1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Pathology: Mechanisms of Disease
  4. Volume 14, 2019
  5. Article

Annual Review of Pathology: Mechanisms of Disease

Volume 14, 2019

Pathology and Pathogenesis of Chagas Heart Disease

Abstract

Chagas heart disease is an inflammatory cardiomyopathy that develops in approximately one-third of people infected with the protozoan parasite . One way is transmitted to people is through contact with infected kissing bugs, which are found in much of the Western Hemisphere, including in vast areas of the United States. The epidemiology of and Chagas heart disease and the varied mechanisms leading to myocyte destruction, mononuclear cell infiltration, fibrosis, and edema in the heart have been extensively studied by hundreds of scientists for more than 100 years. Despite this wealth of knowledge, it is still impossible to predict what will happen in an individual infected with because of the tremendous variability in clonal parasite virulence and human susceptibility to infection and the lack of definitive molecular predictors of outcome from either side of the host–parasite equation. Further, while several distinct mechanisms of pathogenesis have been studied in isolation, it is certain that multiple coincident mechanisms combine to determine the ultimate outcome. For these reasons, Chagas disease is best considered a collection of related but distinct illnesses. This review highlights the pathology and pathogenesis of the most common adverse sequela of infection—Chagas heart disease—and concludes with a discussion of key unanswered questions and a view to the future.

Keyword(s): cardiomyopathy, Chagas, heart, myocarditis, pathogenesis, trypanosome
Loading

Article metrics loading...

/content/journals/10.1146/annurev-pathol-020117-043711
2019-01-24
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/pathmechdis/14/1/annurev-pathol-020117-043711.html?itemId=/content/journals/10.1146/annurev-pathol-020117-043711&mimeType=html&fmt=ahah

Literature Cited

  1. 1.  Brener Z 1973. Biology of Trypanosoma cruzi. Annu. Rev. Microbiol 27:347–82
     [Google Scholar]
  2. 2. WHO (World Health Organ.). 2002. Control of Chagas Disease: Second Report of the WHO Expert Committee Geneva, Switzerland: WHO
  3. 3.  Shikanai-Yasuda MA, Carvalho NB 2012. Oral transmission of Chagas disease. Clin. Infect. Dis. 54:845–52
     [Google Scholar]
  4. 4.  Tanowitz HB, Weiss LM, Montgomery SP 2011. Chagas disease has now gone global. PLOS Negl. Trop. Dis. 5:e1136
     [Google Scholar]
  5. 5. PAHO (Pan Am. Health Organ.). 2018. Chagas disease portal. Pan Am. Health Organ. http://www.paho.org/hq/index.php?option=com_topics&view=article&id=10&Itemid=40743&lang=en
  6. 6.  Guedes PM, Silva GK, Gutierrez FR, Silva JS 2011. Current status of Chagas disease chemotherapy. Expert Rev. Anti. Infect. Ther. 9:609–20
     [Google Scholar]
  7. 7.  Morillo CA, Marin-Neto JA, Avezum A, Sosa-Estani S, Rassi A Jr et al. 2015. Randomized trial of benznidazole for chronic Chagas’ cardiomyopathy. N. Engl. J. Med. 373:1295–306
     [Google Scholar]
  8. 8.  Pecoul B, Batista C, Stobbaerts E, Ribeiro I, Vilasanjuan R et al. 2016. The BENEFIT Trial: Where do we go from here?. PLOS Negl. Trop. Dis. 10:e0004343
     [Google Scholar]
  9. 9.  Beaumier CM, Gillespie PM, Strych U, Hayward T, Hotez PJ, Bottazzi ME 2016. Status of vaccine research and development of vaccines for Chagas disease. Vaccine 34:2996–3000
     [Google Scholar]
  10. 10.  Tanowitz HB, Kirchhoff LV, Simon D, Morris SA, Weiss LM, Wittner M 1992. Chagas’ disease. Clin. Microbiol. Rev. 5:400–19
     [Google Scholar]
  11. 11.  Benziger CP, do Carmo GAL, Ribeiro ALP 2017. Chagas cardiomyopathy: clinical presentation and management in the Americas. Cardiol. Clin. 35:31–47
     [Google Scholar]
  12. 12.  Linhares-Lacerda L, Granato A, Gomes-Neto JF, Conde L, Freire-de-Lima L et al. 2018. Circulating plasma microRNA-208a as potential biomarker of chronic indeterminate phase of Chagas disease. Front. Microbiol. 9:269
     [Google Scholar]
  13. 13.  Tanowitz HB, Machado FS, Spray DC, Friedman JM, Weiss OS et al. 2016. Developments in the management of Chagas cardiomyopathy. Expert Rev. Cardiovasc. Ther. 13:1393–409
     [Google Scholar]
  14. 14.  Matsuda NM, Miller SM, Evora PR 2009. The chronic gastrointestinal manifestations of Chagas disease. Clinics 64:1219–24
     [Google Scholar]
  15. 15.  Perez-Ayala A, Perez-Molina JA, Norman F, Monge-Maillo B, Faro MV, Lopez-Velez R 2011. Gastro-intestinal Chagas disease in migrants to Spain: prevalence and methods for early diagnosis. Ann. Trop. Med. Parasitol. 105:25–29
     [Google Scholar]
  16. 16.  Machado FS, Dutra WO, Esper L, Gollob KJ, Teixeira MM et al. 2012. Current understanding of immunity to Trypanosoma cruzi infection and pathogenesis of Chagas disease. Semin. Immunopathol. 34:753–70
     [Google Scholar]
  17. 17.  Higuchi MDL 1997. Chronic chagasic cardiopathy: the product of a turbulent host–parasite relationship. Rev. Inst. Med. Trop. Sao Paulo 39:53–60
     [Google Scholar]
  18. 18.  Teixeira AR, Nascimento RJ, Sturm NR 2006. Evolution and pathology in Chagas disease—a review. Mem. Inst. Oswaldo Cruz 101:463–91
     [Google Scholar]
  19. 19.  Tanowitz HB, Machado FS, Jelicks LA, Shirani J, de Carvalho AC et al. 2009. Perspectives on Trypanosoma cruzi–induced heart disease (Chagas disease). Prog. Cardiovasc. Dis. 51:524–39
     [Google Scholar]
  20. 20.  Lewis MD, Kelly JM 2016. Putting infection dynamics at the heart of Chagas disease. Trends Parasitol 32:899–911
     [Google Scholar]
  21. 21.  Ferreira AV, Segatto M, Menezes Z, Macedo AM, Gelape C et al. 2011. Evidence for Trypanosoma cruzi in adipose tissue in human chronic Chagas disease. Microbes Infect 13:1002–5
     [Google Scholar]
  22. 22.  Fernandes MC, Andrews NW 2012. Host cell invasion by Trypanosoma cruzi: a unique strategy that promotes persistence. FEMS Microbiol. Rev. 36:734–47
     [Google Scholar]
  23. 23.  Andrade ZA 1999. Immunopathology of Chagas disease. Mem. Inst. Oswaldo Cruz 94:Suppl. 171–80
     [Google Scholar]
  24. 24.  Jabari S, de Oliveira EC, Brehmer A, da Silveira AB 2014. Chagasic megacolon: enteric neurons and related structures. Histochem. Cell Biol. 142:235–44
     [Google Scholar]
  25. 25.  Alvarez JM, Fonseca R, Borges da Silva H, Marinho CR, Bortoluci KR et al. 2014. Chagas disease: still many unsolved issues. Mediat. Inflamm. 2014:912965
     [Google Scholar]
  26. 26.  Rossi MA, Ramos SG, Bestetti RB 2003. Chagas’ heart disease: clinical–pathological correlation. Front. Biosci. 8:e94–109
     [Google Scholar]
  27. 27.  Marcon GE, de Albuquerque DM, Batista AM, Andrade PD, Almeida EA et al. 2011. Trypanosoma cruzi: parasite persistence in tissues in chronic chagasic Brazilian patients. Mem. Inst. Oswaldo Cruz 106:85–91
     [Google Scholar]
  28. 28.  Rossi MA 1991. The pattern of myocardial fibrosis in chronic Chagas’ heart disease. Int. J. Cardiol. 30:335–40
     [Google Scholar]
  29. 29.  Rossi MA 1998. Fibrosis and inflammatory cells in human chronic chagasic myocarditis: scanning electron microscopy and immunohistochemical observations. Int. J. Cardiol. 66:183–94
     [Google Scholar]
  30. 30.  Roffe E, Marino AP, Weaver J, Wan W, de Araujo FF et al. 2016. Trypanosoma cruzi causes paralyzing systemic necrotizing vasculitis driven by pathogen-specific type I immunity in mice. Infect. Immun. 84:1123–36
     [Google Scholar]
  31. 31.  Marin-Neto JA, Simoes MV, Rassi A Jr 2013. Pathogenesis of chronic Chagas cardiomyopathy: the role of coronary microvascular derangements. Rev. Soc. Bras. Med. Trop 46:536–41
     [Google Scholar]
  32. 32.  Marin-Neto JA, Cunha-Neto E, Maciel BC, Simoes MV 2007. Pathogenesis of chronic Chagas heart disease. Circulation 115:1109–23
     [Google Scholar]
  33. 33.  Mello de Oliveira JA, Meira Oliveira JS, Koberle F 1972. Pathologic anatomy of the His-Tawara system and electrocardiographic abnormalities in chronic Chagas’ heart disease. Arq. Bras. Cardiol. 25:17–25
     [Google Scholar]
  34. 34.  Andrade ZA, Andrade SG, Sadigursky M, Camara EJ 1988. Pathology of complete atrioventricular block in chronic Chagas’ myocarditis. Rev. Soc. Bras. Med. Trop. 21:7–13
     [Google Scholar]
  35. 35.  Ramos SG, Matturri L, Rossi L, Rossi MA 1996. Lesions of mediastinal paraganglia in chronic chagasic cardiomyopathy: cause of sudden death?. Am. Heart J. 131:417–20
     [Google Scholar]
  36. 36.  Miranda CH, Figueiredo AB, Maciel BC, Marin-Neto JA, Simoes MV 2011. Sustained ventricular tachycardia is associated with regional myocardial sympathetic denervation assessed with 123I-metaiodobenzylguanidine in chronic Chagas cardiomyopathy. J. Nucl. Med. 52:504–10
     [Google Scholar]
  37. 37.  Rassi A Jr, Marin JAN, Rassi A 2017. Chronic Chagas cardiomyopathy: a review of the main pathogenic mechanisms and the efficacy of aetiological treatment following the BENznidazole Evaluation for Interrupting Trypanosomiasis (BENEFIT) Trial. Mem. Inst. Oswaldo Cruz 112:224–35
     [Google Scholar]
  38. 38.  Gutierrez FR, Guedes PM, Gazzinelli RT, Silva JS 2009. The role of parasite persistence in pathogenesis of Chagas heart disease. Parasite Immunol 31:673–85
     [Google Scholar]
  39. 39.  Lewis MD, Fortes Francisco A, Taylor MC, Burrell-Saward H, McLatchie AP et al. 2014. Bioluminescence imaging of chronic Trypanosoma cruzi infections reveals tissue-specific parasite dynamics and heart disease in the absence of locally persistent infection. Cell. Microbiol. 16:1285–300
     [Google Scholar]
  40. 40.  Bonney KM, Engman DM 2008. Chagas heart disease pathogenesis: one mechanism or many?. Curr. Mol. Med. 8:510–18
     [Google Scholar]
  41. 41.  Hyland KV, Leon JS, Daniels MD, Giafis N, Woods LM et al. 2007. Modulation of autoimmunity by treatment of an infectious disease. Infect. Immun. 75:3641–50
     [Google Scholar]
  42. 42.  Hyland KV, Asfaw SH, Olson CL, Daniels MD, Engman DM 2008. Bioluminescent imaging of Trypanosoma cruzi infection. Int. J. Parasitol. 38:1391–400
     [Google Scholar]
  43. 43.  Lewis MD, Francisco AF, Taylor MC, Jayawardhana S, Kelly JM 2016. Host and parasite genetics shape a link between Trypanosoma cruzi infection dynamics and chronic cardiomyopathy. Cell. Microbiol. 18:1429–43
     [Google Scholar]
  44. 44.  Lidani KCF, Bavia L, Ambrosio AR, de Messias-Reason IJ 2017. The complement system: a prey of Trypanosoma cruzi. Front. . Microbiol 8:607
     [Google Scholar]
  45. 45.  Rimoldi MT, Tenner AJ, Bobak DA, Joiner KA 1989. Complement component C1q enhances invasion of human mononuclear phagocytes and fibroblasts by Trypanosoma cruzi trypomastigotes. J. Clin. Investig. 84:1982–89
     [Google Scholar]
  46. 46.  Joiner K, Sher A, Gaither T, Hammer C 1986. Evasion of alternative complement pathway by Trypanosoma cruzi results from inefficient binding of factor B. PNAS 83:6593–97
     [Google Scholar]
  47. 47.  Zingales B 2017. Trypanosoma cruzi genetic diversity: something new for something known about Chagas disease manifestations, serodiagnosis and drug sensitivity. Acta Trop 184:38–52
     [Google Scholar]
  48. 48.  Benvenuti LA, Roggerio A, Cavalcanti MM, Nishiya AS, Levi JE 2017. An autopsy-based study of Trypanosoma cruzi persistence in organs of chronic chagasic patients and its relevance for transplantation. Transpl. Infect. Dis. 19:e12783
     [Google Scholar]
  49. 49.  Hotez PJ, Dumonteil E, Woc-Colburn L, Serpa JA, Bezek S et al. 2012. Chagas disease: “The new HIV/AIDS of the Americas. .” PLOS Negl. Trop. Dis. 6:e1498
     [Google Scholar]
  50. 50.  Kayama H, Takeda K 2010. The innate immune response to Trypanosoma cruzi infection. Microbes Infect 12:511–17
     [Google Scholar]
  51. 51.  Campos MA, Gazzinelli RT 2004. Trypanosoma cruzi and its components as exogenous mediators of inflammation recognized through Toll-like receptors. Mediat. Inflamm. 13:139–43
     [Google Scholar]
  52. 52.  Clay GM, Sutterwala FS, Wilson ME 2014. NLR proteins and parasitic disease. Immunol. Res. 59:142–52
     [Google Scholar]
  53. 53.  Zamboni DS, Lima-Junior DS 2015. Inflammasomes in host response to protozoan parasites. Immunol. Rev. 265:156–71
     [Google Scholar]
  54. 54.  Gurung P, Kanneganti TD 2016. Immune responses against protozoan parasites: a focus on the emerging role of Nod-like receptors. Cell. Mol. Life Sci. 73:3035–51
     [Google Scholar]
  55. 55.  Dhiman M, Garg NJ 2011. NADPH oxidase inhibition ameliorates Trypanosoma cruzi–induced myocarditis during Chagas disease. J. Pathol. 225:583–96
     [Google Scholar]
  56. 56.  Dhiman M, Garg NJ 2014. P47phox−/− mice are compromised in expansion and activation of CD8+ T cells and susceptible to Trypanosoma cruzi infection. PLOS Pathog 10:e1004516
     [Google Scholar]
  57. 57.  Bogdan C 2015. Nitric oxide synthase in innate and adaptive immunity: an update. Trends Immunol 36:161–78
     [Google Scholar]
  58. 58.  Alvarez MN, Peluffo G, Piacenza L, Radi R 2011. Intraphagosomal peroxynitrite as a macrophage-derived cytotoxin against internalized Trypanosoma cruzi: consequences for oxidative killing and role of microbial peroxiredoxins in infectivity. J. Biol. Chem. 286:6627–40
     [Google Scholar]
  59. 59.  Piacenza L, Peluffo G, Alvarez MN, Kelly JM, Wilkinson SR, Radi R 2008. Peroxiredoxins play a major role in protecting Trypanosoma cruzi against macrophage- and endogenously-derived peroxynitrite. Biochem. J. 410:359–68
     [Google Scholar]
  60. 60.  Koo SJ, Chowdhury IH, Szczesny B, Wan X, Garg NJ 2016. Macrophages promote oxidative metabolism to drive nitric oxide generation in response to Trypanosoma cruzi. Infect. . Immun 84:3527–41
     [Google Scholar]
  61. 61.  Piacenza L, Zago MP, Peluffo G, Alvarez MN, Basombrio MA, Radi R 2009. Enzymes of the antioxidant network as novel determiners of Trypanosoma cruzi virulence. Int. J. Parasitol. 39:1455–64
     [Google Scholar]
  62. 62.  Zago MP, Hosakote YM, Koo S-J, Dhiman M, Piñeyro MD et al. 2016. TcI isolates of Trypanosoma cruzi exploit the antioxidant network for enhanced intracellular survival in macrophages and virulence in mice. Infect. Immun. 84:1842–56
     [Google Scholar]
  63. 63.  Pineyro MD, Parodi-Talice A, Arcari T, Robello C 2008. Peroxiredoxins from Trypanosoma cruzi: virulence factors and drug targets for treatment of Chagas disease?. Gene 408:45–50
     [Google Scholar]
  64. 64.  Gupta S, Bhatia V, Wen J-J, Wu Y, Huang M-H, Garg NJ 2009. Trypanosoma cruzi infection disturbs mitochondrial membrane potential and ROS production rate in cardiomyocytes. Free Radic. Biol. Med. 47:1414–21
     [Google Scholar]
  65. 65.  Ba X, Gupta S, Davidson M, Garg NJ 2010. Trypanosoma cruzi induces the reactive oxygen species–PARP-1–RelA pathway for up-regulation of cytokine expression in cardiomyocytes. J. Biol. Chem. 285:11596–606
     [Google Scholar]
  66. 66.  Wan X, Wen JJ, Koo SJ, Liang LY, Garg NJ 2016. SIRT1–PGC1α–NFκB pathway of oxidative and inflammatory stress during Trypanosoma cruzi infection: benefits of SIRT1-targeted therapy in improving heart function in Chagas disease. PLOS Pathog 12:e1005954
     [Google Scholar]
  67. 67.  Keating SM, Deng X, Fernandes F, Cunha-Neto E, Ribeiro AL et al. 2015. Inflammatory and cardiac biomarkers are differentially expressed in clinical stages of Chagas disease. Int. J. Cardiol. 199:451–59
     [Google Scholar]
  68. 68.  Cunha-Neto E, Teixeira PC, Fonseca SG, Bilate AM, Kalil J 2011. Myocardial gene and protein expression profiles after autoimmune injury in Chagas’ disease cardiomyopathy. Autoimmun. Rev. 10:163–65
     [Google Scholar]
  69. 69.  Garg NJ, Soman KV, Zago MP, Koo SJ, Spratt H et al. 2016. Changes in proteome profile of peripheral blood mononuclear cells in chronic Chagas disease. PLOS Negl. Trop. Dis. 10:e0004490
     [Google Scholar]
  70. 70.  Ferreira LR, Ferreira FM, Nakaya HI, Deng X, Cândido DD et al. 2017. Blood gene signatures of Chagas disease cardiomyopathy with or without ventricular dysfunction. J. Infect. Dis. 215:387–95
     [Google Scholar]
  71. 71.  Souza PE, Rocha MO, Menezes CA, Coelho JS, Chaves AC 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. Infect. Immun. 75:1886–94
     [Google Scholar]
  72. 72.  Souza PE, Rocha MO, Rocha-Vieira E, Menezes CA, Chaves AC et al. 2004. Monocytes from patients with indeterminate and cardiac forms of Chagas’ disease display distinct phenotypic and functional characteristics associated with morbidity. Infect. Immun. 72:5283–91
     [Google Scholar]
  73. 73.  Machado FS, Dutra WO, Esper L, Gollob KJ, Teixeira MM et al. 2012. Current understanding of immunity to Trypanosoma cruzi infection and pathogenesis of Chagas disease. Semin. Immunopathol. 34:753–70
     [Google Scholar]
  74. 74.  Chowdhury IH, Koo SJ, Gupta S, Liang LY, Bahar B et al. 2017. Gene expression profiling and functional characterization of macrophages in response to circulatory microparticles produced during Trypanosoma cruzi infection and Chagas disease. J. Innate Immun. 9:203–16
     [Google Scholar]
  75. 75.  Dhiman M, Zago MP, Nunez S, Nunez-Burgio F, Garg NJ 2012. Cardiac oxidized antigens are targets of immune recognition by antibodies and potential molecular determinants in Chagas disease pathogenesis. PLOS ONE 7:e28449
     [Google Scholar]
  76. 76.  Tardieux I, Nathanson MH, Andrews NW 1994. Role in host cell invasion of Trypanosoma cruzi–induced cytosolic-free Ca2+ transients. J. Exp. Med. 179:1017–22
     [Google Scholar]
  77. 77.  Wen JJ, Garg NJ 2008. Mitochondrial generation of reactive oxygen species is enhanced at the Qo site of the complex III in the myocardium of Trypanosoma cruzi–infected mice: beneficial effects of an antioxidant. J. Bioenerg. Biomembr. 40:587–98
     [Google Scholar]
  78. 78.  Wen J-J, Garg NJ 2010. Mitochondrial complex III defects contribute to inefficient respiration and ATP synthesis in the myocardium of Trypanosoma cruzi–infected mice. Antioxid. Redox Signal. 12:27–37
     [Google Scholar]
  79. 79.  Wen JJ, Dhiman M, Whorton EB, Garg NJ 2008. Tissue-specific oxidative imbalance and mitochondrial dysfunction during Trypanosoma cruzi infection in mice. Microbes Infect 10:1201–9
     [Google Scholar]
  80. 80.  Perez-Fuentes R, Guegan JF, Barnabe C, Lopez-Colombo A, Salgado-Rosas H et al. 2003. Severity of chronic Chagas disease is associated with cytokine/antioxidant imbalance in chronically infected individuals. Int. J. Parasitol. 33:293–99
     [Google Scholar]
  81. 81.  de Oliveira TB, Pedrosa RC, Filho DW 2007. Oxidative stress in chronic cardiopathy associated with Chagas disease. Int. J. Cardiol. 116:357–63
     [Google Scholar]
  82. 82.  Wen J-J, Yachelini PC, Sembaj A, Manzur RE, Garg NJ 2006. Increased oxidative stress is correlated with mitochondrial dysfunction in chagasic patients. Free Radic. Biol. Med. 41:270–76
     [Google Scholar]
  83. 83.  Wan X-X, Gupta S, Zago MP, Davidson MM, Dousset P et al. 2012. Defects of mtDNA replication impaired the mitochondrial biogenesis during Trypanosoma cruzi infection in human cardiomyocytes and chagasic patients: the role of Nrf1/2 and antioxidant response. J. Am. Heart Assoc. 1:e003855
     [Google Scholar]
  84. 84.  Wen J-J, Gupta S, Guan Z, Dhiman M, Condon D et al. 2010. Phenyl-α-tert-butyl-nitrone and benzonidazole treatment controlled the mitochondrial oxidative stress and evolution of cardiomyopathy in chronic chagasic rats. J. Am. Coll. Cardiol. 55:2499–508
     [Google Scholar]
  85. 85.  Wen JJ, Porter C, Garg NJ 2017. Inhibition of NFE2L2–ARE pathway by mitochondrial ROS contributes to development of cardiomyopathy and left ventricular dysfunction in Chagas disease. Antioxid. Redox Signal. 27:550–66
     [Google Scholar]
  86. 86.  Panis C, Mazzuco TL, Costa CZ, Victorino VJ, Tatakihara VL et al. 2011. Trypanosoma cruzi: effect of the absence of 5-lipoxygenase (5-LO)–derived leukotrienes on levels of cytokines, nitric oxide and iNOS expression in cardiac tissue in the acute phase of infection in mice. Exp. Parasitol. 127:58–65
     [Google Scholar]
  87. 87.  Wen JJ, Wan X, Thacker J, Garg NJ 2016. Chemotherapeutic efficacy of phosphodiesterase inhibitors in chagasic cardiomyopathy. JACC Basic Transl. Sci. 1:235–50
     [Google Scholar]
  88. 88.  D'Avila H, Toledo DA, Melo RC 2012. Lipid bodies: inflammatory organelles implicated in host–Trypanosoma cruzi interplay during innate immune responses. Mediat. Inflamm. 2012:478601
     [Google Scholar]
  89. 89.  Canavaci AM, Sorgi CA, Martins VP, Morais FR, de Sousa EV et al. 2014. The acute phase of Trypanosoma cruzi infection is attenuated in 5-lipoxygenase-deficient mice. Mediat. Inflamm. 2014:893634
     [Google Scholar]
  90. 90.  Pavanelli WR, Gutierrez FR, Mariano FS, Prado CM, Ferreira BR et al. 2010. 5-lipoxygenase is a key determinant of acute myocardial inflammation and mortality during Trypanosoma cruzi infection. Microbes Infect 12:587–97
     [Google Scholar]
  91. 91.  Esper L, Roman-Campos D, Lara A, Brant F, Castro LL et al. 2012. Role of SOCS2 in modulating heart damage and function in a murine model of acute Chagas disease. Am. J. Pathol. 181:130–40
     [Google Scholar]
  92. 92.  Tanowitz HB, Mukhopadhyay A, Ashton AW, Lisanti MP, Machado FS et al. 2011. Microarray analysis of the mammalian thromboxane receptor–Trypanosoma cruzi interaction. Cell Cycle 10:1132–43
     [Google Scholar]
  93. 93.  Vago AR, Andrade LO, Leite AA, d'Avila Reis D, Macedo AM et al. 2000. Genetic characterization of Trypanosoma cruzi directly from tissues of patients with chronic Chagas disease: differential distribution of genetic types into diverse organs. Am. J. Pathol. 156:1805–9
     [Google Scholar]
  94. 94.  dos Santos DM, Talvani A, Guedes PM, Machado-Coelho GL, de Lana M, Bahia MT 2009. Trypanosoma cruzi: Genetic diversity influences the profile of immunoglobulins during experimental infection. Exp. Parasitol. 121:8–14
     [Google Scholar]
  95. 95.  Scharfstein J, Andrade D 2011. Infection-associated vasculopathy in experimental Chagas disease: pathogenic roles of endothelin and kinin pathways. Adv. Parasitol. 76:101–27
     [Google Scholar]
  96. 96.  Scharfstein J, Schmitz V, Svensjo E, Granato A, Monteiro AC 2007. Kininogens coordinate adaptive immunity through the proteolytic release of bradykinin, an endogenous danger signal driving dendritic cell maturation. Scand. J. Immunol. 66:128–36
     [Google Scholar]
  97. 97.  Scharfstein J, Ramos PIP, Barral-Netto M 2017. G protein–coupled kinin receptors and immunity against pathogens. Adv. Immunol. 136:29–84
     [Google Scholar]
  98. 98.  Tanowitz HB, Jelicks LA, Machado FS, Esper L, Qi X et al. 2011. Adipose tissue, diabetes and Chagas disease. Adv. Parasitol. 76:235–50
     [Google Scholar]
  99. 99.  Nascimento CR, Andrade D, Carvalho-Pinto CE, Serra RR, Vellasco L et al. 2017. Mast cell coupling to the kallikrein–kinin system fuels intracardiac parasitism and worsens heart pathology in experimental Chagas disease. Front. Immunol. 8:840
     [Google Scholar]
  100. 100.  Tarleton RL 1990. Depletion of CD8+ T cells increases susceptibility and reverses vaccine-induced immunity in mice infected with Trypanosoma cruzi. J. . Immunol 144:717–24
     [Google Scholar]
  101. 101.  Tarleton RL, Sun J, Zhang L, Postan M 1994. Depletion of T-cell subpopulations results in exacerbation of myocarditis and parasitism in experimental Chagas’ disease. Infect. Immun. 62:1820–29
     [Google Scholar]
  102. 102.  Tarleton RL, Koller BH, Latour A, Postan M 1992. Susceptibility of β2-microglobulin-deficient mice to Trypanosoma cruzi infection. Nature 356:338–40
     [Google Scholar]
  103. 103.  Sathler-Avelar R, Vitelli-Avelar DM, Eloi-Santos SM, Gontijo ED, Teixeira-Carvalho A, Martins-Filho OA 2012. Blood leukocytes from benznidazole-treated indeterminate Chagas disease patients display an overall type-1-modulated cytokine profile upon short-term in vitro stimulation with Trypanosoma cruzi antigens. BMC Infect. Dis. 12:123
     [Google Scholar]
  104. 104.  Guedes PM, Gutierrez FR, Silva GK, Dellalibera-Joviliano R, Rodrigues GJ et al. 2012. Deficient regulatory T cell activity and low frequency of IL-17-producing T cells correlate with the extent of cardiomyopathy in human Chagas’ disease. PLOS Negl. Trop. Dis. 6:e1630
     [Google Scholar]
  105. 105.  Guo S, Cobb D, Smeltz RB 2009. T-bet inhibits the in vivo differentiation of parasite-specific CD4+ Th17 cells in a T cell–intrinsic manner. J. Immunol. 182:6179–86
     [Google Scholar]
  106. 106.  Cunha-Neto E, Kalil J 2001. Heart-infiltrating and peripheral T cells in the pathogenesis of human Chagas’ disease cardiomyopathy. Autoimmunity 34:187–92
     [Google Scholar]
  107. 107.  Dutra WO, Gollob KJ, Pinto-Dias JC, Gazzinelli G, Correa-Oliveira R et al. 1997. Cytokine mRNA profile of peripheral blood mononuclear cells isolated from individuals with Trypanosoma cruzi chronic infection. Scand. J. Immunol. 45:74–80
     [Google Scholar]
  108. 108.  Gomes JA, Bahia-Oliveira LM, Rocha MO, Martins-Filho OA, Gazzinelli G, Correa-Oliveira R 2003. Evidence that development of severe cardiomyopathy in human Chagas’ disease is due to a Th1-specific immune response. Infect. Immun. 71:1185–93
     [Google Scholar]
  109. 109.  Da Matta Guedes PM, Gutierrez FR, Maia FL, Milanezi CM, Silva GK et al. 2010. IL-17 produced during Trypanosoma cruzi infection plays a central role in regulating parasite-induced myocarditis. PLOS Negl. Trop. Dis. 4:e604
     [Google Scholar]
  110. 110.  Martin D, Tarleton R 2004. Generation, specificity, and function of CD8+ T cells in Trypanosoma cruzi infection. Immunol. Rev. 201:304–17
     [Google Scholar]
  111. 111.  Mateus J, Perez-Anton E, Lasso P, Egui A, Roa N et al. 2017. Antiparasitic treatment induces an improved CD8+ T cell response in chronic chagasic patients. J. Immunol. 198:3170–80
     [Google Scholar]
  112. 112.  Albareda MC, Laucella SA, Alvarez MG, Armenti AH, Bertochi G et al. 2006. Trypanosoma cruzi modulates the profile of memory CD8+ T cells in chronic Chagas’ disease patients. Int. Immunol. 18:465–71
     [Google Scholar]
  113. 113.  Cai CW, Blase JR, Zhang X, Eickhoff CS, Hoft DF 2016. Th17 cells are more protective than Th1 cells against the intracellular parasite Trypanosoma cruzi. . PLOS Pathog 12:e1005902
     [Google Scholar]
  114. 114.  Rocha Rodrigues DB, dos Reis MA, Romano A, Pereira SADL, Teixeira VDPA et al. 2012. In situ expression of regulatory cytokines by heart inflammatory cells in Chagas’ disease patients with heart failure. Clin. Dev. Immunol. 2012:361730
     [Google Scholar]
  115. 115.  Cunha-Neto E, Dzau VJ, Allen PD, Stamatiou D, Benvenutti L et al. 2005. Cardiac gene expression profiling provides evidence for cytokinopathy as a molecular mechanism in Chagas’ disease cardiomyopathy. Am. J. Pathol. 167:305–13
     [Google Scholar]
  116. 116.  Ruiz Diaz P, Mucci J, Meira MA, Bogliotti Y, Musikant D et al. 2015. Trypanosoma cruzi trans-sialidase prevents elicitation of Th1 cell response via interleukin 10 and downregulates Th1 effector cells. Infect. Immun. 83:2099–108
     [Google Scholar]
  117. 117.  Rodriguez-Angulo H, Marques J, Mendoza I, Villegas M, Mijares A et al. 2017. Differential cytokine profiling in chagasic patients according to their arrhythmogenic-status. BMC Infect. Dis. 17:221
     [Google Scholar]
  118. 118.  Mateus J, Lasso P, Pavia P, Rosas F, Roa N et al. 2015. Low frequency of circulating CD8+ T stem cell memory cells in chronic chagasic patients with severe forms of the disease. PLOS Negl. Trop. Dis. 9:e3432
     [Google Scholar]
  119. 119.  Arguello RJ, Vigliano C, Cabeza-Meckert P, Viotti R, Garelli F et al. 2014. Presence of antigen-experienced T cells with low grade of differentiation and proliferative potential in chronic Chagas disease myocarditis. PLOS Negl. Trop. Dis. 8:e2989
     [Google Scholar]
  120. 120.  Giraldo NA, Bolanos NI, Cuellar A, Guzman F, Uribe AM et al. 2011. Increased CD4+/CD8+ double-positive T cells in chronic chagasic patients. PLOS Negl. Trop. Dis. 5:e1294
     [Google Scholar]
  121. 121.  Dutra WO, Martins-Filho OA, Cancado JR, Pinto-Dias JC, Brener Z et al. 1994. Activated T and B lymphocytes in peripheral blood of patients with Chagas’ disease. Int. Immunol. 6:499–506
     [Google Scholar]
  122. 122.  Higuchi ML, De Morais CF, Pereira Barreto AC, Lopes EA, Stolf N et al. 1987. The role of active myocarditis in the development of heart failure in chronic Chagas’ disease: a study based on endomyocardial biopsies. Clin. Cardiol. 10:665–70
     [Google Scholar]
  123. 123.  Dos Santos Virgilio F, Pontes C, Dominguez MR, Ersching J, Rodrigues MM, Vasconcelos JR 2014. CD8+ T cell-mediated immunity during Trypanosoma cruzi infection: a path for vaccine development?. Mediat. Inflamm. 2014:243786
     [Google Scholar]
  124. 124.  Cunha-Neto E, Kalil J 1995. Autoimmunity in Chagas’ heart disease. Sao Paulo Med. J. 113:757–66
     [Google Scholar]
  125. 125.  Teixeira AR, Nitz N, Bernal FM, Hecht MM 2012. Parasite induced genetically driven autoimmune Chagas heart disease in the chicken model. J. Vis. Exp. 65:e3716
     [Google Scholar]
  126. 126.  Girones N, Carrasco-Marin E, Cuervo H, Guerrero NA, Sanoja C et al. 2007. Role of Trypanosoma cruzi autoreactive T cells in the generation of cardiac pathology. Ann. N. Y. Acad. Sci. 1107:434–44
     [Google Scholar]
  127. 127.  Bonney KM, Engman DM 2015. Autoimmune pathogenesis of Chagas heart disease: looking back, looking ahead. Am. J. Pathol. 185:1537–47
     [Google Scholar]
  128. 128.  Vitelli-Avelar DM, Sathler-Avelar R, Massara RL, Borges JD, Lage PS et al. 2006. Are increased frequency of macrophage-like and natural killer (NK) cells, together with high levels of NKT and CD4+CD25high T cells balancing activated CD8+ T cells, the key to control Chagas’ disease morbidity?. Clin. Exp. Immunol. 145:81–92
     [Google Scholar]
  129. 129.  Vitelli-Avelar DM, Sathler-Avelar R, Dias JC, Pascoal VP, Teixeira-Carvalho A et al. 2005. Chagasic patients with indeterminate clinical form of the disease have high frequencies of circulating CD3+CD16−CD56+ natural killer T cells and CD4+CD25High regulatory T lymphocytes. Scand. J. Immunol. 62:297–308
     [Google Scholar]
  130. 130.  Mariano FS, Gutierrez FR, Pavanelli WR, Milanezi CM, Cavassani KA et al. 2008. The involvement of CD4+CD25+ T cells in the acute phase of Trypanosoma cruzi infection. Microbes Infect 10:825–33
     [Google Scholar]
  131. 131.  Sales PA Jr, Golgher D, Oliveira RV, Vieira V, Arantes RM et al. 2008. The regulatory CD4+CD25+ T cells have a limited role on pathogenesis of infection with Trypanosoma cruzi. . Microbes Infect 10:680–88
     [Google Scholar]
  132. 132.  Bonney KM, Taylor JM, Thorp EB, Epting CL, Engman DM 2015. Depletion of regulatory T cells decreases cardiac parasitosis and inflammation in experimental Chagas disease. Parasitol. Res. 114:1167–78
     [Google Scholar]
  133. 133.  Nihei J, Cardillo F, Dos Santos WL, Pontes-de-Carvalho L, Mengel J 2014. Administration of a nondepleting anti-CD25 monoclonal antibody reduces disease severity in mice infected with Trypanosoma cruzi. Eur. J. Microbiol. Immunol 4:128–37
     [Google Scholar]
  134. 134.  Calzada JE, Beraun Y, Gonzalez CI, Martin J 2009. Transforming growth factor beta 1 (TGFβ1) gene polymorphisms and Chagas disease susceptibility in Peruvian and Colombian patients. Cytokine 45:149–53
     [Google Scholar]
  135. 135.  Altara R, Mallat Z, Booz GW, Zouein FA 2016. The CXCL10/CXCR3 axis and cardiac inflammation: implications for immunotherapy to treat infectious and noninfectious diseases of the heart. J. Immunol. Res. 2016:4396368
     [Google Scholar]
  136. 136.  Gil-Jaramillo N, Motta FN, Favali CB, Bastos IM, Santana JM 2016. Dendritic cells: a double-edged sword in immune responses during Chagas disease. Front. Microbiol. 7:1076
     [Google Scholar]
  137. 137.  Saraiva RM, Waghabi MC, Vilela MF, Madeira FS, Sperandio da Silva GM et al. 2013. Predictive value of transforming growth factor-β1 in Chagas disease: towards a biomarker surrogate of clinical outcome. Trans. R. Soc. Trop. Med. Hyg. 107:518–25
     [Google Scholar]
  138. 138.  Araujo-Jorge TC, Waghabi MC, Bailly S, Feige JJ 2012. The TGF-β pathway as an emerging target for Chagas disease therapy. Clin. Pharmacol. Ther. 92:613–21
     [Google Scholar]
  139. 139.  Curvo EO, Ferreira RR, Madeira FS, Alves GF, Chambela MC et al. 2018. Correlation of transforming growth factor-β1 and tumour necrosis factor levels with left ventricular function in Chagas disease. Mem. Inst. Oswaldo Cruz 113:e170440
     [Google Scholar]
  140. 140.  Kierszenbaum F, Cuna WR, Beltz LA, Sztein MB 1990. Trypanosomal immunosuppressive factor: a secretion product(s) of Trypanosoma cruzi that inhibits proliferation and IL-2 receptor expression by activated human peripheral blood mononuclear cells. J. Immunol. 144:4000–4
     [Google Scholar]
  141. 141.  Sztein MB, Cuna WR, Kierszenbaum F 1990. Trypanosoma cruzi inhibits the expression of CD3, CD4, CD8, and IL-2R by mitogen-activated helper and cytotoxic human lymphocytes. J. Immunol. 144:3558–62
     [Google Scholar]
  142. 142.  Costa RP, Gollob KJ, Fonseca LL, Rocha MO, Chaves AC et al. 2000. T-cell repertoire analysis in acute and chronic human Chagas’ disease: differential frequencies of Vβ5 expressing T cells. Scand. J. Immunol. 51:511–19
     [Google Scholar]
  143. 143.  Bermejo DA, Amezcua Vesely MC, Khan M, Acosta Rodriguez EV, Montes CL et al. 2011. Trypanosoma cruzi infection induces a massive extrafollicular and follicular splenic B-cell response which is a high source of non-parasite-specific antibodies. Immunology 132:123–33
     [Google Scholar]
  144. 144.  Antas PR, Medrano-Mercado N, Torrico F, Ugarte-Fernandez R, Gomez F et al. 1999. Early, intermediate, and late acute stages in Chagas’ disease: a study combining anti-galactose IgG, specific serodiagnosis, and polymerase chain reaction analysis. Am. J. Trop. Med. Hyg. 61:308–14
     [Google Scholar]
  145. 145.  Jackson Y, Chatelain E, Mauris A, Holst M, Miao Q et al. 2013. Serological and parasitological response in chronic Chagas patients 3 years after nifurtimox treatment. BMC Infect. Dis. 13:85
     [Google Scholar]
  146. 146.  Zrein M, Granjon E, Gueyffier L, Caillaudeau J, Liehl P et al. 2018. A novel antibody surrogate biomarker to monitor parasite persistence in Trypanosoma cruzi–infected patients. PLOS Negl. Trop. Dis. 12:e0006226
     [Google Scholar]
  147. 147.  Cordeiro FD, Martins-Filho OA, Da Costa Rocha MO, Adad SJ, Correa-Oliveira R, Romanha AJ 2001. Anti-Trypanosoma cruzi immunoglobulin G1 can be a useful tool for diagnosis and prognosis of human Chagas' disease. Clin. Diagn. Lab. Immunol. 8:112–18
     [Google Scholar]
  148. 148.  Galvao LM, Nunes RM, Cancado JR, Brener Z, Krettli AU 1993. Lytic antibody titre as a means of assessing cure after treatment of Chagas disease: a 10 year follow-up study. Trans. R. Soc. Trop. Med. Hyg. 87:220–23
     [Google Scholar]
  149. 149.  Gazzinelli RT, Pereira ME, Romanha A, Gazzinelli G, Brener Z 1991. Direct lysis of Trypanosoma cruzi: a novel effector mechanism of protection mediated by human anti-gal antibodies. Parasite Immunol 13:345–56
     [Google Scholar]
  150. 150.  Scott MT, Moyes L 1982. 75Se-methionine labelled Trypanosoma cruzi blood trypomastigotes: opsonization by chronic infection serum facilitates killing in spleen and liver. Clin. Exp. Immunol. 48:754–57
     [Google Scholar]
  151. 151.  Gao W, Wortis HH, Pereira MA 2002. The Trypanosoma cruzi trans-sialidase is a T cell–independent B cell mitogen and an inducer of non-specific Ig secretion. Int. Immunol. 14:299–308
     [Google Scholar]
  152. 152.  Reina-San-Martin B, Degrave W, Rougeot C, Cosson A, Chamond N et al. 2000. A B-cell mitogen from a pathogenic trypanosome is a eukaryotic proline racemase. Nat. Med. 6:890–97
     [Google Scholar]
  153. 153.  Bryan MA, Norris KA 2010. Genetic immunization converts the Trypanosoma cruzi B-cell mitogen proline racemase to an effective immunogen. Infect. Immun. 78:810–22
     [Google Scholar]
  154. 154.  Laguens RP, Meckert PC, Chambo JG 1988. Antiheart antibody–dependent cytotoxicity in the sera from mice chronically infected with Trypanosoma cruzi. Infect. . Immun 56:993–97
     [Google Scholar]
  155. 155.  Bonney KM, Taylor JM, Daniels MD, Epting CL, Engman DM 2011. Heat-killed Trypanosoma cruzi induces acute cardiac damage and polyantigenic autoimmunity. PLOS ONE 6:e14571
     [Google Scholar]
  156. 156.  Daliry A, Pereira IR, Pereira-Junior PP, Ramos IP, Vilar-Pereira G et al. 2014. Levels of circulating anti-muscarinic and anti-adrenergic antibodies and their effect on cardiac arrhythmias and dysautonomia in murine models of Chagas disease. Parasitology 141:1769–78
     [Google Scholar]
  157. 157.  Florea F, Bernards C, Caproni M, Kleindienst J, Hashimoto T et al. 2014. Ex vivo pathogenicity of anti-laminin γ1 autoantibodies. Am. J. Pathol. 184:494–506
     [Google Scholar]
  158. 158.  Giordanengo L, Gea S, Barbieri G, Rabinovich GA 2001. Anti-galectin-1 autoantibodies in human Trypanosoma cruzi infection: differential expression of this β-galactoside-binding protein in cardiac Chagas’ disease. Clin. Exp. Immunol. 124:266–73
     [Google Scholar]
  159. 159.  Rodeles LM, Vicco MH, Bontempi IA, Siano A, Tonarelli G et al. 2016. Combined analysis of cross-reacting antibodies anti-β1AR and anti-B13 in advanced stages of Chagas heart disease. Trop. Med. Int. Health 21:1545–51
     [Google Scholar]
  160. 160.  Bonney KM, Gifford KM, Taylor JM, Chen CI, Engman DM 2013. Cardiac damage induced by immunization with heat-killed Trypanosoma cruzi is not antibody mediated. Parasite Immunol 35:1–10
     [Google Scholar]
  161. 161.  Talvani A, Rocha MO, Ribeiro AL, Borda E, Sterin-Borda L, Teixeira MM 2006. Levels of anti-M2 and anti-β1 autoantibodies do not correlate with the degree of heart dysfunction in Chagas’ heart disease. Microbes Infect 8:2459–64
     [Google Scholar]
  162. 162.  Lv H, Lipes MA 2012. Role of impaired central tolerance to α-myosin in inflammatory heart disease. Trends Cardiovasc. Med. 22:113–17
     [Google Scholar]
  163. 163.  Cunha-Neto E, Bilate AM, Hyland KV, Fonseca SG, Kalil J, Engman DM 2006. Induction of cardiac autoimmunity in Chagas heart disease: a case for molecular mimicry. Autoimmunity 39:41–54
     [Google Scholar]
  164. 164.  Machado FS, Tyler KM, Brant F, Esper L, Teixeira MM, Tanowitz HB 2012. Pathogenesis of Chagas disease: time to move on. Front. Biosci. 4:1743–58
     [Google Scholar]
  165. 165.  Cruz JS, Santos-Miranda A, Sales-Junior PA, Monti-Rocha R, Campos PP et al. 2016. Altered cardiomyocyte function and Trypanosoma cruzi persistence in Chagas disease. Am. J. Trop. Med. Hyg. 94:1028–33
     [Google Scholar]
  166. 166.  Nagajyothi F, Machado FS, Burleigh BA, Jelicks LA, Scherer PE et al. 2012. Mechanisms of Trypanosoma cruzi persistence in Chagas disease. Cell. Microbiol. 14:634–43
     [Google Scholar]
  167. 167.  Girones N, Cuervo H, Fresno M 2005. Trypanosoma cruzi–induced molecular mimicry and Chagas’ disease. Curr. Top. Microbiol. Immunol. 296:89–123
     [Google Scholar]
  168. 168.  Teixeira AR, Hecht MM, Guimaro MC, Sousa AO, Nitz N 2011. Pathogenesis of Chagas’ disease: parasite persistence and autoimmunity. Clin. Microbiol. Rev. 24:592–630
     [Google Scholar]
  169. 169.  Zingales B, Miles MA, Campbell DA, Tibayrenc M, Macedo AM et al. 2012. The revised Trypanosoma cruzi subspecific nomenclature: rationale, epidemiological relevance and research applications. Infect. Genet. Evol. 12:240–53
     [Google Scholar]
  170. 170.  Morillo CA, Marin-Neto JA, Avezum A, Sosa-Estani S, Rassi A Jr et al. 2015. Randomized trial of benznidazole for chronic Chagas’ cardiomyopathy. N. Engl. J. Med. 373:1295–306
     [Google Scholar]
  171. 171.  Bern C, Montgomery SP 2009. An estimate of the burden of Chagas disease in the United States. Clin. Infect. Dis. 49:e52–54
     [Google Scholar]
  172. 172.  Meymandi SK, Forsyth CJ, Soverow J, Hernandez S, Sanchez D et al. 2017. Prevalence of Chagas disease in the Latin American–born population of Los Angeles. Clin. Infect. Dis. 64:1182–88
     [Google Scholar]
  173. 173.  Curtis-Robles R, Auckland LD, Snowden KF, Hamer GL, Hamer SA 2018. Analysis of over 1500 triatomine vectors from across the US, predominantly Texas, for Trypanosoma cruzi infection and discrete typing units. Infect. Genet. Evol. 58:171–80
     [Google Scholar]
  174. 174.  Woody NC, Woody HB 1955. American trypanosomiasis (Chagas’ disease): first indigenous case in the United States. JAMA 159:676–77
     [Google Scholar]
  175. 175.  Barth E, Kundrotas L 2011. Megacolon from Chagas disease in an ancient Texan. Gastroenterology 141:35–404
     [Google Scholar]
  176. 176.  Zabalgoitia M, Ventura J, Anderson L, Carey KD, Williams JT, Vandeberg JL 2003. Morphologic and functional characterization of chagasic heart disease in non-human primates. Am. J. Trop. Med. Hyg. 68:248–52
     [Google Scholar]
  177. 177.  Meyers AC, Meinders M, Hamer SA 2017. Widespread Trypanosoma cruzi infection in government working dogs along the Texas–Mexico border: discordant serology, parasite genotyping and associated vectors. PLOS Negl. Trop. Dis. 11:e0005819
     [Google Scholar]
  178. 178.  Cantey PT, Stramer SL, Townsend RL, Kamel H, Ofafa K et al. 2012. The United States Trypanosoma cruzi Infection Study: evidence for vector-borne transmission of the parasite that causes Chagas disease among United States blood donors. Transfusion 52:1922–30
     [Google Scholar]
  179. 179.  Garcia MN, Aguilar D, Gorchakov R, Rossmann SN, Montgomery SP et al. 2015. Evidence of autochthonous Chagas disease in southeastern Texas. Am. J. Trop. Med. Hyg. 92:325–30
     [Google Scholar]
  180. 180.  Kransdorf EP, Fishbein MC, Czer LS, Patel JK, Velleca A et al. 2016. Pathology of chronic Chagas cardiomyopathy in the United States: a detailed review of 13 cardiectomy cases. Am. J. Clin. Pathol. 146:191–98
     [Google Scholar]
  181. 181.  Cardillo F, de Pinho RT, Antas PR, Mengel J 2015. Immunity and immune modulation in Trypanosoma cruzi infection. Pathog. Dis. 73:ftv082
     [Google Scholar]
  182. 182.  Coates BM, Sullivan DP, Makanji MY, Du NY, Olson CL et al. 2013. Endothelial transmigration by Trypanosoma cruzi. . PLOS ONE 8:e81187
     [Google Scholar]
/content/journals/10.1146/annurev-pathol-020117-043711
Loading
Pathology and Pathogenesis of Chagas Heart Disease
Annual Review of Pathology: Mechanisms of Disease 14, 421 (2019); https://doi.org/10.1146/annurev-pathol-020117-043711
/content/journals/10.1146/annurev-pathol-020117-043711
/content/journals/10.1146/annurev-pathol-020117-043711
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error