A5024030442- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Immune Cell Function and Interaction
- Synthesis and Biological Evaluation
- Viral Infections and Immunology Research
- Eosinophilic Disorders and Syndromes
- Parasites and Host Interactions
- Cytomegalovirus and herpesvirus research
- Insect symbiosis and bacterial influences
- Galectins and Cancer Biology
- Complement system in diseases
- Lysosomal Storage Disorders Research
- Parasitic Infections and Diagnostics
- Cardiomyopathy and Myosin Studies
- Signaling Pathways in Disease
- Whipple's Disease and Interleukins
- T-cell and B-cell Immunology
- Biochemical and Molecular Research
- Toxin Mechanisms and Immunotoxins
- Helminth infection and control
Administración Nacional de Laboratorios e Institutos de Salud
2015-2024
Consejo Nacional de Investigaciones Científicas y Técnicas
2021-2023
Hospital General de Agudos Dr. TEODORO ALVAREZ
2013-2015
Institute of Parasitology
2009
Marine Biological Laboratory
2006
This study sought to quantify CD8(+) T cell responses Trypanosoma cruzi and identify potential links between these the severity of disease in humans. In majority patients with Chagas disease, staining class I major histocompatibility complex tetramers analysis interferon (IFN)- gamma ELISPOT a panel known cytotoxic lymphocyte target epitopes from T. failed parasite-specific cells. However, frequency individuals positive was higher areas active transmission. Analysis IFN- parasite lysate...
We present a cross-sectional analysis of the maturation and migratory properties memory CD8+ T cell compartment, in relation to severity heart disease individuals with chronic Trypanosoma cruzi infection removed from endemic areas for longer than 20 years. Subjects none or mild involvement were more likely mount T. cruzi-specific IFN-γ responses subjects advanced cardiac disease, population was enriched early-differentiated (CD27+CD28+) cells responding individuals. In contrast, frequency...
As many as 20 million people are living with Trypanosoma cruzi infection in Latin American, yet few receive any treatment. The major limitation developing and evaluating potential new drugs for their efficacy is the lack of reliable tests to assess parasite burden elimination.Adults volunteers chronic T. were evaluated clinically stratified according Kuschnir classification. Individuals group 0 1 clinical status treated benznidazole (5 mg/kg per day 30 days). changes cruzi-specific T cell...
Abstract Previously we found that the frequency of IFN-γ-producing CD8+ T cells specific for Trypanosoma cruzi inversely correlates with disease severity in chronic human Chagas along low levels IL-2-secreting all clinical stages. This impairment parasite-specific cell responses was associated phenotypic features immune senescence compartment. These data prompted us to address question whether CD4+ compartment also experiences signs exhaustion. Thus, performed a functional and phenotypical...
Previously, we identified a set of HLA-A020.1-restricted trans-sialidase peptides as targets CD8+ T cell responses in HLA-A0201+ individuals chronically infected by T. cruzi.Herein, report the identification encoded same gene family that bind alleles representative 6 most common class I HLA-supertypes. Based on combination bioinformatic predictions and HLA-supertype considerations, total 1001 epitopes predicted to HLA A01, A02, A03, A24, B7 B44 supertypes was selected. Ninety-six...
We had formerly demonstrated that subjects chronically infected with Trypanosoma cruzi show impaired T cell responses closely linked a process of exhaustion. Recently, the expression several inhibitory receptors has been associated dysfunction and In this study, we have examined cytotoxic lymphocyte antigen 4 (CTLA-4) leukocyte immunoglobulin like receptor 1 (LIR-1) by peripheral T. antigen-responsive IFN-gamma (IFN-γ)-producing total cells from cruzi-infected different clinical forms...
Even though the use of combined drugs has been proved to be effective in other chronic infections, assessment treatment antiparasitic human Chagas' disease not performed. Herein, a pilot study was conducted evaluate tolerance and side effects sequential two drugs, allopurinol benznidazole, phase Trypanosoma cruzi infection.Changes total T. cruzi-specific T B cells were monitored during median follow-up 36 months. Allopurinol administered for 3 months (600 mg/day) followed by 30 days...
Background Adults with chronic Trypanosoma cruzi exhibit a poorly functional T cell compartment, characterized by monofunctional (IFN-γ-only secreting) parasite-specific cells and increased levels of terminally differentiated cells. It is possible that persistent infection and/or sustained exposure to parasites antigens may lead progressive loss function the immune Methodology/Principal Findings To test this hypothesis, quality magnitude T. cruzi-specific responses were evaluated in...
Background. In contrast to adults, Trypanosoma cruzi-infected children have more broadly functional cruzi-specific T cells, and the total T-cell compartment exhibits fewer signs of immune exhaustion. However, not much is known about link between immunocompetence treatment efficacy for human Chagas disease. Methods. Using cytokine enzyme-linked immunosorbent spot (ELISPOT) polychromatic flow cytometry, cytometric bead assay, multiplex serological assays quantitative PCR, we evaluated T....
Abstract We have previously demonstrated that immune responses in subjects with chronic Trypanosoma cruzi infection display features common to other persistent infections signs of T cell exhaustion. Alterations cytokine receptor signal transduction emerged as one the cell-intrinsic mechanisms In this study, we performed an analysis expression IL-7R components (CD127 and CD132) on CD4+ CD8+ cells evaluated IL-7–dependent signaling events patients at different clinical stages chagasic heart...
Background Chagas disease is the highest impact parasitic in Latin America. We have proposed that changes Trypanosoma cruzi-specific immune responses might serve as surrogate indicators of treatment success. Herein, we addressed a long-term follow-up study whether cure achieved after can be predicted by non-conventional indexes anti-parasite serological and T cell activities. Methodology/Principal Findings T. responses, measured interferon-γ ELISPOT antibodies assessed ELISA,...
ABSTRACT The effect of interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ) on Trypanosoma cruzi multiplication nitric oxide (NO) production in cardiac myocytes was investigated. Cardiac myocyte cultures were obtained from neonatal Wistar rat hearts, infected with T. , treated IL-1β, TNF-α, IFN-γ, or N -monomethyl- l -arginine ( -NAME) for 72 h. Parasite growth calculated the number cells Giemsa-stained smears. Nitric determined Griess reagent. Inducible...
Allopurinol is the most popular commercially available xanthine oxidase inhibitor and it widely used for treatment of symptomatic hyperuricaemia, or gout. Although, several anti-inflammatory actions allopurinol have been demonstrated in vivo vitro, there few studies on action T cells. In current study, we assessed effect antigen-specific mitogen-driven activation cytokine production human markedly decreased frequency IFN-γ IL-2-producing cells, either after polyclonal stimulation with Herpes...
Background The severity of cardiac disease in chronic Chagas patients is associated with different features T-cell exhaustion. Here, we assessed whether the ability T cells to secrete IFN-γ response T. cruzi was linked disruption immune homeostasis and inflammation disease. Methodology/Principal findings PBMCs from uninfected controls were examined for frequencies cruzi-responsive IFN-γ-producing by ELISPOT cellular expression function IL-7R using flow cytometry. Serum levels IL-7, IL-21,...
Background. Subjects are considered infected with Trypanosoma cruzi when tested positive by at least two out of three serological tests, whereas a result in only one up to tests is termed "serodiscordant". Assessment parasite-specific T-cell responses, may help discriminate the uninfected from individuals among serodiscordant subjects. Methods. Peripheral blood mononuclear cells and seropositive subjects, who were born areas endemic for infection but living Buenos Aires city, Argentina, time...
We previously reported that the T cell compartment in chronically Trypanosoma cruzi- infected adult subjects display functional and phenotypic signs of immune senescence. This study aimed to investigate differentiation senescent profile overall CD8 + T. cruzi -infected children at early stage disease. found a lower percentage naive (CD27 CD28 CD45RA ) antigen-experienced (CD45RA − CD27 ), higher percentages late differentiated cells as compared with age-matched uninfected controls. The...
Background Chronic infection with Trypanosoma cruzi leads to a constant stimulation of the host immune system. Monocytes, which are recruited in response inflammatory signals, divided into classical CD14hiCD16—, non-classical CD14loCD16+ and intermediate CD14hiCD16+ subsets. In this study, we evaluated frequencies monocyte subsets different clinical stages chronic Chagas disease comparison profile seronegative heart failure subjects healthy controls. The effect anti-parasite drug therapy...
Abstract Background Interruption of benznidazole therapy due to the appearance adverse effects, which is presumed lead treatment failure, a major drawback in chronic Chagas disease. Methods Trypanosoma cruzi-specific humoral and T cell responses, phenotype parasite load were measured compare outcome 33 subjects with disease treated an incomplete regimen 58 complete regimen, during median follow-up period 48 months. Results Both regimens induced reduction T. antibody levels similar rates...
Chronic inflammation, as a consequence of the persistent infection with Trypanosoma cruzi, leads to continuous activation immune system in patients chronic Chagas disease. We have previously shown that increased sera levels soluble P-selectin are associated severity cardiomyopathy distinctive In this study, we explored expression biomarkers platelet and endothelial activation, tissue remodeling, mediators coagulation cascade at different clinical stages heart The frequencies activated...
Cyclophilins (CyPs) are a family of enzymes involved in protein folding. Trypanosoma cruzi, the causative agent Chagas disease, has 19-kDa cyclophilin, TcCyP19, that was found to be secreted parasite stages CL Brener clone and recognized by sera from T. cruzi-infected mice patients. The levels specific antibodies against TcCyP19 subjects before after drug treatment were measured an in-house enzyme linked immunosorbent assay (ELISA). Mice acute chronic phase infection, with successful...
A drawback in the treatment of chronic Chagas disease (American trypanosomiasis) is long time required to achieve complete loss serological reactivity, standard for determining efficacy.Antibody-secreting cells and memory B specific Trypanosoma cruzi their degree differentiation were evaluated adult pediatric study participants with before after etiological treatment.T. cruzi-specific antibody-secreting disappeared from circulation benznidazole or nifurtimox-treated declining...
In chronic Chagas disease, Trypanosoma cruzi -specific T-cell function decreases over time, and alterations in the homeostatic IL-7/IL-7R axis are evident, consistent with a process of immune exhaustion. IL-27 is an important immunoregulatory cytokine that shares signaling IL-7 other cytokines IL-12 family might be involved transcriptional regulation function. Here, we evaluated expression IL-27R antigen-experienced T cells from subjects disease assessed whether vitro treatment improve ....