Differential phenotypic and functional profile of epitope-specific cytotoxic CD8+ T cells in benznidazole-treated chronic asymptomatic Chagas disease patients

Publication date: Available online 6 December 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Adriana Egui, Manuel Carlos López, Inmaculada Gómez, Marina Simón, Manuel Segovia, M. Carmen ThomasAbstractOne of the greatest challenges in Chagas disease research is the search for tools that will enable the assessment of pharmacological treatment efficacy. A recently described set of serological biomarkers composed of four parasite antigens and established criteria of treatment efficacy allowed the evaluation of the impact of benznidazole treatment a short/medium time after the treatment. In addition, cellular immunological parameters have also been described as potential indicators of the treatment response. The cytotoxic CD8+ T cells specific to five epitopes in the PFR2, PFR3, TcCA-2 and KMP11 antigens have been analysed, and these epitopes have been shown to be recognized, processed and presented in the context of a natural T. cruzi infection. In the present manuscript, we characterized these antigen-specific CD8+ T cells in indeterminate chronic Chagas disease patients both before and after (from 11 to 28 months) benznidazole treatment. The results indicate that there is a differential memory CD8+ T cell profile depending on the antigenic epitope and that the benznidazole treatment modulates the memory, differentiation and senescence phenotypes of the epitope-specific CD8+ T cells. Moreover, in these patients, the ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research

Related Links:

The etiological agent of Chagas disease, Trypanosoma cruzi, is an obligate intracellular parasite that infects an estimated 7 million people in the Americas, with an at-risk population of 70 million. Despite its recognition as the highest impact parasitic infection of the Americas, Chagas disease continues to receive insufficient attention and resources in order to be effectively combatted. Unlike the other parasitic trypanosomatids that infect humans (Trypanosoma brucei and Leishmania spp.), T. cruzi retains an ancestral mode of phagotrophic feeding via an endocytic organelle known as the cytostome-cytopharynx complex (SP...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
Authors: Norman FF, Comeche B, Chamorro S, López-Vélez R Abstract Introduction: Recent increases in population movements have created novel health challenges in many areas of the World, and health policies have been adapted accordingly in several countries. However, screening guidelines for infectious diseases are not standardized and generally do not include comprehensive screening for parasitic infections.Areas covered: Malaria, Chagas disease, leishmaniasis, amebiasis, filariases, strongyloidiasis and schistosomiasis are reviewed, focusing on the challenges posed for their diagnosis and management ...
Source: Expert Review of Anti-Infective Therapy - Category: Infectious Diseases Tags: Expert Rev Anti Infect Ther Source Type: research
Chagas disease is caused by Trypanosoma cruzi infection and represents an important public health concern in Latin America. Macrophages are one of the main infiltrating leukocytes in response to infection. Parasite persistence could trigger a sustained activation of these cells, contributing to the damage observed in this pathology, particularly in the heart. HP24, a pyridinecarboxylic acid derivative, is a new PPARγ ligand that exerts anti-inflammatory and pro-angiogenic effects. The aim of this work was to deepen the study of the mechanisms involved in the pro-angiogenic and anti-inflammatory effects of HP24 in T. ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
It is well-established that infectious stress activates the hypothalamus–pituitary–adrenal axis leading to the production of pituitary adrenocorticotropin (ACTH) and adrenal glucocorticoids (GCs). Usually, GC synthesis is mediated by protein kinase A (PKA) signaling pathway triggered by ACTH. We previously demonstrated that acute murine Chagas disease courses with a marked increase of GC, with some data suggesting that GC synthesis may be ACTH-dissociated in the late phase of this parasitic infection. Alternative pathways of GC synthesis have been reported in sepsis or mental diseases, in which interleukin (IL)...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
Trypanosoma is a genus of single-cell eukaryote organisms—parasites living in the bloodstream (or sometimes inside cells) of humans or other mammals and causing a number of serious diseases (such as Leishmaniasis, African trypanosomiasis [sleeping sickness], American trypanosomiasis [Chagas disease], and others). In most cases, they are transmitted by blood-feeding invertebrates,...
Source: Proceedings of the National Academy of Sciences - Category: Science Authors: Tags: Commentaries Source Type: research
In this study, we used a phage display approach to identify peptides from one library-LX8CX8 (17 aa) (where X corresponds to any amino acid). After testing different biopanning conditions using live or fixed epimastigotes, 10 clones were sequenced that encoded the same peptide, named here as EPI18. The bacteriophage expressing EPI18 binds to epimastigotes from distinct strains of T. cruzi. To confirm these results, this peptide was synthetized, biotinylated, and assayed using flow cytometry and confocal microscopy analyses. These assays confirmed the specificity of the binding capacity of EPI18 toward epimastigote surfaces...
Source: Experimental Parasitology - Category: Parasitology Authors: Tags: Exp Parasitol Source Type: research
Publication date: Available online 3 January 2020Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Augusto E. Bivona, Andrés Sánchez Alberti, Natacha Cerny, Sebastián N. Trinitario, Emilio L. MalchiodiAbstractChagas disease is currently endemic to 21 Latin-American countries and has also become a global concern because of globalization and mass migration of chronically infected individuals. Prophylactic and therapeutic vaccination might contribute to control the infection and the pathology, as complement of other strategies such as vector control and chemotherapy. Ideal...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research
by Marcia C. Paes, Francis M. S. Saraiva, Nat ália P. Nogueira, Carolina S. D. Vieira, Felipe A. Dias, Ana Rossini, Vitor Lima Coelho, Attilio Pane, Fei Sang, Marcos Alcocer Chagas disease, also known as American trypanosomiasis, is a potentially life-threatening illness caused by the protozoan parasite,Trypanosoma cruzi, and is transmitted by triatomine insects during its blood meal. Proliferative epimastigotes forms thrive inside the insects in the presence of heme (iron protoporphyrin IX), an abundant product of blood digestion, however little is known about the metabolic outcome of this signaling molecule in th...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
Cardiac Chagas Disease: MMPs, TIMPs, Galectins, and TGF-β as Tissue Remodelling Players. Dis Markers. 2019;2019:3632906 Authors: da Costa AWF, do Carmo Neto JR, Braga YLL, Silva BA, Lamounier AB, Silva BO, Dos Reis MA, de Oliveira FA, Celes MRN, Machado JR Abstract A century after the discovery of Chagas disease, studies are still needed to establish the complex pathophysiology of this disease. However, it is known that several proteins and molecules are related to the establishment of this disease, its evolution, and the appearance of its different clinical forms. Metalloproteinases and their tis...
Source: Disease Markers - Category: Laboratory Medicine Tags: Dis Markers Source Type: research
buquerque S Abstract Chagas disease is a tropical illness caused by the protozoan Trypanosoma cruzi. The disease affects populations of the Americas and has been spread to other continents due to the migration process. The disease is partially controlled by two drugs, Benznidazole and Nifurtimox. These molecules are active in the acute phase of the infection but are usually ineffective during the symptomatic chronic phase. Several research groups have developed novel candidates to control Chagas disease; however, no novel commercial formulation is available. In this article, we described the anti-T. cruzi effects ...
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
More News: Allergy & Immunology | Chagas Disease | Molecular Biology | Parasitic Diseases | Parasitology