-specific CD8 T cells and other immunological hallmarks in chronic Chagas cardiomyopathy: Two decades of research.

, the causal agent of Chagas disease, has coexisted with humans for thousands of years. Therefore, the parasite has developed several mechanisms of antigenic variability that has allowed it to live inside the cells and evade the host immune response. Since  displays an intracellular cycle-stage, our research team focused on providing insights into the CD8 T cells immune response in chronic Chagas cardiomyopathy.

False positive serology of prepandemic chagasic samples with SARS-CoV-2 antigen.

Objective: To determine whether prepandemic sera from patients with Chagas disease recognise SARS-CoV-2 antigens.

Materials And Methods: Forty sera from patients with Chagas disease were tested for the presence of IgG cross-reactivity against the nucleocapsid protein (NP) and spike (S) SARS-CoV-2 proteins by ELISA. Positive samples were tested again using a different ELISA and CLIA, both against NP.

A terpenoid-rich extract from exhibits anti- activity and induces T cell cytokine production.

Chagas disease, a worldwide public health concern, is a chronic infection caused by . Considering chronic persistence correlates with CD4 and CD8 T cell dysfunction and the safety and efficacy profiles of Benznidazol and Nifurtimox, the two drugs currently used for its etiological treatment, are far from ideal, the search of new trypanocidal treatment options is a highly relevant issue. Therefore, the objective of this work was to evaluate the trypanocidal effect and cytokine production induction of three extracts (hexane, dichloromethane and hydroalcoholic) obtained from , a plant traditionally used as a febrifuge in Colombia.

CD8 T Cell Response Quality Is Related to Parasite Control in an Animal Model of Single and Mixed Chronic Infections.

Chagas disease (ChD) is a chronic infection caused by . This highly diverse intracellular parasite is classified into seven genotypes or discrete typing units (DTUs) and they overlap in geographic ranges, vectors, and clinical characteristics. Although studies have suggested that ChD progression is due to a decline in the immune response quality, a direct relationship between T cell responses and disease outcome is still unclear.

Preliminary chemical characterization of ethanolic extracts from Colombian plants with promising anti - Trypanosoma cruzi activity.

Chagas disease is caused by Trypanosoma cruzi, and it is an important cause of morbidity and mortality in Latin America. There are no vaccines, and the chemotherapy available to treat this infection has serious side effects. In a search for alternative treatments, we determined the in vitro susceptibility of epimastigote and trypomastigote forms of T.

Diminished mitogen-induced T cell proliferation by Trypanosoma cruzi antigens associated with antigen-presenting cell modulation and CD3 signaling.

Chronic infection by Trypanosoma cruzi decreases T cell proliferation and it is most likely accompanied by changes in signals required for activation. We assessed the effect of T. cruzi antigens on mitogen-induced proliferation of T cells from uninfected individuals and the association with the expression of molecules involved in antigen presentation, T cell costimulation and activation, and cytokine production.

Intermediate Monocytes and Cytokine Production Associated With Severe Forms of Chagas Disease.

Monocytes are classified according to their CD14 and CD16 expression into classical (reparative), intermediate (inflammatory), and non-classical. This study assessed the frequency of monocyte and the relationship between monocyte subset percentages and the levels of blood cytokines in Colombian chagasic patients with different clinical forms. This study included chagasic patients in different clinical stages: indeterminate (IND) = 14, chronic chagasic cardiomyopathy (CCC) = 14, and heart transplant chagasic (HTCC) = 9; controls with non-chagasic cardiopathy (NCC) = 15, and healthy individuals (HI) = 15.

An Animal Model of Acute and Chronic Chagas Disease With the Reticulotropic Y Strain of That Depicts the Multifunctionality and Dysfunctionality of T Cells.

Chagas disease (ChD), a complex and persistent parasitosis caused by , represents a natural model of chronic infection, in which some people exhibit cardiac or digestive complications that can result in death 20-40 years after the initial infection. Nonetheless, due to unknown mechanisms, some -infected individuals remain asymptomatic throughout their lives. Actually, no vaccine is available to prevent ChD, and treatments for chronic ChD patients are controversial.

CD8 T Cell Response to Trypanosoma cruzi Antigens during Chronic Chagas Disease.

Flow cytometry is a valuable technique in cellular immunology that allows evaluating effective parameters of the immune response associated with CD8 T cells. During Chagas disease, infection caused by Trypanosoma cruzi parasite, similar to other intracellular infectious agents, antigen-specific CD8 T cells are essential for controlling the infection. However, CD8 T cell response is only partially effective in some chronic Chagas disease patients.

Impact of benznidazole treatment on the functional response of Trypanosoma cruzi antigen-specific CD4+CD8+ T cells in chronic Chagas disease patients.

Background: Chagas disease is caused by Trypanosoma cruzi. The persistence of the parasite is associated with the disease chronicity and the impairment of the cellular immune response. It has been reported that the CD4+CD8+ T cell population expands in chronic Chagas disease patients.

Detection in Colombian Patients with a Diagnosis of Esophageal Achalasia.

Achalasia is a motility disorder of the esophagus that might be secondary to a chronic infection. Several studies have investigated esophageal achalasia in patients with Chagas disease (CD) in Latin America, but no related studies have been performed in Colombia. The goals of the present study were to determine the presence of anti- antibodies in patients with esophageal achalasia who visited a referral hospital in Bogotá, Colombia, and to detect the presence of the parasite and its discrete typing units (DTUs).

T cells responding to Trypanosoma cruzi detected by membrane TNF-α and CD154 in chagasic patients.

Introduction: Chagas disease is a parasitic infection whose pathogenesis is related to parasite persistence and a dysfunctional cellular immune response. Variability in cytokine secretion among chronic Trypanosoma cruzi-infected patients might preclude the identification of the pool of antigen specific T cells. The goal of this study was to determine the fraction of T cells responding to T.

Expression of inhibitory receptors and polyfunctional responses of T cells are linked to the risk of congenital transmission of T. cruzi.

Congenital T. cruzi infections involve multiple factors in which complex interactions between the parasite and the immune system of pregnant women play important roles. In this study, we used an experimental murine model of chronic infection with T.

Antiparasitic Treatment Induces an Improved CD8 T Cell Response in Chronic Chagasic Patients.

Chagas disease is a chronic infection caused by an intracellular protozoan parasite. Chronic chagasic patients (CCPs) have dysfunctional CD8 T cells that are characterized by impaired cytokine production, high coexpression of inhibitory receptors, and advanced cellular differentiation. Most patients diagnosed in the chronic phase of Chagas disease already exhibit heart involvement, and there is no vaccination that protects against the disease.

Promiscuous Recognition of a Trypanosoma cruzi CD8+ T Cell Epitope among HLA-A2, HLA-A24 and HLA-A1 Supertypes in Chagasic Patients.

Background: TcTLE is a nonamer peptide from Trypanosoma cruzi KMP-11 protein that is conserved among different parasite strains and that is presented by different HLA-A molecules from the A2 supertype. Because peptides presented by several major histocompatibility complex (MHC) supertypes are potential targets for immunotherapy, the aim of this study was to determine whether MHC molecules other than the A2 supertype present the TcTLE peptide.

Methodology/principal Findings: From 36 HLA-A2-negative chagasic patients, the HLA-A genotypes of twenty-eight patients with CD8+ T cells that recognized the TcTLE peptide using tetramer (twenty) or functional (eight) assays, were determined.

Effect of secondary anchor amino acid substitutions on the immunogenic properties of an HLA-A*0201-restricted T cell epitope derived from the Trypanosoma cruzi KMP-11 protein.

The TcTLE peptide (TLEEFSAKL) is a CD8(+) T cell HLA-A*0201-restricted epitope derived from the Trypanosoma cruzi KMP-11 protein that is efficiently processed, presented and recognized by CD8(+) T cells from chagasic patients. Since the immunogenic properties of wild-type epitopes may be enhanced by suitable substitutions in secondary anchor residues, we have studied the effect of introducing specific mutations at position 3, 6 and 7 of the TcTLE peptide. Mutations (E3L, S6V and A7F) were chosen on the basis of in silico predictions and in vitro assays were performed to determine the TcTLE-modified peptide binding capacity to the HLA-A*0201 molecule.

Inhibitory Receptor Expression on CD8+ T Cells Is Linked to Functional Responses against Trypanosoma cruzi Antigens in Chronic Chagasic Patients.

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.

Altering the motility of Trypanosoma cruzi with rabbit polyclonal anti-peptide antibodies reduces infection to susceptible mammalian cells.

Trypanosoma cruzi's trypomastigotes are highly active and their incessant motility seems to be important for mammalian host cell infection. The kinetoplastid membrane protein-11 (KMP-11) is a protein expressed in all parasite stages, which induces a cellular and humoral immune response in the infected host, and is hypothesized to participate in the parasite's motility. An N-terminal peptide from KMP-11, termed K1 or TcTLE, induced polyclonal antibodies that inhibit parasitic invasion of Vero cells.

Low frequency of circulating CD8+ T stem cell memory cells in chronic chagasic patients with severe forms of the disease.

Background: CD8+ T cells have been shown to play a crucial role in Trypanosoma cruzi infection. Memory CD8+ T cells can be categorised based on their distinct differentiation stages and functional activities as follows: stem cell memory (TSCM), central memory (TCM), transitional memory (TTM), effector memory (TEM) and terminal effector (TTE) cells. Currently, the immune mechanisms that control T.

Mammalian cellular culture models of Trypanosoma cruzi infection: a review of the published literature.

Cellular culture infection with Trypanosoma cruzi is a tool used to dissect the biological mechanisms behind Chagas disease as well as to screen potential trypanocidal compounds. Data on these models are highly heterogeneous, which represents a challenge when attempting to compare different studies. The purpose of this review is to provide an overview of the cell culture infectivity assays performed to date.

[Preliminary evaluation of the commercial kit Chagas ( Trypanosoma cruzi ) IgG-ELISA ® in Colombian individuals].

Introduction: The diagnosis of Chagas' disease is essential to provide early treatment and improve patients' prognosis . The discriminatory efficiency of the serological tests varies according to the disease prevalence and the test- antigen used .

Objective: To evaluate the discriminatory efficiency of the commercial kit Chagas ( Trypanosoma cruzi ) IgG-ELISA ® (Nova Tec Immunodiagnostica GmbBH) in a group of Colombian individuals, using indirect immunofluorescence antibody testing (IFAT) and enzyme immunoassay (ELISA) tests as references.

[Design of a multicolor panel to assess intracellular and surface molecules by flow cytometry].

Introduction: Flow cytometry allows simultaneous detection of surface and intracellular molecules on each cell.

Objective: To describe a method for building up a harmonic multicolor panel with 11 flow cytometry parameters for phenotypic and functional analysis on CD8 + T lymphocytes.

Materials And Methods: For the multicolor panel construction, we selected the molecules and titred conjugated antibodies with fluorochromes for CD3, CD8, CCR7, CD28, CD27, CD45RA, CD95 and CD127 determination in peripheral blood mononuclear cells (PBMC).

Differences in IgE mediated basophil degranulation induced by proteic fractions from whole flea body extract in patients with papular urticaria by flea bite and healthy controls.

Background: Papular urticaria by flea bite (PUFB) is a chronic inflammatory disease in children. The aim of this study was to assess the functional activity of IgE to protein fractions from flea body extract, through basophil degranulation in PUFB patients and controls.

Methods: Basophil degranulation, measured by overexpression of CD63 surface molecules, was evaluated by flow cytometry in samples from patients and controls.

A human astrocytoma cell line is highly susceptible to infection with Trypanosoma cruzi.

Astrocytes play a vital role in neuronal protection, homeostasis, vascular interchange and the local immune response. Some viruses and parasites can cross the blood-brain barrier and infect glia. Trypanosoma cruzi, the aetiological agent of Chagas disease, can seriously compromise the central nervous system, mainly in immune-suppressed individuals, but also during the acute phase of the infection.

T lymphocytes from chagasic patients are activated but lack proliferative capacity and down-regulate CD28 and CD3ζ.

Background: Chronic persistent infections have been associated with T lymphocytes functional impairment. The aim of this study was to compare the activation status, the proliferative potential and the expression of CD28 and CD3ζ chain on T lymphocytes between chronic chagasic patients and uninfected controls.

Methodology/principal Findings: Forty-two chronic chagasic patients, 28 healthy individuals and 32 non-chagasic cardiomyopathy donors were included.