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Escape mechanisms of African trypanosomes: why trypanosomosis is keeping us awake

Published online by Cambridge University Press:  05 December 2014

JENNIFER CNOPS ,
STEFAN MAGEZ  and
CARL De TREZ
JENNIFER CNOPS*
Affiliation:
Laboratory for Cellular and Molecular Immunology, Vrije Universiteit Brussel, Building E8.01, Pleinlaan 2, 1050 Brussels, Belgium Department of Structural Biology, VIB, Brussels, Belgium
STEFAN MAGEZ
Affiliation:
Laboratory for Cellular and Molecular Immunology, Vrije Universiteit Brussel, Building E8.01, Pleinlaan 2, 1050 Brussels, Belgium Department of Structural Biology, VIB, Brussels, Belgium
CARL De TREZ
Affiliation:
Laboratory for Cellular and Molecular Immunology, Vrije Universiteit Brussel, Building E8.01, Pleinlaan 2, 1050 Brussels, Belgium Department of Structural Biology, VIB, Brussels, Belgium
*
*Corresponding author. Vrije Universiteit Brussel (VUB), Building E8.01, Pleinlaan 2, 1050 Brussels, Belgium. E-mail: jcnops@vub.ac.be
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Summary

African trypanosomes have been around for more than 100 million years, and have adapted to survival in a very wide host range. While various indigenous African mammalian host species display a tolerant phenotype towards this parasitic infection, and hence serve as perpetual reservoirs, many commercially important livestock species are highly disease susceptible. When considering humans, they too display a highly sensitive disease progression phenotype for infections with Trypanosoma brucei rhodesiense or Trypanosoma brucei gambiense, while being intrinsically resistant to infections with other trypanosome species. As extracellular trypanosomes proliferate and live freely in the bloodstream and lymphatics, they are constantly exposed to the immune system. Due to co-evolution, this environment however no longer poses a hostile threat, but has become the niche environment where trypanosomes thrive and obligatory await transmission through the bites of tsetse flies or other haematophagic vectors, ideally without causing severe side infection-associated pathology to their host. Hence, African trypanosomes have acquired various mechanisms to manipulate and control the host immune response, evading effective elimination. Despite the extensive research into trypanosomosis over the past 40 years, many aspects of the anti-parasite immune response remain to be solved and no vaccine is currently available. Here we review the recent work on the different escape mechanisms employed by African Trypanosomes to ensure infection chronicity and transmission potential.

Keywords

African trypanosomesescape mechanismsimmune modulationinflammationantigenic variation
Type
Review Article
Information
Parasitology , Volume 142 , Issue 3 , March 2015 , pp. 417 - 427
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Copyright © Cambridge University Press 2014 

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References

REFERENCES

Alexandre, S., Paindavoine, P., Tebabi, P., Halleux, S., Steinert, M. and Pays, E. (1990). Differential expression of a family of putative adenylate/guanylate cyclase genes in Trypanosoma brucei. Molecular and Biochemical Parasitology 43, 279–288.CrossRefGoogle ScholarPubMed
Alexandre, S., Paindavoine, P., Hanocq-Quertier, J., Paturiaux-hanocq, F., Tebabi, P. and Pays, E. (1996). Families of adenylate cyclase genes in Trypanosoma brucei’. Molecular and Biochemical Parasitology 77, 173–182.CrossRefGoogle ScholarPubMed
Alsford, S., Currier, R. B., Guerra-Assunção, J. A., Clark, T. G. and Horn, D. (2014). Cathepsin-L can resist lysis by human serum in Trypanosoma brucei brucei . PLoS Pathogens 10, e1004130.Google Scholar
Authie, E., Biulange, A., Muteti, D., Lalmanach, G., Gauthier, F. and Musoke, A. (2001). Immunisation of cattle with cysteine proteinases of Trypanosoma congolense: targeting the disease rather than the parasite. International Journal for Parasitology 31, 1429–1433.CrossRefGoogle ScholarPubMed
Baltz, T., Baltz, D., Giroud, C. and Pautrizel, R. (1981). Immune depression and macroglobulinemia in experimental subchronic trypanosomiasis. Infection and Immunity 32(3), 979–984.CrossRefGoogle ScholarPubMed
Baral, T. N. (2010). Immunobiology of African trypanosomes: need of alternative interventions. Journal of Biomedicine & Biotechnology 2010, 389153.Google Scholar
Barry, J. D. (1979). Capping of variable antigen on Trypanosoma brucei, and its immunological and biological significance. Journal of Cell Science 37, 287–302.Google Scholar
Berriman, M., Hall, N., Sheader, K., Bringaud, F., Tiwari, B., Isobe, T., Bowman, S., Corton, C., Clark, L., Cross, G. A. M., Hoek, M., Zanders, T., Berberof, M., Borst, P. and Rudenko, G. (2002). The architecture of variant surface glycoprotein gene expression sites in Trypanosoma brucei . Molecular and Biochemical Parasitology 122, 131–140.CrossRefGoogle ScholarPubMed
Beschin, A., Van Den Abbeele, J., De Baetselier, P. and Pays, E. (2014). African trypanosome control in the insect vector and mammalian host. Trends in Parasitology 4922, 4922.Google Scholar
Blum, J., Nkunku, S. and Burri, C. (2001). Clinical description of encephalopathic syndromes and risk factors for their occurrence and outcome during melarsoprol treatment of human African trypanosomiasis. Tropical Medicine International Health 6(5), 390–400.CrossRefGoogle ScholarPubMed
Blum, J., Schmid, C. and Burri, C. (2006). Clinical aspects of 2541 patients with second stage human African trypanosomiasis. Acta Tropica 97, 55–64.Google Scholar
Bockstal, V., Geurts, N. and Magez, S. (2011 a). Acute disruption of bone Marrow B Lymphopoiesis and Apoptosis of transitional and Marginal Zone B cells in the spleen following a blood-stage plasmodium chabaudi infection in mice. Journal of Parasitology Research 2011, 534697.Google Scholar
Bockstal, V., Guirnalda, P., Caljon, G., Goenka, R., Telfer, J. C., Frenkel, D., Radwanska, M., Magez, S. and Black, S. J. (2011 b). T. brucei infection reduces B lymphopoiesis in bone marrow and truncates compensatory splenic lymphopoiesis through transitional B-cell apoptosis. PLoS Pathogens 7, e1002089.CrossRefGoogle ScholarPubMed
Borst, P. (2002). Antigenic variation and allelic exclusion. Cell 109, 5–8.Google Scholar
Campbell, G. H., Esser, K. M. and Weinbaum, F. I. (1977). Trypanosoma rhodesiense infection in B-cell-deficient mice. Infection and Immunity 18, 434–438.Google Scholar
Capewell, P., Veitch, N. J., Turner, C. M. R., Raper, J., Berriman, M., Hajduk, S. L. and MacLeod, A. (2011). Differences between Trypanosoma brucei gambiense groups 1 and 2 in their resistance to killing by trypanolytic factor 1. PLoS Neglected Tropical Diseases 5, e1287.Google Scholar
Capewell, P., Clucas, C., DeJesus, E., Kieft, R., Hajduk, S., Veitch, N., Steketee, P. C., Cooper, A., Weir, W. and MacLeod, A. (2013). The TgsGP gene is essential for resistance to human serum in Trypanosoma brucei gambiense . PLoS Pathogens 9, e1003686.Google Scholar
Corsini, A. C., Clayton, C., Askonas, B. A. and Ogilvie, B. M. (1977). Suppressor cells and loss of B-cell potential in mice infected with Trypanosoma brucei . Clinical and Experimental Immunology 29, 122–131.Google ScholarPubMed
Da Silva, A. S., Garcia Perez, H. A., Costa, M. M., França, R. T., De Gasperi, D., Zanette, R. A., Amado, J. A., Lopes, S. T. A., Teixeira, M. M. G. and Monteiro, S. G. (2011). Horses naturally infected by Trypanosoma vivax in southern Brazil. Parasitology Research 108, 23–30.Google Scholar
Dagenais, T. R., Freeman, B. E., Demick, K. P., Paulnock, D. M. and Mansfield, J. M. (2009). Processing and presentation of variant surface glycoprotein molecules to T cells in African trypanosomiasis. Journal of Immunology (Baltimore, Md.: 1950) 183, 3344–3355.Google Scholar
De Gee, A., Mccann, P. P. and Mansfield, J. M. (1983). Role of antibody in the elimination of trypanosomes after DL-alpha-difluoromethylornithine chemotherapy. The Journal of Parasitology 69, 818–822.Google Scholar
De Greef, C., Imberechts, H., Matthyssens, G., Van Meirvenne, N. and Hamers, R. (1989). A gene expressed only in serum-resistant variants of Trypanosoma brucei rhodesiense. Molecular and Biochemical Parasitology 36, 169–176.CrossRefGoogle ScholarPubMed
DeJesus, E., Kieft, R., Albright, B., Stephens, N. A. and Hajduk, S. L. (2013). A single amino acid substitution in the group 1 Trypanosoma brucei gambiense haptoglobin–hemoglobin receptor abolishes TLF-1 binding. PLoS Pathogens 9, e1003317.Google Scholar
Desquesnes, M., Dargantes, A., Lai, D.-H., Lun, Z.-R., Holzmuller, P. and Jittapalapong, S. (2013). Trypanosoma evansi and surra: a review and perspectives on transmission, epidemiology and control, impact, and zoonotic aspects. BioMed Research International 2013, 321237.Google Scholar
Diffley, P. (1983). Trypanosomal surface coat variant antigen causes polyclonal lymphocyte activation. Journal of Immunology 131, 1983–1986.Google Scholar
Drain, J., Bishop, J. R. and Hajduk, S. L. (2001). Haptoglobin-related protein mediates trypanosome lytic factor binding to trypanosomes. Journal of Biological Chemistry 276, 30254–30260.Google Scholar
Drennan, M. B., Stijlemans, B., Van Den, J., Quesniaux, V. J., Barkhuizen, M., De Baetselier, P., Ryffel, B. and Magez, S. (2005). The induction of a Type 1 immune response following a Trypanosoma brucei infection is MyD88 dependent. The Journal of Immunology 175, 2501–2509.Google Scholar
Engstler, M., Pfohl, T., Herminghaus, S., Boshart, M., Wiegertjes, G., Heddergott, N. and Overath, P. (2007). Hydrodynamic flow-mediated protein sorting on the cell surface of trypanosomes. Cell 131, 505–515.Google Scholar
Enyaru, J. C. K., Matovu, E., Nerima, B., Akol, M. and Sebikali, C. (2006). Detection of T.b. rhodesiense trypanosomes in humans and domestic animals in south east Uganda by amplification of serum resistance-associated gene. Annals of the New York Academy of Sciences 1081, 311–319.CrossRefGoogle Scholar
Field, M. C. and Carrington, M. (2009). The trypanosome flagellar pocket. Nature reviews in microbiology 7, 775–786.Google Scholar
Figueiredo, L. M., Janzen, C. J. and Cross, G. A M. (2008). A histone methyltransferase modulates antigenic variation in African trypanosomes. PLoS Biology 6, e161.Google Scholar
Gibson, W., Nemetschke, L. and Ndung'u, J. (2010). Conserved sequence of the TgsGP gene in Group 1 Trypanosoma brucei gambiense. Infection, Genetics and Evolution 10, 453–458.Google Scholar
Goodwin, L. G., Green, D. G., Guy, M. W. and Voller, A. (1972). Immunosuppression during trypanosomiasis. British Journal of Experimental Pathology 53, 40–43.Google Scholar
Green, H. P., Del Pilar Molina Portela, M., St Jean, E. N., Lugli, E. B. and Raper, J. (2003). Evidence for a Trypanosoma brucei lipoprotein scavenger receptor. Journal of Biological Chemistry 278, 422–427.Google Scholar
Guirnalda, P., Murphy, N. B., Nolan, D. and Black, S. J. (2007). Anti-Trypanosoma brucei activity in Cape buffalo serum during the cryptic phase of parasitemia is mediated by antibodies. International Journal for Parasitology 37, 1391–1399.Google Scholar
Hager, K. M., Pierce, M. A, Moore, D. R., Tytler, E. M., Esko, J. D. and Hajduk, S. L. (1994). Endocytosis of a cytotoxic human high density lipoprotein results in disruption of acidic intracellular vesicles and subsequent killing of African trypanosomes. Journal of Cell Biology 126, 155–167.Google Scholar
Hall, J. P. J., Wang, H. and Barry, J. D. (2013). Mosaic VSGs and the scale of Trypanosoma brucei antigenic variation. PLoS Pathogens 9, e1003502.CrossRefGoogle ScholarPubMed
Hertz, C. J., Filutowicz, H. and Mansfield, J. M. (1998). Resistance to the African trypanosomes is IFN-gamma dependent. Journal of Immunology (Baltimore, Md.: 1950) 161, 6775–6783.Google Scholar
Higgins, M. K., Tkachenko, O., Brown, A., Reed, J., Raper, J. and Carrington, M. (2013). Structure of the trypanosome haptoglobin–hemoglobin receptor and implications for nutrient uptake and innate immunity. Proceedings of the National Academy of Sciences 110, 1905–1910.CrossRefGoogle ScholarPubMed
Horn, D. and McCulloch, R. (2010). Molecular mechanisms underlying the control of antigenic variation in African trypanosomes. Current Opinion in Microbiology 13, 700–705.Google Scholar
Hughes, K., Wand, M., Foulston, L., Young, R., Harley, K., Terry, S., Ersfeld, K. and Rudenko, G. (2007). A novel ISWI is involved in VSG expression site downregulation in African trypanosomes. The EMBO journal 26, 2400–2410.Google Scholar
Jackson, A. P., Sanders, M., Berry, A., McQuillan, J., Aslett, M. A., Quail, M. A., Chukualim, B., Capewell, P., MacLeod, A., Melville, S. E., Gibson, W., Barry, J. D., Berriman, M. and Hertz-Fowler, C. (2010). The genome sequence of Trypanosoma brucei gambiense, causative agent of chronic human african trypanosomiasis. PLoS Negl Trop Dis 4, e658.Google Scholar
Kooter, J. M., van der Spek, H. J., Wagter, R., d'Oliveira, C. E., van der Hoeven, F., Johnson, P. J. and Borst, P. (1987). The anatomy and transcription of a telomeric expression site for variant-specific surface antigens in T. brucei . Cell 51, 261–272.CrossRefGoogle ScholarPubMed
La Greca, F. and Magez, S. (2011). Vaccination against trypanosomiasis: can it be done or is the trypanosome truly the ultimate immune destroyer and escape artist? Human Vaccines 7, 1225–1233.CrossRefGoogle ScholarPubMed
La Greca, F., Haynes, C., Stijlemans, B., De Trez, C. and Magez, S. (2014). Antibody-mediated control of Trypanosoma vivax infection fails in the absence of tumour necrosis factor. Parasite Immunology 36, 271–276.Google Scholar
Lacomble, S., Vaughan, S., Gadelha, C., Morphew, M. K., Shaw, M. K., McIntosh, J. R. and Gull, K. (2010). Basal body movements orchestrate membrane organelle division and cell morphogenesis in Trypanosoma brucei . Journal of Cell Science 123, 2884–2891.Google Scholar
Lança, S., Pires de Sousa, K., Atouguia, J., Prazeres, M. D., Monteiro, G. A. and Sousa Silva, M. (2011). Trypanosoma brucei: immunisation with plasmid DNA encoding invariant surface glycoprotein gene is able to induce partial protection in experimental African trypanosomiasis. Experimental Parasitology 127, 18–24.Google Scholar
Landeira, D., Bart, J.-M., Van Tyne, D. and Navarro, M. (2009). Cohesin regulates VSG monoallelic expression in trypanosomes. Journal of Cell Biology 186, 243–254.Google Scholar
Langousis, G. and Hill, K. L. (2014). Motility and more: the flagellum of Trypanosoma brucei . Nature Reviews. Microbiology 12, 505–518.Google Scholar
Lecordier, L., Uzureau, P., Tebabi, P., Pérez-Morga, D., Nolan, D., Schumann Burkard, G., Roditi, I. and Pays, E. (2014). Identification of Trypanosoma brucei components involved in trypanolysis by normal human serum. Molecular Microbiology Epub ahead, 12783.Google Scholar
Lejon, V., Mumba Ngoyi, D., Kestens, L., Boel, L., Barbé, B., Kande Betu, V., van Griensven, J., Bottieau, E., Muyembe Tamfum, J.-J., Jacobs, J. and Büscher, P. (2014). Gambiense human african trypanosomiasis and immunological memory: effect on phenotypic lymphocyte profiles and humoral immunity. PLoS Pathogens 10, e1003947.Google Scholar
Li, S.-Q., Yang, W.-B., Lun, Z.-R., Ma, L.-J., Xi, S.-M., Chen, Q.-L., Song, X.-W., Kang, J. and Yang, L.-Z. (2009). Immunization with recombinant actin from Trypanosoma evansi induces protective immunity against T. evansi, T. equiperdum and T. b. brucei infection. Parasitology Research 104, 429–435.Google Scholar
Lugli, E. B., Pouliot, M., Portela, M. D. P. M., Loomis, M. R. and Raper, J. (2004). Characterization of primate trypanosome lytic factors. Molecular and Biochemical Parasitology 138, 9–20.CrossRefGoogle ScholarPubMed
MacLean, L. M., Odiit, M., Chisi, J. E., Kennedy, P. G. E. and Sternberg, J. M. (2010). Focus-specific clinical profiles in human African Trypanosomiasis caused by Trypanosoma brucei rhodesiense. PLoS Neglected Tropical Diseases 4, e906.Google Scholar
Magez, S., Radwanska, M., Beschin, A., Sekikawa, K. and De Baetselier, P. (1999). Tumor necrosis factor alpha is a key mediator in the regulation of experimental Trypanosoma brucei infections. Infection and Immunity 67, 3128–3132.Google Scholar
Magez, S., Schwegmann, A., Atkinson, R., Claes, F., Drennan, M., De Baetselier, P. and Brombacher, F. (2008). The role of B-cells and IgM antibodies in parasitemia, anemia, and VSG switching in Trypanosoma brucei-infected mice. PLoS Pathogens 4, e1000122.Google Scholar
Mansfield, J. M. and Paulnock, D. M. (2005). Regulation of innate and acquired immunity in African trypanosomiasis. Parasite Immunology 27, 361–371.Google Scholar
Mansfield, J. M. and Wallace, J. H. (1974). Suppression of cell-mediated immunity in experimental African trypanosomiasis. Infection 10, 335–339.Google ScholarPubMed
Matthews, K. R., Ellis, J. R. and Paterou, A. (2004). Molecular regulation of the life cycle of African trypanosomes. Trends in Parasitology 20, 40–47.CrossRefGoogle ScholarPubMed
McLintock, L. M. L., Turner, C. M. R. and Vickerman, K. (1993). Comparison of the effects of immune killing mechanisms on Trypanosoma brucei parasites of slender and stumpy morphology. Parasite Immunology 15, 475–480.Google Scholar
Mkunza, F., Aloho, W. and Powell, C. (1995). Partial protection against natural trypanosomiasis after vaccination with a flagellar pocket antigen from. Vaccine 13, 151–154.Google Scholar
Mony, B. M., Macgregor, P., Ivens, A., Rojas, F., Cowton, A., Young, J., Horn, D. and Matthews, K. (2014). Genome wide dissection of the quorum sensing signaling pathway in Trypanosoma brucei . Nature 505, 681–685.Google Scholar
Morrison, L. J., Marcello, L. and McCulloch, R. (2009). Antigenic variation in the African trypanosome: molecular mechanisms and phenotypic complexity. Cellular Microbiology 11, 1724–1734.Google Scholar
Navarro, M. and Gull, K. (2001). A pol I transcriptional body associated with VSG mono-allelic expression in Trypanosoma brucei . Nature 414, 759–763.Google Scholar
Ngoyi, M., Menten, J., Pyana, P. P., Philippe, B. and Lejon, V. (2013). Stage determination in sleeping sickness: comparison of two cell counting and two parasite detection techniques. Tropical Medicine and International Health 18, 778–782.Google Scholar
Njiokou, F., Nimpaye, H., Simo, G., Njitchouang, G. R., Asonganyi, T., Cuny, G. and Herder, S. (2010). Domestic animals as potential reservoir hosts of Trypanosoma brucei gambiense in sleeping sickness foci in Cameroon. Parasite (Paris, France) 17, 61–66.Google Scholar
Obishakin, E., de Trez, C. and Magez, S. (2014). Chronic Trypanosoma congolense infections in mice cause a sustained disruption of the B cell homeostasis in the bone marrow and spleen. Parasite Immunology 36(5), 187–198.Google Scholar
Oka, M., Yabu, Y., Ito, Y. and Takayanagi, T. (1988). Polyclonal B-cell stimulative and immunosuppressive activities at different developmental stages of Trypanosoma gambiense . Microbial Immunology 32, 1175–1177.Google Scholar
Oliveira, J. B., Hernández-Gamboa, J., Jiménez-Alfaro, C., Zeledón, R., Blandón, M. and Urbina, A (2009). First report of Trypanosoma vivax infection in dairy cattle from Costa Rica. Veterinary Parasitology 163, 136–139.Google Scholar
Onah, D. N. and Wakelin, D. (2000). Murine model study of the practical implication of trypanosome-induced immunosuppression in vaccine-based disease control programmes. Veterinary Immunology and Immunopathology 74, 271–284.Google Scholar
Ormerod, W. E. (1970). The pathogenesis and pathology of trypanosomiasis in man. In: Mulligan, HW, Potts, WH, Kershaw, WE, eds., The African Trypanosomiasis, Allen and Unwin, Ltd London, pp. 587–613.Google Scholar
Paulnock, D. M., Freeman, B. E. and Mansfield, J. M. (2010). Modulation of innate immunity by African trypanosomes. Parasitology 137, 2051–2063.Google Scholar
Pays, E., Lips, S., Nolan, D., Vanhamme, L. and Pérez-Morga, D. (2001). The VSG expression sites of Trypanosoma brucei: multipurpose tools for the adaptation of the parasite to mammalian hosts. Molecular and Biochemical Parasitology 114, 1–16.CrossRefGoogle ScholarPubMed
Pays, E., Vanhollebeke, B., Vanhamme, L., Paturiaux-Hanocq, F., Nolan, D. P. and Perez-Morga, D. (2006). Trypanolytic factor of human serum. Nature Reviews in Microbiology 161, 309–315.Google Scholar
Pays, E., Vanhollebeke, B., Uzureau, P., Lecordier, L. and Pérez-Morga, D. (2014). The molecular arms race between African trypanosomes and humans. Nature Reviewsin Microbiology 12, 575–584.Google Scholar
Radwanska, M., Magez, S., Dumont, N., Pays, A., Nolan, D. and Pays, E. (2000). Antibodies raised against the flagellar pocket fraction of Trypanosoma brucei preferentially recognize HSP60 in cDNA expression library. Parasite Immunology 22, 639–650.Google Scholar
Radwanska, M., Claes, F., Magez, S., Magnus, E., Perez-morga, D., Pays, E. and Büscher, P. (2002). Novel primer sequences for polymerase chain reaction–based detection of Trypanosoma brucei gambiense. American Journal of Tropical Medicine and Hygiene 67, 289–295.Google Scholar
Radwanska, M., Guirnalda, P., De Trez, C., Ryffel, B., Black, S. and Magez, S. (2008). Trypanosomiasis-induced B cell apoptosis results in loss of protective anti-parasite antibody responses and abolishment of vaccine-induced memory responses. PLoS Pathogens 4, e1000078.Google Scholar
Raper, J., Nussenzweig, V. and Tomlinson, S. (1996). The main lytic factor of Trypanosoma brucei brucei in normal human serum is not high density lipoprotein. Journal of Experimental Medicine 183, 1023–1029.CrossRefGoogle Scholar
Raper, J., Fung, R., Ghiso, J., Nussenzweig, V. and Tomlinson, S. (1999). Characterization of a Novel Trypanosome Lytic Factor from Human Serum Characterization of a Novel Trypanosome Lytic Factor from Human Serum. 67.Google Scholar
Raper, J., Portela, M. P., Lugli, E., Frevert, U. and Tomlinson, S. (2001). Trypanosome lytic factors: novel mediators of human innate immunity. Current Opinion in Microbiology 4, 402–408.Google Scholar
Reid, S. A and Copeman, D. B. (2000). Surveys in Papua New Guinea to detect the presence of Trypanosoma evansi infection. Australian Veterinary Journal 78, 843–845.Google Scholar
Reuner, B., Vassella, E., Yutzy, B. and Boshart, M. (1997). Cell density triggers slender to stumpy differentiation of Trypanosoma brucei bloodstream forms in culture. Molecular and biochemical parasitology 90, 269–280.Google Scholar
Rico, E., Rojas, F., Mony, B. M., Szoor, B., Macgregor, P. and Matthews, K. R. (2013). Bloodstream form pre-adaptation to the tsetse fly in Trypanosoma brucei . Frontiers in Cellular and Infection Microbiology 3, 78.Google Scholar
Rifkin, M. R. (1978). Identification of the trypanocidal factor in normal human serum: high density lipoprotein. Proceedings of the National Academy of Sciences of the United States of America 75, 3450–3454.Google Scholar
Robinson, N. P., Burman, N. and Melville, S. E. (1999). Predominance of Duplicative VSG Gene Conversion in Antigenic Variation in African Trypanosomes Predominance of Duplicative VSG Gene Conversion in Antigenic Variation in African Trypanosomes.Google Scholar
Roditi, I. and Lehane, M. J. (2008). Interactions between trypanosomes and tsetse flies. Current Opinion in Microbiology 11, 345–351.Google Scholar
Rudenko, G. (2011). African trypanosomes: the genome and adaptations for immune evasion. Essays in Biochemistry 51, 47–62.Google Scholar
Salmon, D., Bachmaier, S., Krumbholz, C., Kador, M., Gossmann, J. A, Uzureau, P., Pays, E. and Boshart, M. (2012 a). Cytokinesis of Trypanosoma brucei bloodstream forms depends on expression of adenylyl cyclases of the ESAG4 or ESAG4-like subfamily. Molecular Microbiology 84, 225–242.Google Scholar
Salmon, D., Vanwalleghem, G., Morias, Y., Denoeud, J., Krumbholz, C., Lhommé, F., Bachmaier, S., Kador, M., Gossmann, J., Dias, F. B. S., De Muylder, G., Uzureau, P., Magez, S., Moser, M., De Baetselier, P., Van Den Abbeele, J., Beschin, A., Boshart, M. and Pays, E. (2012 b). Adenylate cyclases of Trypanosoma brucei inhibit the innate immune response of the host. Science (New York, N.Y.) 337, 463–466.Google Scholar
Schleifer, K. W. and Mansfield, J. M. (1993). Suppressor macrophages in African trypanosomiasis inhibit T cell proliferative responses by nitric oxide and prostaglandins. Journal of Immunology 151, 5492–5503.Google Scholar
Schwede, A. and Carrington, M. (2010). Bloodstream form Trypanosome plasma membrane proteins: antigenic variation and invariant antigens. Parasitology 137, 2029–2039.Google Scholar
Shiflett, A., Faulkner, S., Cotlin, L., Widener, J., Stephens, N. and Hajduk, S. (2007). African Trypanosomes: intracellular trafficking of host defense molecules. Journal of Eukaryotic Microbiology 54, 18–21.Google Scholar
Silva, R. A., Arosemena, N. A. E., Herrera, H. M., Sahib, C. A. and Ferreira, M. S. J. (1995). Oytbreak of trypanosomosis due to Trypanosoma evansi in horses of Pantanal Mato-grossense, Brazil. Veterinary Parasitology 60, 167–171.Google Scholar
Simarro, P. P., Diarra, A., Ruiz Postigo, J. A., Franco, J. R. and Jannin, J. G. (2011). The human African trypanosomiasis control and surveillance programme of the World Health Organization 2000–2009: the way forward. PLoS Neglected Tropical Diseases 5, e1007.CrossRefGoogle ScholarPubMed
Simarro, P. P., Cecchi, G., Franco, J. R., Paone, M., Diarra, A., Ruiz-Postigo, J. A., Fèvre, E. M., Mattioli, R. C. and Jannin, J. G. (2012). Estimating and mapping the population at risk of sleeping sickness. PLoS Neglected Tropical Diseases 6, e1859.Google Scholar
Sternberg, J. M. (2004). Human African trypanosomiasis: clinical presentation and immune response. Parasite Immunology 26, 469–476.Google Scholar
Szöőr, B., Dyer, N. A., Ruberto, I., Acosta-Serrano, A. and Matthews, K. R. (2013). Independent pathways can transduce the life-cycle differentiation signal in Trypanosoma brucei . PLoS Pathogens 9, e1003689.Google Scholar
The Chimpanzee Sequencing and Analysis Consortium (2005). Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437, 69–87.Google Scholar
Thomson, R., Genovese, G., Canon, C., Kovacsics, D., Higgins, M. K., Carrington, M., Winkler, C. A., Kopp, J., Rotimi, C., Adeyemo, A., Doumatey, A., Ayodo, G., Alper, S. L., Pollak, M. R., Friedman, D. J. and Raper, J. (2014). Evolution of the primate trypanolytic factor APOL1. Proceedings of the National Academy of Sciences of the United States of America 111, E2130–E2139.Google Scholar
Tomlinson, S. and Raper, J. (1996). The lysis of Trypanosoma brucei brucei by human serum. Nature biotechnology 14, 717–721.Google Scholar
Tyler, K. M., Higgs, P. G., Matthews, K. R. and Gull, K. (2001). Limitation of Trypanosoma brucei parasitaemia results from density-dependent parasite differentiation and parasite killing by the host immune response. Proceedings. Biological Sciences/The Royal Society 268, 2235–2243.Google Scholar
Uzureau, P., Uzureau, S., Lecordier, L., Fontaine, F., Tebabi, P., Homblé, F., Grélard, A., Zhendre, V., Nolan, D. P., Lins, L., Crowet, J.-M., Pays, A., Felu, C., Poelvoorde, P., Vanhollebeke, B., Moestrup, S. K., Lyngsø, J., Pedersen, J. S., Mottram, J. C., Dufourc, E. J., Pérez-Morga, D. and Pays, E. (2013). Mechanism of Trypanosoma brucei gambiense resistance to human serum. Nature 501, 430–434.Google Scholar
Van Xong, H., Vanhamme, L., Chamekh, M., Chimfwembe, C. E., Van Den Abbeele, J., Pays, A., Van Meirvenne, N., Hamers, R., De Baetselier, P., Pays, E. and Gene, B. R. S. (1998). A VSG expression site – associated gene confers resistance to human serum in Trypanosoma rhodesiense Prince Leopold Institute of Tropical Medicine. Cell 95, 839–846.Google Scholar
Vanhamme, L., Pays, E., McCulloch, R. and Barry, J. D. (2001 a). An update on antigenic variation in African trypanosomes. Trends in Parasitology 17, 338–343.Google Scholar
Vanhamme, L., Pays, E., McCulloch, R. and Barry, J. D. (2001 b). An update on antigenic variation in African trypanosomes. Trends in Parasitology 17, 338–343.Google Scholar
Vanhamme, L., Paturiaux-Hanocq, F., Poelvoorde, P., Nolan, D. P., Lins, L., Van Den Abbeele, J., Pays, A., Tebabi, P., Van Xong, H., Jacquet, A., Moguilevsky, N., Dieu, M., Kane, J. P., De Baetselier, P., Brasseur, R. and Pays, E. (2003). Apolipoprotein L-I is the trypanosome lytic factor of human serum. Nature 422, 83–87.Google Scholar
Vanhollebeke, B. and Pays, E. (2010 a). The trypanolytic factor of human serum: many ways to enter the parasite, a single way to kill. Molecular Microbiology 76, 806–814.Google Scholar
Vanhollebeke, B. and Pays, E. (2010 b). The trypanolytic factor of human serum: many ways to enter the parasite, a single way to kill. Molecular Microbiology 76, 806–814.Google Scholar
Vanhollebeke, B., De Muylder, G., Nielsen, M. J., Pays, A., Tebabi, P., Dieu, M., Raes, M., Moestrup, S. K. and Pays, E. (2008). A haptoglobin-hemoglobin receptor conveys innate immunity to Trypanosoma brucei in humans. Science (New York, N.Y.) 320, 677–681.Google Scholar
Vassella, E., Reuner, B., Yutzy, B. and Boshart, M. (1997). Differentiation of African trypanosomes is controlled by a density sensing mechanism which signals cell cycle arrest via the cAMP pathway. Journal of Cell Science 110(Pt 2), 2661–2671.Google Scholar
WHO (2012). Report of a WHO meeting on elimination of African trypanosomiasis (Trypanosoma brucei gambiense).Google Scholar