Immune Evasion Strategies of Trypanosoma cruzi

Journal of Immunology Research

Volumn 2015, Issue , 2015, Pages

  Flávia Nardy, Ana ^a   Freire De Lima, Célio Geraldo ^a   Morrot, Alexandre ^a  

^a FEDERAL UNIVERSITY OF RIO DE JANEIRO   (Brazil)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; MUCIN; SIALIC ACID BINDING IMMUNOGLOBULIN LIKE LECTIN; VIRULENCE FACTOR;

ADAPTIVE IMMUNITY; CHAGAS DISEASE; DENDRITIC CELL; HOST RESISTANCE; IMMUNE EVASION; INNATE IMMUNITY; NONHUMAN; REVIEW; SIALYLATION; THYMUS; TRYPANOSOMA CRUZI; DISEASE RESISTANCE; HOST PARASITE INTERACTION; HUMAN; IMMUNOLOGICAL TOLERANCE; IMMUNOLOGY; METABOLISM; PARASITOLOGY; PATHOGENICITY; T LYMPHOCYTE SUBPOPULATION;

CHAGAS DISEASE; DISEASE RESISTANCE; HOST-PARASITE INTERACTIONS; HUMANS; IMMUNE EVASION; IMMUNE TOLERANCE; T-LYMPHOCYTE SUBSETS; TRYPANOSOMA CRUZI; VIRULENCE FACTORS;

EID: 84937716039     PISSN: 23148861     EISSN: 23147156     Source Type: Journal    
DOI: 10.1155/2015/178947     Document Type: Review

References (99)

1. A. L. Ribeiro, M. P. Nunes, M. M. Teixeira, and M. O. Rocha, "Diagnosis and management of Chagas disease and cardiomyopathy, " Nature Reviews Cardiology, vol. 9, no. 10, pp. 576-589, 2012.
2. M. A. Barry, J. E. Weatherhead, P. J. Hotez, and L. Woc-Colburn, "Childhood parasitic infections endemic to the United States, " Pediatric Clinics of North America, vol. 60, no. 2, pp. 471-485, 2013.
3. A. Prata, "Clinical and epidemiological aspects of chagas disease, " The Lancet Infectious Diseases, vol. 1, no. 2, pp. 92-100, 2001.
4. N. Gironès, H. Cuervo, and M. Fresno, "Trypanosoma cruziinduced molecular mimicry and Chagas' disease, " Current Topics in Microbiology and Immunology, vol. 296, pp. 89-123, 2005.
5. F. R. S. Gutierrez, P. M. M. Guedes, R. T. Gazzinelli, and J. S. Silva, "The role of parasite persistence in pathogenesis ofChagas heart disease, " Parasite Immunology, vol. 31, no. 11, pp. 673-685, 2009.
6. E. Cunha-Neto, P. C. Teixeira, L. G. Nogueira, and J. Kalil, "Autoimmunity, " Advances in Parasitology, vol. 76, pp. 129-152, 2011.
7. E. S. Garcia, F. A. Genta, P. de Azambuja, and G. A. Schaub, "Interactions between intestinal compounds of triatomines and Trypanosoma cruzi, " Trends in Parasitology, vol. 26, no. 10, pp. 499-505, 2010.
8. H. B. Tanowitz, J. P. Gumprecht, D. Spurr et al., "Cytokine gene expression of endothelial cells infected with Trypanosoma cruzi, " Journal of Infectious Diseases, vol. 166, no. 3, pp. 598-603, 1992.
9. H. Huang, T. M. Calderon, J. W. Berman et al., "Infection of endothelial cells with Trypanosoma cruzi activates NF-B and induces vascular adhesion molecule expression, " Infection and Immunity, vol. 67, no. 10, pp. 5434-5440, 1999.
10. B. Chandrasekar, P. C. Melby, D. A. Troyer, and G. L. Freeman, "Differential regulation of nitric oxide synthase isoforms in experimental acute Chagasic cardiomyopathy, " Clinical and Experimental Immunology, vol. 121, no. 1, pp. 112-119, 2000.
11. M. M. Teixeira, R. T. Gazzinelli, and J. S. Silva, "Chemokines, inflammation and Trypanosoma cruzi infection, " Trends in Parasitology, vol. 18, no. 6, pp. 262-265, 2002.
12. S. Mukherjee, H. Huang, S. B. Petkova et al., "Trypanosoma cruizi infection activates extracellular signal-regulated kinase in cultured endothelial and smooth muscle cells, " Infection and Immunity, vol. 72, no. 9, pp. 5274-5282, 2004.
13. K. M. Tyler, C. L. Olson, and D. M. Engman, "The life cycle of Trypanosoma cruzi, " in American Trypanosomiasis, vol. 7 of World Class Parasites, pp. 1-11, Springer, 2003.
14. L. M. de Pablos and A. Osuna, "Multigene families in Trypanosoma cruzi and their role in infectivity, " Infection and Immunity, vol. 80, no. 7, pp. 2258-2264, 2012.
15. K. A. Norris, B. Bradt, N. R. Cooper, and S. O. Magdalene, "Characterization of a Trypanosoma cruzi C3 binding protein with functional and genetic similarities to the human complement regulatory protein, decay-accelerating factor, " The Journal of Immunology, vol. 147, no. 7, pp. 2240-2247, 1991.
16. S. Zambrano-Villa, D. Rosales-Borjas, J. C. Carrero, and L. Ortiz-Ortiz, "How protozoan parasites evade the immune response, " Trends in Parasitology, vol. 18, no. 6, pp. 272-278, 2002.
17. D. M. Paulnock and S. P. Coller, "Analysis of macrophage activation in African trypanosomiasis, " Journal of Leukocyte Biology, vol. 69, no. 5, pp. 685-690, 2001.
18. M. Desjardins and A. Descoteaux, "Inhibition of phagolysosomal biogenesis by the Leishmania lipophosphoglycan, " Journal of Experimental Medicine, vol. 185, no. 12, pp. 2061-2068, 1997.
19. A. L. Sorensen, A. S. Hey, and A. Kharazmi, "Leishmania major surface protease Gp63 interferes with the function of human monocytes and neutrophils in vitro, " Acta Pathologica, Microbiologica et Immunologica Scandinavica, vol. 102, no. 4, pp. 265-271, 1994.
20. C. Bogdan and M. Röllinghoff, "How do protozoan parasites survive inside macrophages?" Parasitology Today, vol. 15, no. 1, pp. 22-28, 1999.
21. J. de Diego, C. Punzón, M. Duarte, and M. Fresno, "Alteration of macrophage function by a Trypanosoma cruzi membrane mucin, " The Journal of Immunology, vol. 159, no. 10, pp. 4983-4989, 1997.
22. P. S. Doyle, Y. M. Zhou, I. Hsieh, D. C. Greenbaum, J. H. McKerrow, and J. C. Engel, "The trypanosoma cruzi protease cruzain mediates immune evasion, " PLoS Pathogens, vol. 7, no. 9, Article ID e1002139, 2011.
23. C. A. Hunter, L. A. Ellis-Neyes, T. Slifer et al., "IL-10 is required to prevent immune hyperactivity during infection with Trypanosoma cruzi, " Journal of Immunology, vol. 158, no. 7, pp. 3311-3316, 1997.
24. J. S. Silva, D. R. Twardzik, and S. G. Reed, "Regulation of Trypanosoma cruzi infections in vitro and in vivo by transforming growth factor β (TGF-β), "The Journal of Experimental Medicine, vol. 174, no. 3, pp. 539-545, 1991.
25. L. Lauria-Pires and A. R. L. Teixeira, "Virulence and pathogenicity associated with diversity of Trypanosoma cruzi stocks and clones derived from Chagas' disease patients, " The American Journal of Tropical Medicine and Hygiene, vol. 55, no. 3, pp. 304-310, 1996.
26. M. R. S. Briones, R. P. Souto, B. S. Stolf, and B. Zingales, "The evolution of two Trypanosoma cruzi subgroups inferred from rRNAgenes can be correlated with the interchange of American mammalian faunas in the Cenozoic and has implications to pathogenicity and host specificity, " Molecular and Biochemical Parasitology, vol. 104, no. 2, pp. 219-232, 1999.
27. F. Noireau, P. Diosque, and A. M. Jansen, "Trypanosoma cruzi: adaptation to its vectors and its hosts, " Veterinary Research, vol. 40, no. 2, article 26, pp. 1-23, 2009.
28. D. L. Martin, D. B. Weatherly, S. A. Laucella et al., "CD8+ T-Cell responses to Trypanosoma cruzi are highly focused on strainvariant trans-sialidase epitopes, " PLoS Pathogens, vol. 2, no. 8, article e77, 2006.
29. G. A. DosReis, C. G. Freire-De-Lima, M. P. Nunes, and M. F. Lopes, "The importance of aberrant T-cell responses in Chagas disease, " Trends in Parasitology, vol. 21, no. 5, pp. 237-243, 2005.
30. F. Nagajyothi, F. S. Machado, B. A. Burleigh et al., "Mechanisms of Trypanosoma cruzi persistence in Chagas disease, " Cellular Microbiology, vol. 14, no. 5, pp. 634-643, 2012.
31. A. Oladiran and M. Belosevic, "Immune evasion strategies of trypanosomes: a review, " Journal of Parasitology, vol. 98, no. 2, pp. 284-292, 2012.
32. F. Y. Liew, M. T. Scott, D. S. Liu, and S. L. Croft, "Suppressive substance produced by T cells from mice chronically infected with Trypanosoma cruzi, I. Preferential inhibition of the induction of delayed-type hypersensitivity, " Journal of Immunology, vol. 139, no. 7, pp. 2452-2457, 1987.
33. F. Kierszenbaum, J. L. de Diego, M. Fresno, and M. B. Sztein, "Inhibitory effects of the Trypanosoma cruzi membrane glycoprotein AGC10 on the expression of IL-2 receptor chains and secretion of cytokines by subpopulations of activated human T lymphocytes, " European Journal of Immunology, vol. 29, no. 5, pp. 1684-1691, 1999.
34. F. Kierszenbaum, M. Fresno, and M. B. Sztein, "The Trypanosoma cruzimembrane glycoproteinAGC10 inhibits human lymphocyte activation by a mechanism preceding translation of both, interleukin-2 and its high-affinity receptor subunits, " Molecular and Biochemical Parasitology, vol. 125, no. 1-2, pp. 91-101, 2002.
35. L. vanOvertvelt, M. Andrieu, V. Verhasselt et al., "Trypanosoma cruzi down-regulates lipopolysaccharide-induced MHC class I on human dendritic cells and impairs antigen presentation to specific CD8+ T lymphocytes, " International Immunology, vol. 14, no. 10, pp. 1135-1144, 2002.
36. G. A. DosReis, "Evasion of immune responses by Trypanosoma cruzi, the etiological agent of Chagas disease, " Brazilian Journal ofMedical and Biological Research, vol. 44, no. 2, pp. 84-90, 2011.
37. P. Alcaide and M. Fresno, "The Trypanosoma cruzi membrane mucin AgC10 inhibits T cell activation and IL-2 transcription through L-selectin, " International Immunology, vol. 16, no. 10, pp. 1365-1375, 2004.
38. A. M. Padilla, L. J. Simpson, and R. L. Tarleton, "Insufficient TLR activation contributes to the slow development of CD8+ T cell responses in Trypanosoma cruzi infection, " Journal of Immunology, vol. 183, no. 2, pp. 1245-1252, 2009.
39. M. J. Pinazo, G. Espinosa, C. Cortes-Lletget et al., "Immunosuppression and chagas disease: amanagement challenge, " PLoS Neglected Tropical Diseases, vol. 7, no. 1, Article ID e1965, 2013.
40. J. R. Maleckar and F. Kierszenbaum, "Inhibition of mitogeninduced proliferation of mouse T and B lymphocytes by bloodstream forms of Trypanosoma cruzi, " The Journal of Immunology, vol. 130, no. 2, pp. 908-911, 1983.
41. L. Ortiz-Ortiz, D. E. Parks, M. Rodriguez, and W. O. Weigle, "Polyclonal B lymphocyte activation during Trypanosoma cruzi infection, "The Journal of Immunology, vol. 124, no. 1, pp. 121-126, 1980.
42. I. A. Abrahamsohn and R. L. Coffman, "Cytokine and nitric oxide regulation of the immunosuppression in Trypanosoma cruzi infection, " Journal of Immunology, vol. 155, no. 8, pp. 3955-3963, 1995.
43. G. A. Martins, M. A. G. Cardoso, J. C. S. Aliberti, and J. S. Silva, "Nitric oxide-induced apoptotic cell death in the acute phase of Trypanosoma cruzi infection in mice, " Immunology Letters, vol. 63, no. 2, pp. 113-120, 1998.
44. M. P. Nunes, R. M. Andrade, M. F. Lopes, and G. A. DosReis, "Activation-induced T cell death exacerbates Trypanosoma cruzi replication in macrophages cocultured with CD4+ T lymphocytes from infected hosts, " Journal of Immunology, vol. 160, no. 3, pp. 1313-1319, 1998.
45. S. Schenkman, M.-S. Jiang, G. W. Hart, and V. Nussenzweig, "A novel cell surface trans-sialidase of Trypanosoma cruzi generates a stage-specific epitope required for invasion ofmammalian cells, " Cell, vol. 65, no. 7, pp. 1117-1125, 1991.
46. S. Schenkman, D. Eichinger, M. E. A. Pereira, and V. Nussenzweig, "Structural and functional properties of Trypanosoma trans-sialidase, " Annual Review of Microbiology, vol. 48, pp. 499-523, 1994.
47. J. O. Previato, C. Jones, M. T. Xavier et al., "Structural characterization of the major glycosylphosphatidylinositol membrane-anchored glycoprotein from epimastigote forms of Trypanosoma cruzi Y-strain, " The Journal of Biological Chemistry, vol. 270, no. 13, pp. 7241-7250, 1995.
48. M. Eugenia Giorgi and R. M. de Lederkremer, "Trans-sialidase and mucins of Trypanosoma cruzi: an important interplay for the parasite, " Carbohydrate Research, vol. 346, no. 12, pp. 1389-1393, 2011.
49. J. M. Di Noia, D. O. Sanchez, and A. C. C. Frasch, "The protozoan Trypanosoma cruzi has a family of genes resembling the mucin genes of mammalian cells, "The Journal of Biological Chemistry, vol. 270, no. 41, pp. 24146-24149, 1995.
50. C. A. Buscaglia, V. A. Campo, A. C. C. Frasch, and J. M. di Noia, "Trypanosoma cruzi surfacemucins: host-dependent coat diversity, " Nature reviews, Microbiology, vol. 4, no. 3, pp. 229-236, 2006.
51. L. Mendonça-Previato, L. Penha, T. C. Garcez, C. Jones, and J. O. Previato, "Addition of α-O-GlcNAc to threonine residues define the post-translational modification of mucin-like molecules in Trypanosoma cruzi, " Glycoconjugate Journal, vol. 30, no. 7, pp. 659-666, 2013.
52. K. Joiner, A. Sher, T. Gaither, and C. Hammer, "Evasion of alternative complement pathway by Trypanosoma cruzi results frominefficient binding of factor B, " Proceedings of the National Academy of Sciences of the United States of America, vol. 83, no. 17, pp. 6593-6597, 1986.
53. R. T. Gazzinelli, M. E. S. Pereira, A. Romanha, G. Gazzinelli, and Z. Brener, "Direct lysis of Trypanosoma cruzi: a novel effector mechanism of protection mediated by human anti-gal antibodies, " Parasite Immunology, vol. 13, no. 4, pp. 345-356, 1991.
54. T. L. Kipnis, J. R. David, C. A. Alper, A. Sher, and W. D. da Silva, "Enzymatic treatment transforms trypomastigotes of Trypanosoma cruzi into activators of alternative complement pathway and potentiates their uptake by macrophages, " Proceedings of the National Academy of Sciences of the United States of America, vol. 78, no. 1, pp. 602-605, 1981.
55. V. L. Pereira-Chioccola, A. Acosta-Serrano, I. C. De Almeida et al., "Mucin-like molecules form a negatively charged coat that protects Trypanosoma cruzi trypomastigotes from killing by human anti-α-galactosyl antibodies, " Journal of Cell Science, vol. 113, no. 7, pp. 1299-1307, 2000.
56. H. Erdmann, C. Steeg, F. Koch-Nolte, B. Fleischer, and T. Jacobs, "Sialylated ligands on pathogenic Trypanosoma cruzi interact with Siglec-E (sialic acid-binding Ig-like lectin-E), " Cellular Microbiology, vol. 11, no. 11, pp. 1600-1611, 2009.
57. M. P. Nunes, B. Fortes, J. L. Silva-Filho et al., "Inhibitory effects of Trypanosoma cruzi sialoglycoproteins on C D4+ T Cells are associated with increased susceptibility to infection, " PLoS ONE, vol. 8, no. 10, Article IDe77568, 2013.
58. H. Erdmann, C. Steeg, F. Koch-Nolte, B. Fleischer, and T. Jacobs, "Sialylated ligands on pathogenic Trypanosoma cruzi interact with Siglec-E (sialic acid-binding Ig-like lectin-E), " Cellular Microbiology, vol. 11, no. 11, pp. 1600-1611, 2009.
59. T. Jacobs, H. Erdmann, and B. Fleischer, "Molecular interaction of Siglecs (sialic acid-binding Ig-like lectins) with sialylated ligands on Trypanosoma cruzi, "EuropeanJournal of Cell Biology, vol. 89, no. 1, pp. 113-116, 2010.
60. A. Ouaissi, A. C. da Silva, A. G. Guevara, M. Borges, and E. Guilvard, "Trypanosoma cruzi-induced host immune system dysfunction: a rationale for parasite immunosuppressive factor( s) encoding gene targeting, " Journal of Biomedicine and Biotechnology, vol. 1, no. 1, pp. 11-17, 2001.
61. A. M. Acosta and C. A. Santos-Buch, "Autoimmunemyocarditis induced by Trypanosoma cruzi, " Circulation, vol. 71, no. 6, pp. 1255-1261, 1985.
62. F. Kierszenbaum, "Chagas' disease and the autoimmunity hypothesis, " Clinical Microbiology Reviews, vol. 12, no. 2, pp. 210-223, 1999.
63. D. M. Engman and J. S. Leon, "Pathogenesis of Chagas heart disease: role of autoimmunity, " Acta Tropica, vol. 81, no. 2, pp. 123-132, 2002.
64. L. Klein, M. Hinterberger, G. Wirnsberger, and B. Kyewski, "Antigen presentation in the thymus for positive selection and central tolerance induction, " Nature Reviews Immunology, vol. 9, no. 12, pp. 833-844, 2009.
65. A. Basten and P. A. Silveira, "B-cell tolerance: mechanisms and implications, " CurrentOpinion in Immunology, vol. 22, no. 5, pp. 566-574, 2010.
66. K. Pieper, B. Grimbacher, and H. Eibel, "B-cell biology and development, " Journal of Allergy and Clinical Immunology, vol. 131, no. 4, pp. 959-971, 2013.
67. A. A. Freitas and B. Rocha, "Population biology of lymphocytes: the flight for survival, " Annual Review of Immunology, vol. 18, pp. 83-111, 2000.
68. C. Montaudouin, M. Anson, Y. Hao et al., "Quorum sensing contributes to activated IgM-secreting B cell homeostasis, " The Journal of Immunology, vol. 190, no. 1, pp. 106-114, 2013.
69. C. A. M. Bento, M. B. Melo, J. O. Previato, L. Mendonça-Previato, and L. M. T. Peçanha, "Glycoinositolphospholipids purified from Trypanosoma cruzi stimulate Ig production in vitro, "The Journal of Immunology, vol. 157, no. 11, pp. 4996-5001, 1996.
70. J. O. Previato, R. Wait, C. Jones et al., "Glycoinositolphospholipid from Trypanosoma cruzi: structure, biosynthesis and immunobiology, " Advances in Parasitology, vol. 56, pp. 1-41, 2003.
71. A.-C. Oliveira, J. R. Peixoto, L. B. De Arrada et al., "Expression of functional TLR4 confers proinflammatory responsiveness to Trypanosoma cruzi glycoinositolphospholipids and higher resistance to infection with T. cruzi, " Journal of Immunology, vol. 173, no. 9, pp. 5688-5696, 2004.
72. B. Reina-San-Martín, W. Degrave, C. Rougeot et al., "A B-cell mitogen froma pathogenic trypanosome is a eukaryotic proline racemase, " Nature Medicine, vol. 6, no. 8, pp. 890-897, 2000.
73. N. Chamond, C. Grégoire, N. Coatnoan et al., "Biochemical characterization of proline racemases from the human protozoan parasite Trypanosoma cruzi and definition of putative protein signatures, "The Journal of Biological Chemistry, vol. 278, no. 18, pp. 15484-15494, 2003.
74. F. S. Dhabhar, "A hassle a day may keep the pathogens away: the fight-or-flight stress response and the augmentation of immune function, " Integrative and Comparative Biology, vol. 49, no. 3, pp. 215-236, 2009.
75. E. Calcagni and I. Elenkov, "Stress system activity, innate and T helper cytokines, and susceptibility to immune-related diseases, " Annals of the New York Academy of Sciences, vol. 1069, pp. 62-76, 2006.
76. E. Roggero, A. R. Pérez, M. Tamae-Kakazu et al., "Edogenous glucocorticoids cause thymus atrophy but are protective during acute Trypanosoma cruzi infection, " Journal of Endocrinology, vol. 190, no. 2, pp. 495-503, 2006.
77. A. R. Pérez, L. R. Berbert, A. Lepletier et al., "TNF-α is involved in the abnormal thymocyte migration during experimental Trypanosoma cruzi infection and favors the export of immature cells, " PLoS ONE, vol. 7, no. 3, Article ID e34360, 2012.
78. W. Savino and M. Dardenne, "Neuroendocrine control of thymus physiology, " Endocrine Reviews, vol. 21, no. 4, pp. 412-443, 2000.
79. W. Savino, "The thymus is a common target organ in infectious diseases, " PLoS Pathogens, vol. 2, no. 6, article e62, 2006.
80. W. Savino, M. Dardenne, C. Marche et al., "Thymic epithelium in AIDS, An immunohistologic study, " The American Journal of Pathology, vol. 122, no. 2, pp. 302-307, 1986.
81. H. Suzuki, M. Motohara, A. Miyake et al., "Intrathymic effect of acute pathogenic SHIV infection on T-lineage cells in newborn macaques, " Microbiology and Immunology, vol. 49, no. 7, pp. 667-679, 2005.
82. C. Godfraind, K. V. Holmes, and J.-P. Coutelier, "Thymus involution induced by mouse hepatitis virus A59 in BALB/c mice, " Journal of Virology, vol. 69, no. 10, pp. 6541-6547, 1995.
83. W. Chen, R. Kuolee, J. W. Austin, H. Shen, Y. Che, and J. W. Conlan, "Low dose aerosol infection of mice with virulent type A Francisella tularensis induces severe thymus atrophy and CD4+CD8+ thymocyte depletion, " Microbial Pathogenesis, vol. 39, no. 5-6, pp. 189-196, 2005.
84. S. R. Watson, T. J. Redington, T. B. Miller, and W, E. Bullock, "Flowmicrofluorometry analysis of alterations in T-lymphocyte subsets during murine listeriosis, " Infection and Immunity, vol. 45, no. 2, pp. 372-377, 1984.
85. M. C. Leite de Moraes, M. Hontebeyrie-Joskowicz, F. Leboulenger, W. Savino, M. Dardenne, and F. Lepault, "Studies on the thymus in Chagas' disease, II. Thymocyte subset fluctuations in Trypanosoma cruzi-infected mice: relationship to stress, " Scandinavian Journal of Immunology, vol. 33, no. 3, pp. 267-275, 1991.
86. E. Seixas and D. Ostler, "Plasmodium chabaudi chabaudi (AS): differential cellular responses to infection in resistant and susceptible mice, " Experimental Parasitology, vol. 110, no. 4, pp. 394-405, 2005.
87. V. N. Brito, P. C. S. Souto, M. A. Cruz-Höfling, L. C. Ricci, and L. Verinaud, "Thymus invasion and atrophy induced by Paracoccidioides brasiliensis in BALB/c mice, " Medical Mycology, vol. 41, no. 2, pp. 83-87, 2003.
88. S. R. Watson, T. B. Miller, T. J. Redington, and W, E. Bullock, "Immunoregulation in experimental disseminated histoplasmosis: flow microfluorometry (FMF) of the Thy and Lyt phenotypes of T lymphocytes from infected mice, " The Journal of Immunology, vol. 131, no. 2, pp. 984-990, 1983.
89. A. R. Pérez, E. Roggero, A. Nicora et al., "Thymus atrophy during Trypanosoma cruzi infection is caused by an immunoendocrine imbalance, " Brain, Behavior, and Immunity, vol. 21, no. 7, pp. 890-900, 2007.
90. D. A. Farias-de-Oliveira, D. M. S. Villa-Verde, P. H. N. Panzenhagen et al., "Caspase-8 and caspase-9 mediate thymocyte apoptosis in Trypanosoma cruzi acutely infected mice, " Journal of Leukocyte Biology, vol. 93, no. 2, pp. 227-234, 2013.
91. M. C. Leite-de-Moraes, M. Hontebeyrie-Joskowicz, M. Dardenne, and W. Savino, "Modulation of thymocyte subsets during acute and chronic phases of experimental Trypanosoma cruzi infection, " Immunology, vol. 77, no. 1, pp. 95-98, 1992.
92. J. deMeis, A. Morrot, D. A. Farias-de-Oliveira, D. M. S. Villa-Verde, and W. Savino, "Differential regional immune response in Chagas disease, " PLoS Neglected Tropical Diseases, vol. 3, no. 7, article e417, 2009.
93. A. Morrot, E. Terra-Granado, A. R. Pérez et al., "Chagasic thymic atrophy does not affect negative selection but results in the export of activated CD4+CD8+ T cells in severe forms of human disease, " PLoS Neglected Tropical Diseases, vol. 5, no. 8, Article ID e1268, 2011.
94. A. Lepletier, L. de Almeida, L. Santos et al., "Early doublenegative thymocyte export in Trypanosoma cruzi infection is restricted by sphingosine receptors and associated with human chagas disease, " PLoS Neglected Tropical Diseases, vol. 8, no. 10, Article ID e3203, 2014.
95. D. A. Mendes-da-Cruz, J. deMeis, V. Cotta-de-Almeida, and W. Savino, "Experimental Trypanosoma cruzi infection alters the shaping of the central and peripheralT-cell repertoire, " Microbes and Infection, vol. 5, no. 10, pp. 825-832, 2003.
96. W. Savino, M. Do Carmo Leite-de-Moraes, M. Hontebeyrie-Joskowicz, and M. Dardenne, "Studies on the thymus in Chagas' disease, I. Changes in the thymic microenvironment in mice acutely infected with Trypanosoma cruzi, " European Journal of Immunology, vol. 19, no. 9, pp. 1727-1733, 1989.
97. R. Pacholczyk and J. Kern, "The T-cell receptor repertoire of regulatory T cells, " Immunology, vol. 125, no. 4, pp. 450-458, 2008.
98. A. P. Jackson, "Genome evolution in trypanosomatid parasites, " Parasitology, pp. 1-17, 2014.
99. A. M. Macedo, C. R. Machado, R. P. Oliveira, and S. D. J. Pena, "Trypanosoma cruzi: genetic structure of populations and relevance of genetic variability to the pathogenesis of chagas disease, " Memorias do Instituto Oswaldo Cruz, vol. 99, no. 1, pp. 1-12, 2004.