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Trypanosoma cruzi-Specific T-Cell Responses to Monitor Treatment Efficacy in Chronic Chagas Disease

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T. cruzi Infection

Abstract

Chagas disease is the highest impact parasitic disease in Latin America. In recent years, the use of immune-related biomarkers to predict diagnostic and treatment efficacy or to monitor diseases has been considered a promising tool. Our group has worked for the past 20 years on the characterization of different immunological aspects of the T-cell responses to T. cruzi antigens. We have shown that monitoring of appropriate immunological responses can provide earlier and robust measures of treatment.

The Enzyme-Linked ImmunoSPOT (ELISPOT) assays are powerful tools to evaluate antigen-specific immune responses at the single-cell level. Herein, we describe uses of the ELISPOT assay to determine the T. cruzi-specific T-cell populations in PBMCs from chronic chagasic subjects.

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References

  1. Feldman AM, McNamara D (2000) Myocarditis. N Engl J Med 343:1388–1398

    Article  CAS  PubMed  Google Scholar 

  2. Schmunis GA, Yadon ZE (2010) Chagas disease: a Latin American health problem becoming a world health problem. Acta Trop 115(1-2):14–21. https://doi.org/10.1016/j.actatropica.2009.11.003

    Article  PubMed  Google Scholar 

  3. Rosemberg S, Chaves CJ, Higuchi ML et al (1992) Fatal meningoencephalitis caused by reactivation of Trypanosoma cruzi infection in a patient with AIDS. Neurology 42:640–642

    Article  CAS  PubMed  Google Scholar 

  4. Silva N, O’Bryan L, Medeiros E et al (1999) Trypanosoma cruzi meningoencephalitis in HIV-infected patients. J Acquir Immune Defic Syndr Hum Retrovirol 20:342–349

    Article  CAS  PubMed  Google Scholar 

  5. Tarleton RL, Grusby MJ, Postan M et al (1996) Trypanosoma cruzi infection in MHC-deficient mice: further evidence for the role of both class I- and class II-restricted T cells in immune resistance and disease. Int Immunol 8(1):13–22

    Article  CAS  PubMed  Google Scholar 

  6. Fuenmayor C, Higuchi ML, Carrasco H et al (2005) Acute Chagas’ disease: immunohistochemical characteristics of T cell infiltrate and its relationship with T. cruzi parasitic antigens. Acta Cardiol 60(1):33–37

    Article  PubMed  Google Scholar 

  7. Tarleton RL (2007) Immune system recognition of Trypanosoma cruzi. Curr Opin Immunol 19(4):430–434

    Article  CAS  PubMed  Google Scholar 

  8. Tarleton RL (2003) Chagas disease: a role for autoimmunity? Trends Parasitol 19(10):447–451

    Article  CAS  PubMed  Google Scholar 

  9. Laucella SA, Postan M, Martin D et al (2004) Frequency of interferon- gamma -producing T cells specific for Trypanosoma cruzi inversely correlates with disease severity in chronic human Chagas disease. J Infect Dis 189(5):909–918

    Article  CAS  PubMed  Google Scholar 

  10. Albareda MC, Laucella SA, Alvarez MG et al (2006) Trypanosoma cruzi modulates the profile of memory CD8+ T cells in chronic Chagas’ disease patients. Int Immunol 18(3):465–471

    Article  CAS  PubMed  Google Scholar 

  11. Albareda MC, Olivera GC, Laucella SA et al (2009) Chronic human infection with Trypanosoma cruzi drives CD4+ T cells to immune senescence. J Immunol 183(6):4103–4108. https://doi.org/10.4049/jimmunol.0900852

    Article  CAS  PubMed  Google Scholar 

  12. Gutierrez FR, Guedes PM, Gazzinelli RT et al (2009) The role of parasite persistence in pathogenesis of Chagas heart disease. Parasite Immunol 31(11):673–685. https://doi.org/10.1111/j.1365-3024.2009.01108.x

    Article  CAS  PubMed  Google Scholar 

  13. Machado FS, Dutra WO, Esper L et al (2012) Current understanding of immunity to Trypanosoma cruzi infection and pathogenesis of Chagas disease. Semin Immunopathol 34(6):753–770. https://doi.org/10.1007/s00281-012-0351-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Altcheh J, Corral R, Biancardi MA et al (2003) Anti-F2/3 antibodies as cure marker in children with congenital Trypanosoma cruzi infection. Medicina (B Aires) 63(1):37–40

    Google Scholar 

  15. Sosa Estani S, Segura EL, Ruiz AM et al (1998) Efficacy of chemotherapy with benznidazole in children in the indeterminate phase of Chagas’ disease. Am J Trop Med Hyg 59(4):526–529

    Article  CAS  PubMed  Google Scholar 

  16. Sosa-Estani S, Viotti R, Segura EL (2009) Therapy, diagnosis and prognosis of chronic Chagas disease: insight gained in Argentina. Mem Inst Oswaldo Cruz 104(Suppl 1):167–180

    Article  PubMed  Google Scholar 

  17. Viotti R, Vigliano C, Armenti H et al (1994) Treatment of chronic Chagas disease with benznidazole: clinical and serologic evolution of patients with long-term follow-up. Am Heart J 127:151–162

    Article  CAS  PubMed  Google Scholar 

  18. Fabbro DL, Streiger ML, Arias ED et al (2007) Trypanocide treatment among adults with chronic Chagas disease living in Santa Fe city (Argentina) over a mean follow-up of 21 years: parasitological, serological and clinical evolution. Rev Soc Bras Med Trop 40:1–10

    Article  PubMed  Google Scholar 

  19. Bern C, Montgomery SP, Herwaldt BL et al (2007) Evaluation and treatment of Chagas disease in the United States: a systematic review. JAMA 298:2171–2181

    Article  CAS  PubMed  Google Scholar 

  20. Willis CD, Graham ML (2015) Immune biomarkers: the promises and pitfalls of personalized medicine. Nat Rev Immunol 15:323–329. https://doi.org/10.1038/nri3820

    Article  CAS  PubMed  Google Scholar 

  21. Cooley G, Etheridge RD, Boehlke C et al (2008) High throughput selection of effective serodiagnostics for Trypanosoma cruzi infection. PLoS Negl Trop Dis 2:e316. https://doi.org/10.1371/journal.pntd.0000316

    Article  PubMed  PubMed Central  Google Scholar 

  22. Laucella SA, Mazliah DP, Bertocchi G et al (2009) Changes in Trypanosoma cruzi-specific immune responses after treatment: surrogate markers of treatment efficacy. Clin Infect Dis 49:1675–1684. https://doi.org/10.1086/648072

    Article  CAS  PubMed  Google Scholar 

  23. Viotti R, Vigliano C, Alvarez MG et al (2011) Impact of aetiological treatment on conventional and multiplex serology in chronic Chagas disease. PLoS Negl Trop Dis 5(9):e1314. https://doi.org/10.1371/journal.pntd.0001314

    Article  PubMed  PubMed Central  Google Scholar 

  24. Alvarez MG, Bertocchi GL, Cooley G et al (2016) Treatment success in Trypanosoma cruzi infection is predicted by early changes in serially monitored parasite-specific T and B cell responses. PLoS Negl Trop Dis 10(4):e0004657. https://doi.org/10.1371/journal.pntd.0004657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Albareda MC, Natale MA, De Rissio AM, et al.(2018) Distinct Treatment Outcomes of Antiparasitic Therapy in Trypanosoma cruzi-Infected Children Is Associated With Early Changes in Cytokines, Chemokines, and T-Cell Phenotypes. Front Immunol 9:1958. https://doi.org/10.3389/fimmu.2018.01958

  26. Lalvani A, Brookes R, Hambleton S et al (1997) Rapid effector function in CD8+ memory T cells. J Exp Med 186(6):859–865. https://doi.org/10.1084/jem.186.6.859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Alvarez MG, Postan M, Weatherly DB et al (2008) HLA Class I-T cell epitopes from trans-sialidase proteins reveal functionally distinct subsets of CD8+ T cells in chronic Chagas disease. PLoS Negl Trop Dis 2(9):e288. https://doi.org/10.1371/journal.pntd.0000288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Scheibenbogen C, Romero P, Rivoltini L et al (2000) Quantitation of antigen-reactive T cells in peripheral blood by IFNgamma-ELISPOT assay and chromium-release assay: a four-centre comparative trial. J Immunol Methods 244(1–2):81–89. https://doi.org/10.1016/S0022-1759(00)00257-X

    Article  CAS  PubMed  Google Scholar 

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Albareda, M.C., Natale, M.A., Cesar, G.L., Castro Eiro, M.D., Alvarez, M.G., Laucella, S.A. (2019). Trypanosoma cruzi-Specific T-Cell Responses to Monitor Treatment Efficacy in Chronic Chagas Disease. In: Gómez, K., Buscaglia, C. (eds) T. cruzi Infection. Methods in Molecular Biology, vol 1955. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-9148-8_25

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  • DOI: https://doi.org/10.1007/978-1-4939-9148-8_25

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-9147-1

  • Online ISBN: 978-1-4939-9148-8

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