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The endless race between Trypanosoma cruzi and host immunity: lessons for and beyond Chagas disease

  • Caroline Junqueira (a1) (a2), Braulia Caetano (a3), Daniella C. Bartholomeu (a4), Mariane B. Melo (a3), Catherine Ropert (a1), Maurício M. Rodrigues (a5) and Ricardo T. Gazzinelli (a1) (a2) (a3)...


Infection with the protozoan parasite Trypanosoma cruzi, the agent of Chagas disease, is characterised by a variable clinical course – from symptomless cases to severe chronic disease with cardiac and/or gastrointestinal involvement. The variability in disease outcome has been attributed to host responses as well as parasite heterogeneity. In this article, we review studies indicating the importance of immune responses as key determinants of host resistance to T. cruzi infection and the pathogenesis of Chagas disease. Particular attention is given to recent studies defining the role of cognate innate immune receptors and immunodominant CD8+ T cells that recognise parasite components – both crucial for host–parasite interaction and disease outcome. In light of these studies we speculate about parasite strategies that induce a strong and long-lasting T-cell-mediated immunity but at the same time allow persistence of the parasite in the vertebrate host. We also discuss what we have learned from these studies for increasing our understanding of Chagas pathogenesis and for the design of new strategies to prevent the development of Chagas disease. Finally, we highlight recent studies employing a genetically engineered attenuated T. cruzi strain as a vaccine shuttle that elicits potent T cell responses specific to a tumour antigen and protective immunity against a syngeneic melanoma cell line.


Corresponding author

*Corresponding author: Ricardo T. Gazzinelli, Laboratório de Immunopatologia, Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Avenida Augusto de Lima 1715, Belo Horizonte, MG 30190-002, Brazil. E-mail:


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1Chagas, C. (1909) Nova tripanozomiase humana. Memórias do Instituto Oswaldo Cruz 1, 159-218
2Evans, A.S. (1976) Causation and disease: the Henle-Koch postulates revisited. Journal of Biology and Medicine 49, 175-195
3Coura, J.R. and Dias, J.C. (2009) Epidemiology, control and surveillance of Chagas disease: 100 years after its discovery. Memórias do Instituto Oswaldo Cruz 1, 31-40
4Brener, Z. and Gazzinelli, R.T. (1997) Immunological control of Trypanosoma cruzi infection and pathogenesis of Chagas' disease. International Archives of Allergy and Applied Immunology 114, 103-110
5Tarleton, R.L. (2007) Immune system recognition of Trypanosoma cruzi. Current Opinion in Immunology 19, 430-434
6El-Sayed, N.M. et al. (2005) The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease. Science 309, 409-415
7Khaw, M. and Panosian, C.B. (1995) Human antiprotozoal therapy: past, present, and future. Clinical Microbiology Reviews 8, 427-439
8Urbina, J.A. (2010) Specific chemotherapy of Chagas disease: relevance, current limitations and new approaches. Acta Tropica 115, 55-68
9Guhl, F. et al. (1997) Trypanosoma cruzi DNA in human mummies. Lancet 349, 1370
10Pena, S.D.J. and Santos, F.R. (2000) Origen de los Amerindios. Investigacion y Ciencia 287, 48-54
11de Freitas, J.M. et al. (2006) Ancestral genomes, sex, and the population structure of Trypanosoma cruzi. PLoS Pathogens 2, e24
12Brener, Z. (1973) Biology of Trypanosoma cruzi. Annual Review of Microbiology 27, 347-382
13Moncayo, A. and Silveira, A.C. (2009) Current epidemiological trends for Chagas disease in Latin America and future challenges in epidemiology, surveillance and health policy. Memórias do Instituto Oswaldo Cruz 1, 17-30
14PAHO (2007) Technical Guidelines for Prevention and Control of Chagas Disease [PAHO/MSF Regional Consultation on the Organization and Structure of Health Care (IEC) on Congenital Chagas Disease].
15Rassi, A. Jr, Rassi, A. and Marin-Neto, J.A. (2010) Chagas disease. Lancet 375, 1388-1402
16Gutierrez, F.R. et al. (2009) The role of parasite persistence in pathogenesis of Chagas heart disease. Parasite Immunology 31, 673-685
17Bilate, A.M. and Cunha-Neto, E. (2008) Chagas disease cardiomyopathy: current concepts of an old disease. Revista do Instituto de Medicina Tropical de São Paulo 50, 67-74
18Coura, J.R. and Borges-Pereira, J. (2010) Chagas disease: 100 years after its discovery. A systemic review. Acta Tropica 115, 5-13
19Leon, J.S. and Engman, D.M. (2003) The significance of autoimmunity in the pathogenesis of Chagas heart disease. Frontiers in Bioscience 8, e315-e322
20Cunha-Neto, E. et al. (2006) Induction of cardiac autoimmunity in Chagas heart disease: a case for molecular mimicry. Autoimmunity 39, 41-54
21Jones, E.M. et al. (1993) Amplification of a Trypanosoma cruzi DNA sequence from inflammatory lesions in human chagasic cardiomyopathy. American Journal of Tropical Medicine and Hygiene 48, 348-357
22Higuchi, M.L. et al. (1993) Correlation between Trypanosoma cruzi parasitism and myocardial inflammatory infiltrate in human chronic chagasic myocarditis: light microscopy and immunohistochemical findings. Cardiovascular Pathology 2, 101-106
23Vago, A.R. et al. (1996) PCR detection of Trypanosoma cruzi DNA in oesophageal tissues of patients with chronic digestive Chagas' disease. Lancet 348, 891-892
24Macedo, A.M., Oliveira, R.P. and Pena, S.D. (2002) Chagas disease: role of parasite genetic variation in pathogenesis. Expert Reviews in Molecular Medicine 4, 1-16
25Tarleton, R.L. (2003) Chagas disease: a role for autoimmunity? Trends in Parasitology 19, 447-451
26Andrade, Z.A. (1991) Pathogenesis of Chagas' disease. Research in Immunology 142, 126-129
27Golgher, D. and Gazzinelli, R.T. (2004) Innate and acquired immunity in the pathogenesis of Chagas disease. Autoimmunity 37, 399-409
28Takeuchi, O. and Akira, S. (2010) Pattern recognition receptors and inflammation. Cell 140, 805-820
29Dobrovolskaia, M.A. and Vogel, S.N. (2002) Toll receptors, CD14, and macrophage activation and deactivation by LPS. Microbes and Infection 4, 903-914
30Lien, E. and Ingalls, R.R. (2002) Toll-like receptors. Critical Care Medicine 30, S1-S11
31Gazzinelli, R.T., Ropert, C. and Campos, M.A. (2004) Role of the Toll/interleukin-1 receptor signaling pathway in host resistance and pathogenesis during infection with protozoan parasites. Immunological Reviews 201, 9-25
32Gay, N.J. and Keith, F.J. (1991) Drosophila Toll and IL-1 receptor. Nature 351, 355-356
33Rock, F.L. et al. (1998) A family of human receptors structurally related to Drosophila Toll. Proceedings of the National Academy of Sciences of the United States of America 95, 588-593
34O'Neill, L.A., Fitzgerald, K.A. and Bowie, A.G. (2003) The Toll-IL-1 receptor adaptor family grows to five members. Trends in Immunology 24, 286-290
35Takeuchi, O. and Akira, S. (2002) MyD88 as a bottle neck in Toll/IL-1 signaling. Current Topics in Microbiology and Immunology 270, 155-167
36Fitzgerald, K.A. et al. (2001) Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction. Nature 413, 78-83
37Fitzgerald, K.A. et al. (2003) LPS-TLR4 signaling to IRF-3/7 and NF-kappaB involves the toll adapters TRAM and TRIF. Journal of Experimental Medicine 198, 1043-1055
38Yamamoto, M. et al. (2002) Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4. Nature 420, 324-329
39Horng, T. et al. (2002) The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors. Nature 420, 329-333
40Almeida, I.C. and Gazzinelli, R.T. (2001) Proinflammatory activity of glycosylphosphatidylinositol anchors derived from Trypanosoma cruzi: structural and functional analyses. Journal of Leukocyte Biology 70, 467-477
41Almeida, I.C. et al. (2000) Highly purified glycosylphosphatidylinositols from Trypanosoma cruzi are potent proinflammatory agents. EMBO Journal 19, 1476-1485
42Campos, M.A. et al. (2001) Activation of Toll-like receptor-2 by glycosylphosphatidylinositol anchors from a protozoan parasite. Journal of Immunology 167, 416-423
43Ropert, C. et al. (2003) Inhibition of a p38/stress-activated protein kinase-2-dependent phosphatase restores function of IL-1 receptor-associate kinase-1 and reverses Toll-like receptor 2- and 4-dependent tolerance of macrophages. Journal of Immunology 171, 1456-1465
44Gazzinelli, R.T. and Denkers, E.Y. (2006) Protozoan encounters with Toll-like receptor signalling pathways: implications for host parasitism. Nature Reviews Immunology 6, 895-906
45Campos, M.A. et al. (2004) Impaired production of proinflammatory cytokines and host resistance to acute infection with Trypanosoma cruzi in mice lacking functional myeloid differentiation factor 88. Journal of Immunology 172, 1711-1718
46Oliveira, A.C. et al. (2004) Expression of functional TLR4 confers proinflammatory responsiveness to Trypanosoma cruzi glycoinositolphospholipids and higher resistance to infection with T. cruzi. Journal of Immunology 173, 5688-5696
47Thieblemont, N. and Wright, S.D. (1997) Mice genetically hyporesponsive to lipopolysaccharide (LPS) exhibit a defect in endocytic uptake of LPS and ceramide. Journal of Experimental Medicine 185, 2095-2100
48Shoda, L.K. et al. (2001) DNA from protozoan parasites Babesia bovis, Trypanosoma cruzi, and T. brucei is mitogenic for B lymphocytes and stimulates macrophage expression of interleukin-12, tumor necrosis factor alpha, and nitric oxide. Infection and Immunity 69, 2162-2171
49Krieg, A.M. (2002) CpG motifs in bacterial DNA and their immune effects. Annual Review of Immunology 20, 709-760
50Bartholomeu, D.C. et al. (2008) Recruitment and endo-lysosomal activation of TLR9 in dendritic cells infected with Trypanosoma cruzi. Journal of Immunology 181, 1333-1344
51Lorenzi, H.A., Robledo, G. and Levin, M.J. (2006) The VIPER elements of trypanosomes constitute a novel group of tyrosine recombinase-enconding retrotransposons. Molecular and Biochemical Parasitology 145, 184-194
52Xiong, Y. and Eickbush, T.H. (1990) Origin and evolution of retroelements based upon their reverse transcriptase sequences. EMBO Journal 9, 3353-3362
53Bafica, A. et al. (2006) Cutting edge: TLR9 and TLR2 signaling together account for MyD88-dependent control of parasitemia in Trypanosoma cruzi infection. Journal of Immunology 177, 3515-3519
54Hemmi, H. et al. (2000) A Toll-like receptor recognizes bacterial DNA. Nature 408, 740-745
55Chessler, A.D. et al. (2008) A novel IFN regulatory factor 3-dependent pathway activated by trypanosomes triggers IFN-beta in macrophages and fibroblasts. Journal of Immunology 181, 7917-7924
56Chessler, A.D. et al. (2009) Trypanosoma cruzi triggers an early type I IFN response in vivo at the site of intradermal infection. Journal of Immunology 182, 2288-2296
57Kayama, H. et al. (2009) NFATc1 mediates Toll-like receptor-independent innate immune responses during Trypanosoma cruzi infection. PLoS Pathogens 5, e1000514
58Santiago, H.C. et al. (2005) Mice deficient in LRG-47 display enhanced susceptibility to Trypanosoma cruzi infection associated with defective hemopoiesis and intracellular control of parasite growth. Journal of Immunology 175, 8165-8172
59Silva, G.K. et al. Cutting edge: Nucleotide-binding oligomerization domain 1-dependent responses account for murine resistance against Trypanosoma cruzi infection. Journal of Immunology 184, 1148-1152
60Graefe, S.E. et al. (2003) Interleukin-12 but not interleukin-18 is required for immunity to Trypanosoma cruzi in mice. Microbes and Infection 5, 833-839
61Koga, R. et al. (2006) TLR-dependent induction of IFN-beta mediates host defense against Trypanosoma cruzi. Journal of Immunology 177, 7059-7066
62Ramasawmy, R. et al. (2009) Heterozygosity for the S180L variant of MAL/TIRAP, a gene expressing an adaptor protein in the Toll-like receptor pathway, is associated with lower risk of developing chronic Chagas cardiomyopathy. Journal of Infectious Diseases 199, 1838-1845
63Tabeta, K. et al. (2006) The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9. Nature Immunology 7, 156-164
64Kim, Y.M. et al. (2008) UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes. Nature 452, 234-238
65Biron, C.A. and Gazzinelli, R.T. (1995) Effects of IL-12 on immune responses to microbial infections: a key mediator in regulating disease outcome. Current Opinion in Immunology 7, 485-496
66Akira, S., Takeda, K. and Kaisho, T. (2001) Toll-like receptors: critical proteins linking innate and acquired immunity. Nature Immunology 2, 675-680
67Tardieux, I. et al. (1992) Lysosome recruitment and fusion are early events required for trypanosome invasion of mammalian cells. Cell 71, 1117-1130
68Andrade, L.O. and Andrews, N.W. (2005) The Trypanosoma cruzi-host-cell interplay: location, invasion, retention. Nature Reviews Microbiology 3, 819-823
69Burleigh, B.A. (2005) Host cell signaling and Trypanosoma cruzi invasion: do all roads lead to lysosomes? Science's STKE 2005, pe36
70Tardieux, I., Nathanson, M.H. and Andrews, N.W. (1994) Role in host cell invasion of Trypanosoma cruzi-induced cytosolic-free Ca2+ transients. Journal of Experimental Medicine 179, 1017-1022
71Chakrabarti, S., Andrade, L.O. and Andrews, N.W. (2005) Trypanosoma cruzi invades synaptotagmin VII-deficient cells by a PI-3 kinase independent pathway. Molecular and Biochemical Parasitology 141, 125-128
72Rodriguez, A. et al. (1995) A trypanosome-soluble factor induces IP3 formation, intracellular Ca2+ mobilization and microfilament rearrangement in host cells. Journal of Cell Biology 129, 1263-1273
73Woolsey, A.M. et al. (2003) Novel PI 3-kinase-dependent mechanisms of trypanosome invasion and vacuole maturation. Journal of Cell Science 116, 3611-3622
74Woolsey, A.M. and Burleigh, B.A. (2004) Host cell actin polymerization is required for cellular retention of Trypanosoma cruzi and early association with endosomal/lysosomal compartments. Cellular Microbiology 6, 829-838
75Andrade, L.O. and Andrews, N.W. (2004) Lysosomal fusion is essential for the retention of Trypanosoma cruzi inside host cells. Journal of Experimental Medicine 200, 1135-1143
76Tarleton, R.L. (1990) Depletion of CD8+ T cells increases susceptibility and reverses vaccine-induced immunity in mice infected with Trypanosoma cruzi. Journal of Immunology 144, 717-724
77Tarleton, R.L. et al. (1992) Susceptibility of beta 2-microglobulin-deficient mice to Trypanosoma cruzi infection. Nature 356, 338-340
78de Alencar, B.C. et al. (2009) Perforin and gamma interferon expression are required for CD4+ and CD8+ T-cell-dependent protective immunity against a human parasite, Trypanosoma cruzi, elicited by heterologous plasmid DNA prime-recombinant adenovirus 5 boost vaccination. Infection and Immunity 77, 4383-4395
79Tzelepis, F. et al. (2008) Infection with Trypanosoma cruzi restricts the repertoire of parasite-specific CD8+ T cells leading to immunodominance. Journal of Immunology 180, 1737-1748
80Rodrigues, M.M. et al. (2009) Immunodominance: a new hypothesis to explain parasite escape and host/parasite equilibrium leading to the chronic phase of Chagas' disease? Brazilian Journal of Medical and Biological Research 42, 220-223
81Tzelepis, F. et al. (2006) Distinct kinetics of effector CD8+ cytotoxic T cells after infection with Trypanosoma cruzi in naive or vaccinated mice. Infection and Immunity 74, 2477-2481
82Martin, D.L. et al. (2006) CD8+ T-cell responses to Trypanosoma cruzi are highly focused on strain-variant trans-sialidase epitopes. PLoS Pathogens 2, e77
83Haolla, F.A. et al. (2009) Strain-specific protective immunity following vaccination against experimental Trypanosoma cruzi infection. Vaccine 27, 5644-5653
84Coelho, P.S. et al. (2002) Glycosylphosphatidylinositol-anchored mucin-like glycoproteins isolated from Trypanosoma cruzi trypomastigotes induce in vivo leukocyte recruitment dependent on MCP-1 production by IFN-gamma-primed-macrophages. Journal of Leukocyte Biology 71, 837-844
85Petersen, C.A. and Burleigh, B.A. (2003) Role for interleukin-1 beta in Trypanosoma cruzi-induced cardiomyocyte hypertrophy. Infection and Immunity 71, 4441-4447
86Hall, B.S. et al. (2000) Cell-specific activation of nuclear factor-kappaB by the parasite Trypanosoma cruzi promotes resistance to intracellular infection. Molecular and Cell Biology 11, 153-160
87Huang, H. et al. (1999) Infection of endothelial cells with Trypanosoma cruzi activates NF-kappaB and induces vascular adhesion molecule expression. Infection and Immunity 67, 5434-5440
88Huang, H. et al. (2003) Activation of transcription factors AP-1 and NF-kappa B in murine Chagasic myocarditis. Infection and Immunity 71, 2859-2867
89Ropert, C. et al. (2001) Requirement of mitogen-activated protein kinases and I kappa B phosphorylation for induction of proinflammatory cytokines synthesis by macrophages indicates functional similarity of receptors triggered by glycosylphosphatidylinositol anchors from parasitic protozoa and bacterial lipopolysaccharide. Journal of Immunology 166, 3423-3431
90Machado, F.S. et al. (2000) Trypanosoma cruzi-infected cardiomyocytes produce chemokines and cytokines that trigger potent nitric oxide-dependent trypanocidal activity. Circulation 102, 3003-3008
91Burleigh, B.A. and Woolsey, A.M. (2002) Cell signalling and Trypanosoma cruzi invasion. Cellular Microbiology 4, 701-711
92Scharfstein, J. et al. (2000) Host cell invasion by Trypanosoma cruzi is potentiated by activation of bradykinin B(2) receptors. Journal of Experimental Medicine 192, 1289-1300
93Michailowsky, V. et al. (2004) Intercellular adhesion molecule 1 deficiency leads to impaired recruitment of T lymphocytes and enhanced host susceptibility to infection with Trypanosoma cruzi. Journal of Immunology 173, 463-470
94Talvani, A. et al. (2000) Kinetics of cytokine gene expression in experimental chagasic cardiomyopathy: tissue parasitism and endogenous IFN-gamma as important determinants of chemokine mRNA expression during infection with Trypanosoma cruzi. Microbes and Infection 2, 851-866
95dos Santos, P.V. et al. (2001) Prevalence of CD8(+)alpha beta T cells in Trypanosoma cruzi-elicited myocarditis is associated with acquisition of CD62L(Low)LFA-1(High)VLA-4(High) activation phenotype and expression of IFN-gamma-inducible adhesion and chemoattractant molecules. Microbes and Infection 3, 971-984
96Michailowsky, V. et al. (2001) Pivotal role of interleukin-12 and interferon-gamma axis in controlling tissue parasitism and inflammation in the heart and central nervous system during Trypanosoma cruzi infection. American Journal of Pathology 159, 1723-1733
97Aliberti, J.C. et al. (1996) Interleukin-12 mediates resistance to Trypanosoma cruzi in mice and is produced by murine macrophages in response to live trypomastigotes. Infection and Immunity 64, 1961-1967
98Marino, A.P. et al. (2004) Regulated on activation, normal T cell expressed and secreted (RANTES) antagonist (Met-RANTES) controls the early phase of Trypanosoma cruzi-elicited myocarditis. Circulation 110, 1443-1449
99Medeiros, G.A. et al. (2009) Treatment of chronically Trypanosoma cruzi-infected mice with a CCR1/CCR5 antagonist (Met-RANTES) results in amelioration of cardiac tissue damage. Microbes and Infection 11, 264-273
100Camargo, M.M. et al. (1997) Glycosylphosphatidylinositol-anchored mucin-like glycoproteins isolated from Trypanosoma cruzi trypomastigotes initiate the synthesis of proinflammatory cytokines by macrophages. Journal of Immunology 158, 5890-5901
101Souza, P.E. et al. (2007) Trypanosoma cruzi infection induces differential modulation of costimulatory molecules and cytokines by monocytes and T cells from patients with indeterminate and cardiac Chagas' disease. Infection and Immunity 75, 1886-1894
102Cunha-Neto, E. et al. (2009) Immunological and non-immunological effects of cytokines and chemokines in the pathogenesis of chronic Chagas disease cardiomyopathy. Memórias do Instituto Oswaldo Cruz 1, 252-258
103Calzada, J.E. et al. (2001) Chemokine receptor CCR5 polymorphisms and Chagas' disease cardiomyopathy. Tissue Antigens 58, 154-158
104Calzada, J.E. et al. (2009) Transforming growth factor beta 1 (TGFbeta1) gene polymorphisms and Chagas disease susceptibility in Peruvian and Colombian patients. Cytokine 45, 149-153
105Costa, G.C. et al. (2009) Functional IL-10 gene polymorphism is associated with Chagas disease cardiomyopathy. Journal of Infectious Diseases 199, 451-454
106Drigo, S.A. et al. (2006) TNF gene polymorphisms are associated with reduced survival in severe Chagas' disease cardiomyopathy patients. Microbes and Infection 8, 598-603
107Filardi, L.S. and Brener, Z. (1987) Susceptibility and natural resistance of Trypanosoma cruzi strains to drugs used clinically in Chagas disease. Transactions of the Royal Society of Tropical Medicine and Hygiene 81, 755-759
108Murta, S.M. et al. (1998) Molecular characterization of susceptible and naturally resistant strains of Trypanosoma cruzi to benznidazole and nifurtimox. Molecular and Biochemical Parasitology 93, 203-214
109Veloso, V.M. et al. (2001) Variation in susceptibility to benznidazole in isolates derived from Trypanosoma cruzi parental strains. Memórias do Instituto Oswaldo Cruz 96, 1005-1011
110Galvao, L.M. et al. (1993) Lytic antibody titre as a means of assessing cure after treatment of Chagas disease: a 10 years follow-up study. Transactions of the Royal Society of Tropical Medicine and Hygiene 87, 220-223
111Krettli, A.U., Cancado, J.R. and Brener, Z. (1982) Effect of specific chemotherapy on the levels of lytic antibodies in Chagas's disease. Transactions of the Royal Society of Tropical Medicine and Hygiene 76, 334-340
112Murta, S.M. et al. (1999) In-vivo treatment with benznidazole enhances phagocytosis, parasite destruction and cytokine release by macrophages during infection with a drug-susceptible but not with a derived drug-resistant Trypansoma cruzi population. Parasite Immunology 21, 535-544
113Sathler-Avelar, R. et al. (2006) Benznidazole treatment during early-indeterminate Chagas' disease shifted the cytokine expression by innate and adaptive immunity cells toward a type 1-modulated immune profile. Scandinavian Journal of Immunology 64, 554-563
114Romanha, A.J. et al. (2002) Experimental chemotherapy against Trypanosoma cruzi infection: essential role of endogenous interferon-gamma in mediating parasitologic cure. Journal of Infectious Diseases 186, 823-828
115Michailowsky, V. et al. (1998) Interleukin-12 enhances in vivo parasiticidal effect of benznidazole during acute experimental infection with a naturally drug-resistant strain of Trypanosoma cruzi. Antimicrobial Agents and Chemotherapy 42, 2549-2556
116Ferraz, M.L. et al. (2007) The anti-Trypanosoma cruzi activity of posaconazole in a murine model of acute Chagas' disease is less dependent on gamma interferon than that of benznidazole. Antimicrobial Agents and Chemotherapy 51, 1359-1364
117Ferraz, M.L. et al. (2009) Absence of CD4+ T lymphocytes, CD8+ T lymphocytes, or B lymphocytes has different effects on the efficacy of posaconazole and benznidazole in treatment of experimental acute Trypanosoma cruzi infection. Antimicrobial Agents and Chemotherapy 53, 174-179
118Rodrigues, M.M. et al. (2009) Swimming against the current: genetic vaccination against Trypanosoma cruzi infection in mice. Memórias do Instituto Oswaldo Cruz 1, 281-287
119Vollmer, J. and Krieg, A.M. (2009) Immunotherapeutic applications of CpG oligodeoxynucleotide TLR9 agonists. Advanced Drug Delivery Reviews 61, 195-204
120Tagliabue, A. and Rappuoli, R. (2008) Vaccine adjuvants: the dream becomes real. Human Vaccines 4, 347-349
121Moyle, P.M. and Toth, I. (2008) Self-adjuvanting lipopeptide vaccines. Current Medicinal Chemistry 15, 506-516
122Araujo, A.F. et al. (2005) CD8+-T-cell-dependent control of Trypanosoma cruzi infection in a highly susceptible mouse strain after immunization with recombinant proteins based on amastigote surface protein 2. Infection and Immunity 73, 6017-6025
123Machado, A.V. et al. (2006) Long-term protective immunity induced against Trypanosoma cruzi infection after vaccination with recombinant adenoviruses encoding amastigote surface protein-2 and trans-sialidase. Human Gene Therapy 17, 898-908
124Vasconcelos, J.R. et al. (2004) Protective immunity against trypanosoma cruzi infection in a highly susceptible mouse strain after vaccination with genes encoding the amastigote surface protein-2 and trans-sialidase. Human Gene Therapy 15, 878-886
125Hoft, D.F. et al. (2007) Trans-sialidase recombinant protein mixed with CpG motif-containing oligodeoxynucleotide induces protective mucosal and systemic trypanosoma cruzi immunity involving CD8+ CTL and B cell-mediated cross-priming. Journal of Immunology 179, 6889-6900
126Zapata-Estrella, H. et al. (2006) Control of Trypanosoma cruzi infection and changes in T-cell populations induced by a therapeutic DNA vaccine in mice. Immunology Letters 103, 186-191
127Sanchez-Burgos, G. et al. (2007) Comparative evaluation of therapeutic DNA vaccines against Trypanosoma cruzi in mice. FEMS Immunology and Medical Microbiology 50, 333-341
128Dunn, G.P., Old, L.J. and Schreiber, R.D. (2004) The immunobiology of cancer immunosurveillance and immunoediting. Immunity 21, 137-148
129Vaidian, A.K., Weiss, L.M. and Tanowitz, H.B. (2004) Chagas' disease and AIDS. Biology and Disease 3, 2
130Krementsov, N. (2009) Trypanosoma cruzi, cancer and the Cold War. História, Ciências, Saúde-Manguinhos 1, 75-94
131Roskin, G. and Exempliarskaia, E. (1931) Protozoeninfektion und experimenteller Krebs. Zeitschrift fur Krebsforschung 34, 628-645
132Roskin, G. and Romanova, K. (1938) Traitment du cancer experimental par les endotoxins des protozoaries. Archives Internationales de Médécine Experimentale 13, 379-384
133Roskin, G. and Romanova, K. (1935) Action des toxines sur le cancer experimental. Acta Cancrologica 1, 323-234
134Bongard, P. and Roskin, G. (1939) Deistvie shizotripannogo endotoksina na zlokachestvenye opukholi. Biulleten' Eksperimental'noi Biologii i Meditsiny 7, 411-412, 417-418
135Malisoff, W.M. (1947) The action of the endotoxin of trypanosoma cruzi (KR) on malignant mouse tumors. Science 106, 591-594
136Hauschka, T.S. and Goodwin, M.B. (1948) Trypanosoma cruzi endotoxin (KR) in the treatment of malignant mouse tumors. Science 107, 600-602
137Meyer, H. and Chagas, C. (1950) Cultivation of S. cruzi in tissues cultures of the spindle cell sarcoma ‘Roffo’. Anais da Academia Brasileira de Ciências 22, 175-182
138Galliard, H., Brumpt, C. and Martines, R. (1950) Infections experimentales a T. cruzi a propos de la biotherapie du cancer. Bulletin de la Société de Pathologie Exotique 43, 204-216
139Belkin, M. (1949) Absence of effect of lysed T. cruzi preparations on sarcoma 37. Cancer Research 9, 560
140Lima, M.T. et al. (1991) Trypanosoma cruzi: properties of a clone isolated from CL strain. Parasitology Research 77, 77-81
141Lima, M.T., Lenzi, H.L. and Gattass, C.R. (1995) Negative tissue parasitism in mice injected with a noninfective clone of Trypanosoma cruzi. Parasitology Research 81, 6-12
142Pyrrho, A.S. et al. (1998) Trypanosoma cruzi: IgG1 and IgG2b are the main immunoglobulins produced by vaccinated mice. Parasitology Research 84, 333-337
143Paiva, C.N. et al. (1999) Trypanosoma cruzi: protective response of vaccinated mice is mediated by CD8+ cells, prevents signs of polyclonal T lymphocyte activation, and allows restoration of a resting immune state after challenge. Experimental Parasitology 91, 7-19
144Paiva, C.N. et al. (1999) Trypanosoma cruzi: lack of T cell abnormalities in mice vaccinated with live trypomastigotes. Parasitology Research 85, 1012-1017
145Chen, Y.T. et al. (1997) Genomic cloning and localization of CTAG, a gene encoding an autoimmunogenic cancer-testis antigen NY-ESO-1, to human chromosome Xq28. Cytogenetics and Cell Genetics 79, 237-240
146Gnjatic, S. et al. (2006) NY-ESO-1: review of an immunogenic tumor antigen. Advances in Cancer Research 95, 1-30
Gazzinelli, R.T. and Denkers, E.Y. (2006) Protozoan encounters with Toll-like receptor signalling pathways: implications for host parasitism. Nature Reviews Immunology 6, 895-906
Takeuchi, O. and Akira, S. (2010) Pattern recognition receptors and inflammation. Cell 140, 805-820
Padilla, A.M., Bustamante, J.M. and Tarleton, R.L. (2009) CD8+ T cells in Trypanosoma cruzi infection. Current Opinion in Immunology 21, 385-390
Rodrigues, M.M. et al. (2009) Immunodominance: a new hypothesis to explain parasite escape and host/parasite equilibrium leading to the chronic phase of Chagas' disease? Brazilian Journal of Medical and Biological Research 42, 220-223
Rassi, A. Jr, Rassi, A and Marin-Neto, J.A. (2010) Chagas disease. Lancet 375, 1388-1402
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Expert Reviews in Molecular Medicine
  • ISSN: -
  • EISSN: 1462-3994
  • URL: /core/journals/expert-reviews-in-molecular-medicine
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