalho, Tania, Pinto-Neves, Daniel, Guegan, Fabien, Aresta-Branco, Francisco, Bento, Fabio, Young, Simon A., Pinto, Andreia, Van Den Abbeele, Jan, Ribeiro, Ruy M., Dias, Sergio, Smith, Terry K., and Figueiredo, Luisa M.. Trypanosoma brucei parasites occupy and functionally adapt to the adipose tissue in mice. United States: N. p., 2016. Web. https://doi.org/10.1016/j.chom.2016.05.002.
Trindade, Sandra, Rijo-Ferreira, Filipa, Carvalho, Tania, Pinto-Neves, Daniel, Guegan, Fabien, Aresta-Branco, Francisco, Bento, Fabio, Young, Simon A., Pinto, Andreia, Van Den Abbeele, Jan, Ribeiro, Ruy M., Dias, Sergio, Smith, Terry K., & Figueiredo, Luisa M.. Trypanosoma brucei parasites occupy and functionally adapt to the adipose tissue in mice. United States. https://doi.org/10.1016/j.chom.2016.05.002
Trindade, Sandra, Rijo-Ferreira, Filipa, Carvalho, Tania, Pinto-Neves, Daniel, Guegan, Fabien, Aresta-Branco, Francisco, Bento, Fabio, Young, Simon A., Pinto, Andreia, Van Den Abbeele, Jan, Ribeiro, Ruy M., Dias, Sergio, Smith, Terry K., and Figueiredo, Luisa M.. Thu . "Trypanosoma brucei parasites occupy and functionally adapt to the adipose tissue in mice". United States. https://doi.org/10.1016/j.chom.2016.05.002. https://www.osti.gov/servlets/purl/1341864.
@article{osti_1341864,
title = {Trypanosoma brucei parasites occupy and functionally adapt to the adipose tissue in mice},
author = {Trindade, Sandra and Rijo-Ferreira, Filipa and Carvalho, Tania and Pinto-Neves, Daniel and Guegan, Fabien and Aresta-Branco, Francisco and Bento, Fabio and Young, Simon A. and Pinto, Andreia and Van Den Abbeele, Jan and Ribeiro, Ruy M. and Dias, Sergio and Smith, Terry K. and Figueiredo, Luisa M.},
abstractNote = {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. Lastly, 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.},
doi = {10.1016/j.chom.2016.05.002},
journal = {Cell Host & Microbe},
number = 6,
volume = 19,
place = {United States},
year = {2016},
month = {5}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 27 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Trypanosoma brucei: Infection in murine diabetes
journal, December 1985


A transcription-independent epigenetic mechanism is associated with antigenic switching in Trypanosoma brucei
journal, December 2015

  • Aresta-Branco, Francisco; Pimenta, Silvia; Figueiredo, Luisa M.
  • Nucleic Acids Research, Vol. 44, Issue 7
  • DOI: 10.1093/nar/gkv1459

Species-Specific Adaptations of Trypanosome Morphology and Motility to the Mammalian Host
journal, February 2016


Comparative Proteomics of Two Life Cycle Stages of Stable Isotope-labeled Trypanosoma brucei Reveals Novel Components of the Parasite's Host Adaptation Machinery
journal, October 2012

  • Butter, Falk; Bucerius, Ferdinand; Michel, Margaux
  • Molecular & Cellular Proteomics, Vol. 12, Issue 1
  • DOI: 10.1074/mcp.M112.019224

HIV reservoirs as obstacles and opportunities for an HIV cure
journal, May 2015

  • Chun, Tae-Wook; Moir, Susan; Fauci, Anthony S.
  • Nature Immunology, Vol. 16, Issue 6
  • DOI: 10.1038/ni.3152

Bioluminescent Imaging of Trypanosoma brucei Shows Preferential Testis Dissemination Which May Hamper Drug Efficacy in Sleeping Sickness
journal, July 2009


Receptor-Mediated Endocytosis in the Bloodstream Form of Trypanosoma brucei 1
journal, November 1987


Target of Rapamycin (TOR)-like 1 Kinase Is Involved in the Control of Polyphosphate Levels and Acidocalcisome Maintenance in Trypanosoma brucei
journal, July 2010

  • de Jesus, Teresa Cristina Leandro; Tonelli, Renata Rosito; Nardelli, Sheila C.
  • Journal of Biological Chemistry, Vol. 285, Issue 31
  • DOI: 10.1074/jbc.M110.120212

Post-treatment hind-leg paralysis in mice infected with Trypanosoma brucei brucei: a light microscopic study
journal, February 1997


Evidence for Trypanosoma cruzi in adipose tissue in human chronic Chagas disease
journal, November 2011

  • Matos Ferreira, Adaliene Versiani; Segatto, Marcela; Menezes, Zélia
  • Microbes and Infection, Vol. 13, Issue 12-13
  • DOI: 10.1016/j.micinf.2011.06.002

From The Cover: Murine malaria parasite sequestration: CD36 is the major receptor, but cerebral pathology is unlinked to sequestration
journal, July 2005

  • Franke-Fayard, B.; Janse, C. J.; Cunha-Rodrigues, M.
  • Proceedings of the National Academy of Sciences, Vol. 102, Issue 32
  • DOI: 10.1073/pnas.0503386102

Murine Models for Trypanosoma brucei gambiense Disease Progression—From Silent to Chronic Infections and Early Brain Tropism
journal, September 2009

  • Giroud, Christiane; Ottones, Florence; Coustou, Virginie
  • PLoS Neglected Tropical Diseases, Vol. 3, Issue 9
  • DOI: 10.1371/journal.pntd.0000509

The Cytoskeleton of Trypanosomatid Parasites
journal, October 1999


Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness)
journal, February 2013


Computer Visualization of Three-Dimensional Image Data Using IMOD
journal, January 1996

  • Kremer, James R.; Mastronarde, David N.; McIntosh, J. Richard
  • Journal of Structural Biology, Vol. 116, Issue 1
  • DOI: 10.1006/jsbi.1996.0013

Transmission Stages Dominate Trypanosome Within-Host Dynamics during Chronic Infections
journal, April 2011


Trypanosomal immune evasion, chronicity and transmission: an elegant balancing act
journal, April 2012

  • MacGregor, Paula; Szöőr, Balazs; Savill, Nicholas J.
  • Nature Reviews Microbiology, Vol. 10, Issue 6
  • DOI: 10.1038/nrmicro2779

Highly Sensitive In Vivo Imaging of Trypanosoma brucei Expressing “Red-Shifted” Luciferase
journal, November 2013

  • McLatchie, Alex P.; Burrell-Saward, Hollie; Myburgh, Elmarie
  • PLoS Neglected Tropical Diseases, Vol. 7, Issue 11
  • DOI: 10.1371/journal.pntd.0002571

The in vivo dynamics of antigenic variation in Trypanosoma brucei
journal, March 2015


Is Adipose Tissue a Place for Mycobacterium tuberculosis Persistence?
journal, December 2006


Adipokines in inflammation and metabolic disease
journal, January 2011

  • Ouchi, Noriyuki; Parker, Jennifer L.; Lugus, Jesse J.
  • Nature Reviews Immunology, Vol. 11, Issue 2
  • DOI: 10.1038/nri2921

Functional Analysis of Leishmania Cyclopropane Fatty Acid Synthetase
journal, December 2012


T rypanosoma brucei histone H 1 inhibits RNA polymerase I transcription and is important for parasite fitness in vivo
journal, July 2014

  • Pena, Ana C.; Pimentel, Mafalda R.; Manso, Helena
  • Molecular Microbiology, Vol. 93, Issue 4
  • DOI: 10.1111/mmi.12677

Hyperlipidaemia in trypanosomiasis of naturally infected horses: possible cachexia–anorexia syndrome?
journal, July 2012

  • Ranjithkumar, Muthusamy; Malik, Tauseef Ahmed; Saxena, Anju
  • Tropical Animal Health and Production, Vol. 45, Issue 2
  • DOI: 10.1007/s11250-012-0232-z

Whole genome sequencing shows sleeping sickness relapse is due to parasite regrowth and not reinfection
journal, January 2016

  • Richardson, Joshua B.; Evans, Benjamin; Pyana, Patient P.
  • Evolutionary Applications, Vol. 9, Issue 2
  • DOI: 10.1111/eva.12338

Gene expression in Trypanosoma brucei: lessons from high-throughput RNA sequencing
journal, October 2011

  • Siegel, T. Nicolai; Gunasekera, Kapila; Cross, George A. M.
  • Trends in Parasitology, Vol. 27, Issue 10
  • DOI: 10.1016/j.pt.2011.05.006

Evolution, dynamics and specialized functions of glycosomes in metabolism and development of trypanosomatids
journal, December 2014

  • Szöör, Balázs; Haanstra, Jurgen R.; Gualdrón-López, Melisa
  • Current Opinion in Microbiology, Vol. 22
  • DOI: 10.1016/j.mib.2014.09.006

Influence of methods of preparation on the infectivity, agglutination, activity, and ultrastructure of bloodstream trypanosomes
journal, April 1974


Anisomorphic Cell Division by African Trypanosomes
journal, December 2001


Adaptations in the lipid metabolism of the protozoan parasite Trypanosoma brucei
journal, July 2006


Detailed interrogation of trypanosome cell biology via differential organelle staining and automated image analysis
journal, January 2012


The Limits on Trypanosomatid Morphological Diversity
journal, November 2013


    Works referencing / citing this record:

    Mitochondrial DNA is critical for longevity and metabolism of transmission stage Trypanosoma brucei
    journal, July 2018


    Gambian human African trypanosomiasis in North West Uganda. Are we on course for the 2020 target?
    journal, August 2019


    Molecular basis of fatty acid selectivity in the zDHHC family of S-acyltransferases revealed by click chemistry
    journal, February 2017

    • Greaves, Jennifer; Munro, Kevin R.; Davidson, Stuart C.
    • Proceedings of the National Academy of Sciences, Vol. 114, Issue 8
    • DOI: 10.1073/pnas.1612254114

    Effects of host‐derived chemokines on the motility and viability of Trypanosoma brucei
    journal, December 2018

    • Alfituri, Omar A.; Ajibola, Olumide; Brewer, James M.
    • Parasite Immunology, Vol. 41, Issue 2
    • DOI: 10.1111/pim.12609

    DNA lesions and repair in trypanosomatids infection
    journal, January 2020

    • Repolês, Bruno M.; Machado, Carlos Renato; Florentino, Pilar T. V.
    • Genetics and Molecular Biology, Vol. 43, Issue 1 suppl 1
    • DOI: 10.1590/1678-4685-gmb-2019-0163

    Using detergent-enhanced LAMP for African trypanosome detection in human cerebrospinal fluid and implications for disease staging
    journal, August 2019

    • Grab, Dennis J.; Nikolskaia, Olga V.; Courtioux, Bertrand
    • PLOS Neglected Tropical Diseases, Vol. 13, Issue 8
    • DOI: 10.1371/journal.pntd.0007631

    Microfluidics-Based Approaches to the Isolation of African Trypanosomes
    journal, October 2017


    Adipocyte Model of Mycobacterium tuberculosis Infection Reveals Differential Availability of Iron to Bacilli in the Lipid-Rich Caseous Environment
    journal, April 2018

    • Nandy, Ananya; Mondal, Anupam Kumar; Pandey, Rajesh
    • Infection and Immunity, Vol. 86, Issue 6
    • DOI: 10.1128/iai.00041-18

    Resolving the apparent transmission paradox of African sleeping sickness
    journal, January 2019


    Specific Biological Features of Adipose Tissue, and Their Impact on HIV Persistence
    journal, December 2019

    • Bourgeois, Christine; Gorwood, Jennifer; Barrail-Tran, Aurélie
    • Frontiers in Microbiology, Vol. 10
    • DOI: 10.3389/fmicb.2019.02837

    Disease Tolerance in Toxoplasma Infection
    journal, June 2019

    • Melchor, Stephanie J.; Ewald, Sarah E.
    • Frontiers in Cellular and Infection Microbiology, Vol. 9
    • DOI: 10.3389/fcimb.2019.00185

    Tissue tropism in parasitic diseases
    journal, May 2019

    • Silva Pereira, Sara; Trindade, Sandra; De Niz, Mariana
    • Open Biology, Vol. 9, Issue 5
    • DOI: 10.1098/rsob.190036

    Mutualist-Provisioned Resources Impact Vector Competency
    journal, June 2019


    African Trypanosomes Undermine Humoral Responses and Vaccine Development: Link with Inflammatory Responses?
    journal, May 2017


    Metabolic reprogramming during the Trypanosoma brucei life cycle
    journal, January 2017


    Host-parasite co-metabolic activation of antitrypanosomal aminomethyl-benzoxaboroles
    journal, February 2018


    Intravital imaging of host–parasite interactions in skin and adipose tissues
    journal, January 2019

    • De Niz, Mariana; Meehan, Gavin R.; Brancucci, Nicolas M. B.
    • Cellular Microbiology, Vol. 21, Issue 5
    • DOI: 10.1111/cmi.13023

    Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need
    journal, February 2017

    • Field, Mark C.; Horn, David; Fairlamb, Alan H.
    • Nature Reviews Microbiology, Vol. 15, Issue 4
    • DOI: 10.1038/nrmicro.2016.193

    Non-linear hierarchy of the quorum sensing signalling pathway in bloodstream form African trypanosomes
    journal, June 2018


    Neutrophils enhance early Trypanosoma brucei infection onset
    journal, July 2018


    RNAi screening identifies Trypanosoma brucei stress response protein kinases required for survival in the mouse
    journal, July 2017

    • Fernandez-Cortes, Fernando; Serafim, Tiago D.; Wilkes, Jonathan M.
    • Scientific Reports, Vol. 7, Issue 1
    • DOI: 10.1038/s41598-017-06501-8

    Faster growth with shorter antigens can explain a VSG hierarchy during African trypanosome infections: a feint attack by parasites
    journal, July 2018


    The Cytological Events and Molecular Control of Life Cycle Development of Trypanosoma brucei in the Mammalian Bloodstream
    journal, June 2017


    African trypanosomes
    journal, April 2019


    High-speed multifocal plane fluorescence microscopy for three-dimensional visualisation of beating flagella
    journal, August 2019

    • Walker, Benjamin J.; Wheeler, Richard J.
    • Journal of Cell Science, Vol. 132, Issue 16
    • DOI: 10.1242/jcs.231795

    The Trypanosoma cruzi RNA-binding protein RBP42 is expressed in the cytoplasm throughout the life cycle of the parasite
    journal, February 2018


    The skin is a significant but overlooked anatomical reservoir for vector-borne African trypanosomes
    journal, September 2016

    • Capewell, Paul; Cren-Travaillé, Christelle; Marchesi, Francesco
    • eLife, Vol. 5
    • DOI: 10.7554/elife.17716

    Escaping the immune system by DNA repair and recombination in African trypanosomes
    journal, November 2019

    • Sima, Núria; McLaughlin, Emilia Jane; Hutchinson, Sebastian
    • Open Biology, Vol. 9, Issue 11
    • DOI: 10.1098/rsob.190182

    Flagellar cAMP signaling controls trypanosome progression through host tissues
    journal, February 2019


    RNA-Seq analysis validates the use of culture-derived Trypanosoma brucei and provides new markers for mammalian and insect life-cycle stages
    journal, April 2018


    Mitochondrial dynamics in parasitic protists
    journal, November 2019


    Emerging challenges in understanding trypanosome antigenic variation
    journal, December 2017

    • McCulloch, Richard; Cobbold, Christina A.; Figueiredo, Luisa
    • Emerging Topics in Life Sciences, Vol. 1, Issue 6
    • DOI: 10.1042/etls20170104

    Gluconeogenesis using glycerol as a substrate in bloodstream-form Trypanosoma brucei
    journal, December 2018


    Safety and efficacy of three trypanocides in confirmed field cases of trypanosomiasis in working equines in The Gambia: a prospective, randomised, non-inferiority trial
    journal, March 2019


    Biological factors that impinge on Chagas disease drug development
    journal, August 2017

    • Francisco, Amanda F.; Jayawardhana, Shiromani; Lewis, Michael D.
    • Parasitology, Vol. 144, Issue 14
    • DOI: 10.1017/s0031182017001469

    The assembly of lipid droplets and their roles in challenged cells
    journal, March 2019


    Transcriptomes of Trypanosoma brucei rhodesiense from sleeping sickness patients, rodents and culture: Effects of strain, growth conditions and RNA preparation methods
    journal, February 2018


    Variation in disease phenotype is marked in equine trypanosomiasis
    journal, March 2020

    • Raftery, Alexandra G.; Jallow, Saloum; Coultous, Robert M.
    • Parasites & Vectors, Vol. 13, Issue 1
    • DOI: 10.1186/s13071-020-04020-6

    Parasite specific 7SL-derived small RNA is an effective target for diagnosis of active trypanosomiasis infection
    journal, February 2019

    • Chiweshe, Stephen M.; Steketee, Pieter C.; Jayaraman, Siddharth
    • PLOS Neglected Tropical Diseases, Vol. 13, Issue 2
    • DOI: 10.1371/journal.pntd.0007189

    A post-transcriptional respiratome regulon in trypanosomes
    journal, May 2019

    • Trenaman, Anna; Glover, Lucy; Hutchinson, Sebastian
    • Nucleic Acids Research, Vol. 47, Issue 13
    • DOI: 10.1093/nar/gkz455

    Developmental competence and antigen switch frequency can be uncoupled in Trypanosoma brucei
    journal, October 2019

    • McWilliam, Kirsty R.; Ivens, Alasdair; Morrison, Liam J.
    • Proceedings of the National Academy of Sciences, Vol. 116, Issue 45
    • DOI: 10.1073/pnas.1912711116

    Parasite motility is critical for virulence of African trypanosomes
    journal, June 2018


    Alternative oxidase inhibitors: Mitochondrion-targeting as a strategy for new drugs against pathogenic parasites and fungi
    journal, January 2019

    • Ebiloma, Godwin U.; Balogun, Emmanuel O.; Cueto-Díaz, Eduardo J.
    • Medicinal Research Reviews, Vol. 39, Issue 5
    • DOI: 10.1002/med.21560

    Sustainable Elimination (Zero Cases) of Sleeping Sickness: How Far Are We from Achieving This Goal?
    journal, August 2019


    Sleeping sickness is a circadian disorder
    journal, January 2018

    • Rijo-Ferreira, Filipa; Carvalho, Tânia; Afonso, Cristina
    • Nature Communications, Vol. 9, Issue 1
    • DOI: 10.1038/s41467-017-02484-2

    Trypanosoma brucei triggers a marked immune response in male reproductive organs
    journal, August 2018


    Application of long read sequencing to determine expressed antigen diversity in Trypanosoma brucei infections
    journal, April 2019


    Trypanosoma brucei infection protects mice against malaria
    journal, November 2019


    A quorum sensing-independent path to stumpy development in Trypanosoma brucei
    journal, April 2017


    Identification of Positive Chemotaxis in the Protozoan Pathogen Trypanosoma brucei
    journal, August 2020


    Metabolic reprogramming during the Trypanosoma brucei life cycle
    journal, January 2017


    The assembly of lipid droplets and their roles in challenged cells
    journal, May 2018

    • Henne, W. Mike; Reese, Michael L.; Goodman, Joel M.
    • The EMBO Journal, Vol. 37, Issue 12
    • DOI: 10.15252/embj.201898947

    Mitochondrial DNA is critical for longevity and metabolism of transmission stage Trypanosoma brucei.
    text, January 2018

    • Dewar, Caroline E.; MacGregor, Paula; Cooper, Sinclair
    • Apollo - University of Cambridge Repository
    • DOI: 10.17863/cam.32944

    Flagellar cAMP signaling controls trypanosome progression through host tissues.
    text, January 2019

    • Shaw, Sebastian; DeMarco, Stephanie F.; Rehmann, Ruth
    • Nature Publishing Group
    • DOI: 10.7892/boris.130288