Abstract
The aim of this review is to describe the contributions of the knowledge of T-cell responses to the understanding of the physiopathology and the responsiveness to etiological treatment during the chronic phase of Chagas disease. T-helper (Th)1 and interleukin (IL)-10 Trypanosoma cruzi-specific T-cells have been linked to the asymptomatic phase or to severe clinical forms of the disease, respectively or vice versa, depending on the T. cruzi antigen source, the patient’s location and the performed immunological assays. Parasite-specific T-cell responses are modulated after benznidazole (BZ) treatment in chronically T. cruzi-infected subjects in association with a significant decrease in T. cruzi-specific antibodies. Accumulating evidence has indicated that treatment efficacy during experimental infection with T. cruzi results from the combined action of BZ and the activation of appropriate immune responses in the host. However, strong support of this interaction in T. cruzi-infected humans remains lacking. Overall, the quality of T-cell responses might be a key factor in not only disease evolution, but also chemotherapy responsiveness. Immunological parameters are potential indicators of treatment response regardless of achievement of cure. Providing tools to monitor and provide early predictions of treatment success will allow the development of new therapeutic options.
Highlights
The aim of this review is to describe the contributions of the knowledge of T-cell responses to the understanding of the physiopathology and the responsiveness to etiological treatment during the chronic phase of Chagas disease
An emerging consensus has indicated that the persistence of parasites might lead to immune exhaustion and altered host immunoregulation, which might be responsible for cumulative tissue damage in chronic Chagas disease (Tarleton 2003, Laucella et al 2004, Albareda et al 2006, Gutierrez et al 2009)
We review the contributions of the knowledge of T-cell responses to the understanding of how treatment works with the aim of providing new tools to monitor and predict treatment success during the chronic phase of T. cruzi infection
Summary
Trypanosoma cruzi-specific T-cell responses in children and adults with Chagas disease living in nonendemic areas of Argentina measured by interferon (IFN)-γ and interleukin (IL)-2 ELISPOT. A: Fisher exact test p = 0.0181 vs percentage of IFN-γ-only responders in T. cruzi-infected children; b: p < 0.02 vs percentage of IFN-γ + IL-2 in adults; c: p < 0.05 vs percentage of IFN-γ-only in adults. Phenotypic characterization of Trypanosma cruzi-specif CD4+ T-cells in chronically infected subjects. Cruited for T-cell responses in chronically infected subjects. Long-term infection with T. cruzi results in the up-regulation of cytotoxic T lymphocyte antigen-4 (Figure) (Argüello et al 2012) likely as part of a homeostatic process to control tissue damage, this up-regulation might damper T-cell responses. The above-described findings are compatible with immune exhaustion, which has described for other chronic parasitic and viral infections (Gigley et al 2012, Rodrigues et al 2014)
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