Abstract
The immunology of African trypanosomiasis is reviewed and reexamined in light of newer findings over the past decade. New paradigms of host resistance include information that the variant surface glycoprotein specific Ab response is not linked, alone, to overall resistance, and that Th1 cells, IFN-γ and macrophages play a powerful role in providing tissue-specific protection against trypanosomes. New questions concerning the specific role of “antigen pattern” recognition of the VSG coat by B cells, and the potentially interesting role of the trypanosome T lymphocyte triggering factor (TLTF), are addressed. Overall this chapter is aimed at providing the reader with new perspectives on the immunobiology of African sleeping sickness.
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References
Abbas, A. K., A. H. Lichtman, and J. S. Pober. 2000. Cellular and Molecular Immunology, 4th Edition: 359.
Agur, Z., D. Abiri, and L. H. Van der Ploeg. 1989. Ordered appearance of antigenic variants of African trypanosomes explained in a mathematical model based on a stochastic switch process and immune-selection against putative switch intermediates. Proceedings of the National Academy of Sciences of the United States of America 86:9626.
Baltz, T., C. Giroud, D. Baltz, C. Roth, A. Raibaud, and H. Eisen. 1986. Stable expression of two variable surface glycoproteins by cloned Trypanosoma equiperdum. Nature 319:602.
Munoz-Jordan, J. L., K. P. Davies, and G. A. Cross. 1996. Stable expression of mosaic coats of variant surface glycoproteins in Trypanosoma brucei. Science 272:1795.
Bakhiet, M., P. Buscher, R. A. Harris, K. Kristensson, H. Wigzell, and T. Olsson. 1996. Different Trypanozoan Species Possess Cd8 Dependent Lymphocyte Triggering Factor-Like Activity. Immunology Letters 50:71.
—, E. Mix, K. Kristensson, H. Wigzell, and T. Olsson. 1993. T cell activation by a Trypanosoma brucei brucei-derived lymphocyte triggering factor is dependent on tyrosine protein kinases but not on protein kinase C and A. European Journal of Immunology 23: 1535.
—, T. Olsson, C. Edlund, B. Hojeberg, K. Holmberg, J. Lorentzen, and K. Kristensson. 1993. A Trypanosoma brucei brucei-derived factor that triggers CD8+ lymphocytes to interferon-gamma secretion: purification, characterization and protective effects in vivo by treatment with a monoclonal antibody against the factor. Scand J Immunol 37:165.
—, T. Olsson, J. Mhlanga, P. Buscher, N. Lycke, P. H. Vandermeide, and K. Kristensson. 1996. Human and Rodent Interferon-Gamma As a Growth Factor For Trypanosoma Brucei. European Journal of Immunology 26: 1359.
—, T. Olsson, P. Van der Meide, and K. Kristensson. 1990. Depletion of CD8+ T cells suppresses growth of Trypanosoma brucei brucei and interferongamma production in infected rats. Clin Exp Immunol 81:195.
Blum, J. L., J. A. Down, A. M. Gurnett, M. Carrington, M. J. Turner, and D. C. Wiley. 1993. A structural motif in the variant surface glycoproteins of Trypanosoma brucei. Nature 362:603.
Borst, P., and G. Rudenko. 1994. Antigenic variation in African trypanosomes. Science 264:1872.
—, G. Rudenko, M. C. Taylor, P. A. Blundell, F. Vanleeuwen, W. Bitter, M. Cross, and R. McCulloch. 1996. Antigenic Variation In Trypanosomes. Archives of Medical Research 27:379.
Campbell, G. H., K. M. Esser, and S. M. Phillips. 1982. Parasite-(antigen) specific stimulation of B and T cells in African trypanosomiasis. J Immunol 129:1272.
Cross, G. A. 1975. Identification, purification and properties of clone-specific glycoprotein antigens constituting the surface coat of Trypanosoma brucei. Parasitology 71:393.
—. 1990. Cellular and genetic aspects of antigenic variation in trypanosomes. Annu Rev Immunol 8:83.
—. 1996. Antigenic variation in trypanosomes: secrets surface slowly. Bioessays 18:283.
Darji, A., A. Beschin, M. Sileghem, H. Heremans, L. Brys, and P. Debaetselier. 1996. In Vitro Simulation Of Immunosuppression Caused By Trypanosoma Brucei—Active Involvement Of Gamma Interferon and Tumor Necrosis Factor In the Pathway Of Suppression. Infection & Immunity 64:1937.
De Gee, A. L., and J. M. Mansfield. 1984. Genetics of resistance to the African trypanosomes. IV. Resistance of radiation chimeras to Trypanosoma rhodesiense infection. Cell Immunol 87:85.
—, R. F. Levine, and J. M. Mansfield. 1988. Genetics of resistance to the African trypanosomes. VI. Heredity of resistance and variable surface glycoproteinspecific immune responses. J Immunol 140:283.
Eltayeb, R., A. Sharafeldin, R. Jaster, T. Bittorf, E. Mix, and M. Bakhiet. 2000. Trypanosoma brucei brucei induces interferon-gamma expression in rat dorsal root ganglia cells via a tyrosine kinase-dependent pathway. Journal of Infectious Diseases 181:400.
Esser, K. M., and M. J. Schoenbechler. 1985. Expression of two variant surface glycoproteins on individual African trypanosomes during antigen switching. Science 229:190.
Field, M. C., and J. C. Boothroyd. 1996. Sequence divergence in a family of variant surface glycoprotein genes from trypanosomes: coding region hypervariability and downstream recombinogenic repeats. Journal of Molecular Evolution 42:500.
Finerty, J. F., E. P. Krehl, and R. L. McKelvin. 1978. Delayed-type hypersensitivity in mice immunized with Trypanosoma rhodesiense antigens. Infection & Immunity 20:464.
Hamadien, M., N. Lycke, and M. Bakhiet. 1999. Induction of the trypanosome lymphocyte-triggering factor (TLTF) and neutralizing antibodies to the TLTF in experimental african trypanosomiasis. Immunology 96:606.
Hertz, C. J., H. Filutowicz, and J. M. Mansfield. 1998. Resistance to the African trypanosomes is IFN-gamma dependent. Journal of Immunology 161:6775.
—, and J. M. Mansfield. 1999. IFN-gamma-dependent nitric oxide production is not linked to resistance in experimental African trypanosomiasis. Cellular Immunology 192:24.
Hill, K. L., N. R. Hutchings, P. M. Grandgenett, and J. E. Donelson. 2000. T Lymphocyte-triggering factor of African trypanosomes is associated with the flagellar fraction of the cytoskeleton and represents a new family of proteins that are present in several divergent eukaryotes. Journal of Biological Chemistry 275:39369.
—, N. R. Hutchings, D. G. Russell, and J. E. Donelson. 1999. A novel protein targeting domain directs proteins to the anterior cytoplasmic face of the flagellar pocket in African trypanosomes. Journal of Cell Science 112:3091.
Inverso, J. A., A. L. De Gee, and J. M. Mansfield. 1988. Genetics of resistance to the African trypanosomes. VII. Trypanosome virulence is not linked to variable surface glycoprotein expression. J Immunol 140:289.
Levine, R. F., and J. M. Mansfield. 1981. Genetics of resistance to African trypanosomes: role of the H-2 locus in determining resistance to infection with Trypanosoma rhodesiense. Infect Immun 34:513.
Lucas, R., S. Magez, B. Songa, A. Darji, R. Hamers, and P. de-Baetselier. 1993. A role for TNF during African trypanosomiasis: involvement in parasite control, immunosuppression and pathology. Res Immunol 144:370.
—, S. Magez. R. De-Leys, L. Fransen, J. P. Scheerlinck, M. Rampelberg, E. Sablon, and P. De-Baetselier. 1994. Mapping the lectin-like activity of tumor necrosis factor. Science 263:814.
Magez, S., M. Geuskens, A. Beschin, H. Delfavero, H. Verschueren, R. Lucas, E. Pays, and P. Debaetselier. 1997. Specific Uptake Of Tumor Necrosis Factor-Alpha Is Involved In Growth Control Of Trypanosoma Brucei. Journal of Cell Biology 137:715.
—, M. Radwanska, A. Beschin, K. Sekikawa, and P. De Baetselier. 1999. Tumor necrosis factor alpha is a key mediator in the regulation of experimental Trypanosoma brucei infections. Infection & Immunity 67:3128.
Mansfield, J. M. 1990. Immunology of African trypanosomiasis. In Modern Parasite Biology: Cellular, Immunological and Molecular Aspects. D. J. Wyler, ed. W. H. Freeman and Co., New York, p. 222.
—, 1994. T-cell responses to the trypanosome variant surface glycoprotein: A new paradigm? Parasitol Today 10:267.
—, 1995. Immunobiology of African trypanosomiasis: A revisionist view. In Molecular Approaches to Parasitology. J. C. Boothroyd, and R. Komuniecki, eds. Wiley-Liss, New York, p. 477.
—, and O. Bagasra. 1978. Lymphocyte function in experimental African trypanosomiasis. I. B cell responses to helper T cell-independent and-dependent antigens. J Immunol 120:759.
—, and J. P. Kreier. 1972. Tests for antibody-and cell-mediated hypersensitivity to trypanosome antigens in rabbits infected with Trypanosoma congolense. Infect Immun 6:62.
—, R. F. Levine, W. L. Dempsey, S. R. Wellhausen, and C. T. Hansen. 1981. Lymphocyte function in experimental African trypanosomiasis. IV. Immunosuppression and suppressor cells in the athymic nu/nu mouse. Cell Immunol 63:210.
—, and M. Olivier. 2001. Immune evasion by parasites. In Infection and Immunity. A. Sher, and S. Kaufmann, eds. ASM Press.
—, D. M. Paulnock, C. J. Hertz, H. Filutowicz, L. R. Schopf, and J. Sypeck. 2001. IFNg-independent IL-12 production during trypanosome infection directs the outgrowth of highly polarized Th1 cell responses. Journal of Immunology Submitted.
—, and J. H. Wallace. 1974. Suppression of cell-mediated immunity in experimental African trypanosomiasis. Infect Immun 10:335.
Millar, A. E., J. Sternberg, C. McSharry, X. Q. Wei, F. Y. Liew, and C. M. Turner. 1999. T-cell responses during Trypanosoma brucei infections in mice deficient in inducible nitric oxide synthase. Infection & Immunity 67:3334.
Mnaimneh, S., M. Geffard, B. Veyret, and P. Vincendeau. 1997. Albumin Nitrosylated By Activated Macrophages Possesses Antiparasitic Effects Neutralized By Anti-No-Acetylated-Cysteine Antibodies. Journal of Immunology 158:308.
Mulligan, H. W. 1970. The African trypanosomiases, New York.
Olsson, T., M. Bakhiet, C. Edlund, B. Hojeberg, P. H. Van der Meide, and K. Kristensson. 1991. Bidirectional activating signals between Trypanosoma brucei and CD8+ T cells: a trypanosome-released factor triggers interferon-gamma production that stimulates parasite growth. Eur J Immunol 21:2447.
—, M. Bakhiet, B. Hojeberg, A. Ljungdahl, C. Edlund, G. Andersson, H. P. Ekre, W. P. Fung-Leung, T. Mak, H. Wigzell, U. Fiszer, and K. Kristensson. 1993. CD8 is critically involved in lymphocyte activation by a T. brucei brucei-released molecule. Cell 72:715.
—, M. Bakhiet, and K. Kristensson. 1992. Interactions between Trypanosoma brucei and CD8+ T cells. Parasitol Today 8:237.
Paulnock, D. M., C. Smith, and J. M. Mansfield. 1989. Antigen presenting cell function in African trypanosomiasis. Alan R Liss, Inc, New York 0: 135.
Reinitz, D. M., B. D. Aizenstein, and J. M. Mansfield. 1992. Variable and conserved structural elements of trypanosome variant surface glycoproteins. Mol Biochem Parasitol 51:119.
—, and J. M. Mansfield. 1988. Independent regulation of B cell responses to surface and subsurface epitopes of African trypanosome variable surface glycoproteins. J Immunol 141:620.
—, and J. M. Mansfield. 1990. T-cell-independent and T-cell-dependent B-cell responses to exposed variant surface glycoprotein epitopes in trypanosomeinfected mice. Infect Immun 58:2337.
Sternberg, J., and F. McGuigan. 1992. Nitric oxide mediates suppression of T cell responses in murine Trypanosoma brucei infection. Eur J Immunol 22:2741.
Sacks, D. L., G. Bancroft, W. H. Evans, and B. A. Askonas. 1982. Incubation of trypanosome-derived mitogenic and immunosuppressive products with peritoneal macrophages allows recovery of biological activities from soluble parasite fractions. Infect Immun 36:160.
Schleifer, K. W., H. Filutowicz, L. R. Schopf, and J. M. Mansfield. 1993. Characterization of T helper cell responses to the trypanosome variant surface glycoprotein. J Immunol 150:2910.
—, and J. M. Mansfield. 1993. Suppressor macrophages in African trypanosomiasis inhibit T cell proliferative responses by nitric oxide and prostaglandins. J Immunol 151:5492.
Schopf, L. R.. H. Filutowicz, X. J. Bi, and J. M. Mansfield. 1998. Interleukin-4-dependent immunoglobulin G1 isotype switch in the presence of a polarized antigenspecific Th1-cell response to the trypanosome variant surface glycoprotein. Infection & Immunity 66:451.
Timmers, H. T., T. de Lange, J. M. Kooter, and P. Borst. 1987. Coincident multiple activations of the same surface antigen gene in Trypanosoma brucei. Journal of Molecular Biology 194:81.
Turner, C. M. R. 1997. Trypanosomes With Multicoloured Coats. Parasitology Today 13:247.
Vaidya, T.. M. Bakhiet, K. L. Hill, T. Olsson, K. Kristensson, and J. E. Donelson. 1997. The Gene For a T Lymphocyte Triggering Factor From African Trypanosomes. Journal of Experimental Medicine 186:433.
Van der Ploeg, L. H., K. Gottesdiener, and M. G. Lee. 1992. Antigenic variation in African trypanosomes. Trends Genet 8:452.
Vickerman, K., and A. G. Luckins. 1969. Localization of variable antigens in the surface coat of Trypanosoma brucei using ferritin conjugated antibody. Nature 224:1125.
Vincendeau, P., S. Daulouede, B. Veyret, M. L. Darde, B. Bouteille, and J. L. Lemesre. 1992. Nitric oxide-mediated cytostatic activity on Trypanosoma brucei gambiense and Trypanosoma brucei brucei. Exp Parasitol 75:353.
Wellhausen, S. R., and J. M. Mansfield. 1979. Lymphocyte function in experimental African trypanosomiasis. II. Splenic suppressor cell activity. J Immunol 122:818.
—, and J. M. Mansfield. 1980. Characteristics of the splenic suppressor cell-target cell interaction in experimental African trypanosomiasis. Cell Immunol 54:414.
—, and J. M. Mansfield. 1980. Lymphocyte function in experimental African trypanosomiasis. III. Loss of lymph node cell responsiveness. J Immunol 124:1183.
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Mansfield, J.M., Davis, T.H., Dubois, M.E. (2002). Immunobiology of African Trypanosomiasis: New Paradigms, Newer Questions. In: The African Trypanosomes. World Class Parasites, vol 1. Springer, Boston, MA. https://doi.org/10.1007/0-306-46894-8_7
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DOI: https://doi.org/10.1007/0-306-46894-8_7
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