Chagas' Disease: an Update on Immune Mechanisms and Therapeutic Strategies

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2010 Jan 15

PMID 20070438

Citations 29

Authors

Silvia Beatriz Boscardin

Ana Claudia Troccoli Torrecilhas

Romina Manarin

Silvia Revelli

Elena Gonzalez Rey

Renata Rosito Tonelli

Ariel Mariano Silber

Affiliations

Soon will be listed here.

Abstract

* Introduction * Chagas' disease * Chemotherapy * Immune response in experimental T. cruzi infection * Immune response in human beings infected with T. cruzi * Immune response in the treatment of chagasic infection * The need for new therapeutic alternatives for Chagas' disease * Conclusions The final decade of the 20th century was marked by an alarming resurgence in infectious diseases caused by tropical parasites belonging to the kinetoplastid protozoan order. Among the pathogenic trypanosomatids, some species are of particular interest due to their medical importance. These species include the agent responsible for Chagas' disease, Trypanosoma cruzi. Approximately 8 to 10 million people are infected in the Americas, and approximately 40 million are at risk. In the present review, we discuss in detail the immune mechanisms elicited during infection by T. cruzi and the effects of chemotherapy in controlling parasite proliferation and on the host immune system.

Citing Articles

Reactivation After Chimeric Antigen Receptor T-Cell Therapy.

Alahmdi B, Kaur A, Jacobs S, Sullivan T, Barghash M, Taimur S Open Forum Infect Dis. 2024; 11(1):ofad698.

PMID: 38264096 PMC: 10804802. DOI: 10.1093/ofid/ofad698.

CCND1 Overexpression in Idiopathic Dilated Cardiomyopathy: A Promising Biomarker?.

Dehghani K, Stanek A, Bagherabadi A, Atashi F, Beygi M, Hooshmand A Genes (Basel). 2023; 14(6).

PMID: 37372424 PMC: 10298313. DOI: 10.3390/genes14061243.

Efficacy and Safety of Nifurtimox in Pediatric Patients with Chagas Disease: Results at 4-Year Follow-Up in a Prospective, Historically Controlled Study (CHICO SECURE).

Altcheh J, Sierra V, Ramirez T, Pinto Rocha J, Grossmann U, Huang E Antimicrob Agents Chemother. 2023; 67(4):e0119322.

PMID: 36975790 PMC: 10112190. DOI: 10.1128/aac.01193-22.

Modulation of STAT-1, STAT-3, and STAT-6 activities in THP-1 derived macrophages infected with two strains.

Oliveira M, Bonturi C, Salu B, Oliva M, Mortara R, Orikaza C Front Immunol. 2022; 13:1038332.

PMID: 36389843 PMC: 9643828. DOI: 10.3389/fimmu.2022.1038332.

SARS-CoV-2 Infection and CMV Dissemination in Transplant Recipients as a Treatment for Chagas Cardiomyopathy: A Case Report.

Gozzi-Silva S, Benard G, Alberca R, Yendo T, Emidio Teixeira F, Oliveira L Trop Med Infect Dis. 2021; 6(1).

PMID: 33579042 PMC: 7985779. DOI: 10.3390/tropicalmed6010022.

References

Talvani A, Rocha M, Barcelos L, Gomes Y, Ribeiro A, Teixeira M . Elevated concentrations of CCL2 and tumor necrosis factor-alpha in chagasic cardiomyopathy. Clin Infect Dis. 2004; 38(7):943-50. DOI: 10.1086/381892. View

Magdaleno A, Ahn I, Paes L, Silber A . Actions of a proline analogue, L-thiazolidine-4-carboxylic acid (T4C), on Trypanosoma cruzi. PLoS One. 2009; 4(2):e4534. PMC: 2645137. DOI: 10.1371/journal.pone.0004534. View

Almeida D, Carvalho A, Branco J, Pereira A, Correa L, Vianna P . Chagas' disease reactivation after heart transplantation: efficacy of allopurinol treatment. J Heart Lung Transplant. 1996; 15(10):988-92. View

Piaggio E, Roggero E, Pitashny M, Wietzerbin J, Bottasso O, Revelli S . Treatment with benznidazole and its immunomodulating effects on Trypanosoma cruzi-infected rats. Parasitol Res. 2001; 87(7):539-47. DOI: 10.1007/s004360000357. View

Bonney K, Engman D . Chagas heart disease pathogenesis: one mechanism or many?. Curr Mol Med. 2008; 8(6):510-8. PMC: 2859714. DOI: 10.2174/156652408785748004. View

Urbina J . Chemotherapy of Chagas' disease: the how and the why. J Mol Med (Berl). 1999; 77(3):332-8. DOI: 10.1007/s001090050359. View

Laucella S, Postan M, Martin D, Hubby Fralish B, Albareda M, Alvarez M . Frequency of interferon- gamma -producing T cells specific for Trypanosoma cruzi inversely correlates with disease severity in chronic human Chagas disease. J Infect Dis. 2004; 189(5):909-18. DOI: 10.1086/381682. View

Gattuso J, Kamm M . Review article: the management of constipation in adults. Aliment Pharmacol Ther. 1993; 7(5):487-500. DOI: 10.1111/j.1365-2036.1993.tb00124.x. View

Lages-Silva E, Filardi L, Brener Z . Effect of the host specific treatment in the phagocytosis of Trypanosoma cruzi blood forms by mouse peritoneal macrophages. Mem Inst Oswaldo Cruz. 1990; 85(4):401-5. DOI: 10.1590/s0074-02761990000400003. View

10.

Rivarola H, Paglini-Oliva P . Trypanosoma cruzi trypanothione reductase inhibitors: phenothiazines and related compounds modify experimental Chagas' disease evolution. Curr Drug Targets Cardiovasc Haematol Disord. 2003; 2(1):43-52. DOI: 10.2174/1568006023337745. View

11.

Tzelepis F, de Alencar B, Penido M, Gazzinelli R, Persechini P, Rodrigues M . Distinct kinetics of effector CD8+ cytotoxic T cells after infection with Trypanosoma cruzi in naive or vaccinated mice. Infect Immun. 2006; 74(4):2477-81. PMC: 1418894. DOI: 10.1128/IAI.74.4.2477-2481.2006. View

12.

Caldas I, Talvani A, Caldas S, Carneiro C, Lana M, da Matta Guedes P . Benznidazole therapy during acute phase of Chagas disease reduces parasite load but does not prevent chronic cardiac lesions. Parasitol Res. 2008; 103(2):413-21. DOI: 10.1007/s00436-008-0992-6. View

13.

Maya J, Cassels B, Iturriaga-Vasquez P, Ferreira J, Faundez M, Galanti N . Mode of action of natural and synthetic drugs against Trypanosoma cruzi and their interaction with the mammalian host. Comp Biochem Physiol A Mol Integr Physiol. 2006; 146(4):601-20. DOI: 10.1016/j.cbpa.2006.03.004. View

14.

Lages-Silva E, Ramirez L, Krettli A, Brener Z . Effect of protective and non-protective antibodies in the phagocytosis rate of Trypanosoma cruzi blood forms by mouse peritoneal macrophages. Parasite Immunol. 1987; 9(1):21-30. DOI: 10.1111/j.1365-3024.1987.tb00485.x. View

15.

Revelli S, Le Page C, Piaggio E, Wietzerbin J, Bottasso O . Benznidazole, a drug employed in the treatment of Chagas' disease, down-regulates the synthesis of nitrite and cytokines by murine stimulated macrophages. Clin Exp Immunol. 1999; 118(2):271-7. PMC: 1905429. DOI: 10.1046/j.1365-2249.1999.01053.x. View

16.

Higuchi M, Ries M, Aiello V, Benvenuti L, Gutierrez P, Bellotti G . Association of an increase in CD8+ T cells with the presence of Trypanosoma cruzi antigens in chronic, human, chagasic myocarditis. Am J Trop Med Hyg. 1997; 56(5):485-9. DOI: 10.4269/ajtmh.1997.56.485. View

17.

Frank F, Petray P, Cazorla S, Munoz M, Corral R, Malchiodi E . Use of a purified Trypanosoma cruzi antigen and CpG oligodeoxynucleotides for immunoprotection against a lethal challenge with trypomastigotes. Vaccine. 2003; 22(1):77-86. DOI: 10.1016/s0264-410x(03)00541-3. View

18.

Frank F, Cazorla S, Sartori M, Corral R . Elicitation of specific, Th1-biased immune response precludes skeletal muscle damage in cruzipain-vaccinated mice. Exp Mol Pathol. 2007; 84(1):64-70. DOI: 10.1016/j.yexmp.2007.10.004. View

19.

Engel J, Doyle P, Hsieh I, McKerrow J . Cysteine protease inhibitors cure an experimental Trypanosoma cruzi infection. J Exp Med. 1998; 188(4):725-34. PMC: 2213346. DOI: 10.1084/jem.188.4.725. View

20.

Kroll-Palhares K, Silverio J, da Silva A, Michailowsky V, Marino A, Silva N . TNF/TNFR1 signaling up-regulates CCR5 expression by CD8+ T lymphocytes and promotes heart tissue damage during Trypanosoma cruzi infection: beneficial effects of TNF-alpha blockade. Mem Inst Oswaldo Cruz. 2008; 103(4):375-85. DOI: 10.1590/s0074-02762008000400011. View