Browsing by Autor "Fernando Rosas"

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Chagasic Cardiomyopathy
(2012) Fernando Rosas; Nubia Roa; M. Zulma; Adriana Cullar; J Garcia Mario; J. Concepcin
T. cruzi exhibits a complex life cycle involving four well-defined developmental stages that interplay into two hosts, the blood-sucking insect vector, and the mammalian host (humans and animals). After already-infected insects feed on the mammalian host, they eliminate in their feces the metacyclic trypomastigotes (parasite infective form), which penetrate the body through the bite-wound, any damaged tissue, or the mucosa from eyes, nose, or even the digestive tract and invade host cells like fibroblasts, macrophages, and epithelial cells at the inoculation site. In the cytoplasm, free-parasites are differentiated into amastigotes (Fig. A B C Fig. 1. (A) Intracellular amastigotes of T. cruzi-infecting Vero cells, (B) Trypomastigotes, and (C) Epimastigotes stained with Giemsa.
Inhibitory Receptor Expression on CD8+ T Cells Is Linked to Functional Responses against <i>Trypanosoma cruzi</i> Antigens in Chronic Chagasic Patients
(American Association of Immunologists, 2015) Paola Lasso; Jose Mateus; Paula Pavía; Fernando Rosas; Nubia Roa; M. Carmen Thomas; Manuel Carlos López; John Mario González; Concepción J. Puerta; Adriana Cuéllar
In mammals, chronic diseases resulting from infectious agents have been associated with functional T cell response deficiency, a high frequency of terminally differentiated T cells, the presence of monofunctional Ag-specific T cells, and increased expression of inhibitory receptors. Similar to other chronic diseases, the progressive loss of certain functional activities during Trypanosoma cruzi infection might result in the inability to control replication of this parasite. To examine this hypothesis, we evaluated the differentiation and cell effector function of CD8(+) T cells and characterized the expression of inhibitory receptors and the presence of the parasite in the bloodstream of chagasic patients. The results showed that patients at an advanced severe disease stage had a higher frequency of terminally differentiated CD8(+) T cells than patients at an early stage of the disease. A monofunctional CD8(+) T cell response was observed in patients at an advanced stage, whereas the coexpression of markers that perform three and four functions in response to parasite Ags was observed in patients at a less severe disease stage. The frequency of CD8(+) T cells producing granzyme B and perforin and those expressing inhibitory receptors was higher in symptomatic patients than in asymptomatic patients. Taken together, these findings suggest that during the course of Chagas disease, CD8(+) T cells undergo a gradual loss of function characterized by impaired cytokine production, the presence of advanced differentiation, and increased inhibitory receptor coexpression.
Proliferative dysfunction in chronically activated T lymphocytes from chagasic patients (70.1)
(American Association of Immunologists, 2012) Nicolás A. Giraldo; Natalia I. Bolaños; Adriana Cuéllar; Nubia Roa; Zulma M. Cucunubá; Víctor Manuel Velasco; Fernando Rosas; Concepción J. Puerta; John Mario González
Abstract Background: Trypanosoma cruzi persistence has been associated with cardiac and gastrointestinal tissue damage in nearly 30% of the infected individuals; however, the pathogenic mechanisms are yet unknown. This study’s goal was to compare the activation status and proliferative capacity of T lymphocytes among chronic chagasic patients and uninfected controls. Methodology: Twenty-seven chronic chagasic patients, 20 healthy individuals and 28 non-chagasic cardiomyopathy donors were analyzed. Peripheral blood cells were stained with CD3, CD4, CD8, CD28, HLA-DR and CD38. PBMCs were labeled with CFSE and co-cultivated with PHA or T. cruzi lysate; at the fifth day post-stimulation cells were stained for CD3, CD4 and CD8. Results: Chagasic patients displayed higher frequencies of CD4+ (P=0.0001) and CD8+ (P=0.0002) T cells co-expressing HLA-DR and CD38 in comparison with healthy and non-chagasic cardiomyopathy donors. Also, the former group exhibited lower percentages of CD8+/CD28+ T lymphocytes (P=0.0005). After 5 days of stimulation, the proliferation index was lower in both CD4+ (P=0.01) and CD8+ (P=0.04) PHA-stimulated T cells from chagasic donors when compared with both control groups. Conclusions: Despite their increased activation status, the T lymphocytes from chagasic donors displayed reduced proliferative capacity after mitogenic stimulation, corroborating a dysfunctional cellular immune response in the chronic stages of the disease.
Randomized Trial of Benznidazole for Chronic Chagas’ Cardiomyopathy
(Massachusetts Medical Society, 2015) Carlos A. Morillo; José Antônio Marin‐Neto; Álvaro Avezum; Sergio Sosa‐Estáni; Anis Rassi; Fernando Rosas; Erick Villena; Roberto Quiroz; Rina Bonilla; Constança Britto
Trypanocidal therapy with benznidazole in patients with established Chagas' cardiomyopathy significantly reduced serum parasite detection but did not significantly reduce cardiac clinical deterioration through 5 years of follow-up. (Funded by the Population Health Research Institute and others; ClinicalTrials.gov number, NCT00123916; Current Controlled Trials number, ISRCTN13967269.).
The fraction of T. cruzi-antigen specific T cells in chronic chagasic patients detected by CD154 and membrane TNFα expression (MPF2P.802)
(American Association of Immunologists, 2014) Juan G. Ripoll; Nicolás A. Giraldo; Natalia I. Bolaños; Adriana Cuéllar; Nubia Roa; Fernando Rosas; Víctor Manuel Velasco; Zulma M. Cucunubá; Concepción J. Puerta; John Mario González
Abstract Background: Chagas disease is a chronic parasitic infection whose pathogenesis is related to parasite persistence and a dysfunctional cellular immune response. There is no method to determine the pool of antigen-specific T cells in Trypanosoma cruzi-infected patients. Thus, the goal of this work was to determine the fraction of antigen-specific T cells by measuring the expression of CD154 and membrane TNFα on the bulk of parasite-stimulated PBMCs. Methodology: Twenty-one chagasic patients (CP), 11 healthy controls (HC) and 5 non-chagasic individuals with chronic heart disease (NCC) were analyzed. PBMCs were incubated in the presence of anti-CD28, anti-CD49d, anti-TNFα and TACE inhibitor as follows: non stimulus, T. cruzi-lysate or SEB. Later, the samples were stained for CD3, CD4, CD8 and CD154 and analyzed by flow cytometry. Results: Symptomatic (3.07%, SD ±1.98) and asymptomatic CP (1.24 ±0.59) displayed higher frequencies of CD4+/CD154+ cells after incubation with T. cruzi-lysate in comparison with NCC (0.084 ±0.03) and HC (0.11 ±0.08) donors P&lt;0.0001. Likewise, the frequency of CD8+ cells expressing membrane TNFα with parasite stimulus was higher in symptomatic (3.76% ±1.43) and asymptomatic patients (2.22 ±0.53) compared with NCC (1.28 ±0.45) and HC (0.57 ±0.41) donors P&lt;0.0001. Conclusions: These results suggest that membrane TNFα and CD154 after stimulation with T. cruzi-lysate could be useful to determine the fraction of parasite-specific T cells.