Vaccination with parasite-specific TcTASV proteins combined with recombinant baculovirus as a delivery platform protects against acute and chronic infection.

Chagas' is a neglected disease caused by the eukaryotic kinetoplastid parasite, Currently, approximately 8 million people are infected worldwide, most of whom are in the chronic phase of the disease, which involves cardiac, digestive, or neurologic manifestations. There is an urgent need for a vaccine because treatments are only effective in the initial phase of infection, which is generally underdiagnosed. The selection and combination of antigens, adjuvants, and delivery platforms for vaccine formulations should be designed to trigger mixed humoral and cellular immune responses, considering that has a complex life cycle with both intracellular and bloodstream circulating parasite stages in vertebrate hosts.

Importance of CD40/CD40 dyad in the course of infection with Trypanosoma cruzi: Impact of its inhibition.

Chagas heart disease (CHD), caused by the protozoan parasite Trypanosoma cruzi, consists of a progressive myocarditis which may lead to congestive heart failure or sudden death. Previous work from our laboratory has demonstrated that the experimental infection of mice with T. cruzi positively modulates the expression of CD40 by myocardial cells, whose ligation potentiates IFN-γ-induced IL-6 production.

Trypanosoma cruzi infection in Cyclophilin D deficient mice.

Trypanosoma cruzi is the causative agent of Chagas disease, which is endemic in Latin America and around the world through mother to child transmission. The heart is the organ most frequently affected in the chronic stage of the human infection and depends on mitochondria for the required energy for its activity. Cyclophilins are involved in protein folding and the mitochondrial isoform, Cyclophilin D (CyPD), has a crucial role in the opening of the mitochondrial permeability transition pore.

Anti-inflammatory Role of Galectin-8 During Chronic Infection.

Galectins are animal lectins with high affinity for β-galactosides that drive the immune response through several mechanisms. In particular, the role of galectin-8 (Gal-8) in inflammation remains controversial. To analyze its role in a chronic inflammatory environment, we studied a murine model of infection.

Circulating T Follicular Helper Cell Abnormalities Associated to Different Clinical Forms of Chronic Chagas Disease.

Multiple perturbations of the immune response affecting a range of cells have been reported in -infected individuals and associated to clinical manifestations of chronic Chagas disease. There is a paucity of knowledge about the role of T follicular helper (Tfh) cells in this infection. Here, we sought to characterize circulating Tfh (cTfh) cells in chronic Chagas disease patients and to identify potential associations with disease severity in humans.

Monocyte glycolysis determines CD8+ T cell functionality in human Chagas disease.

Chagas disease is a lifelong pathology resulting from Trypanosoma cruzi infection. It represents one of the most frequent causes of heart failure and sudden death in Latin America. Herein, we provide evidence that aerobic glycolytic pathway activation in monocytes drives nitric oxide (NO) production, triggering tyrosine nitration (TN) on CD8+ T cells and dysfunction in patients with chronic Chagas disease.

Phenotypic diversity and drug susceptibility of Trypanosoma cruzi TcV clinical isolates.

Trypanosoma cruzi is a genetically heterogeneous group of organisms that cause Chagas disease. It has been long suspected that the clinical outcome of the disease and response to therapeutic agents are, at least in part, related to the genetic characteristics of the parasite. Herein, we sought to validate the significance of the genotype of T.

Inactive -Sialidase Expression in Generates Virulent Trypomastigotes.

Disclosing virulence factors from pathogens is required to better understand the pathogenic mechanisms involved in their interaction with the host. In the case of several molecules are associated with virulence. Among them, the -sialidase (TS) has arisen as one of particular relevance due to its effect on the immune system and involvement in the interaction/invasion of the host cells.

Trypanosoma cruzi infection induces the expression of CD40 in murine cardiomyocytes favoring CD40 ligation-dependent production of cardiopathogenic IL-6.

The inflammatory response in the myocardium is an important aspect of the pathogenesis of Chagas' heart disease raised by Trypanosoma cruzi. CD40, a transmembrane type I receptor belonging to the tumor necrosis factor receptor (TNFR) family, is expressed in a broad spectrum of cell types and is crucial in several inflammatory and autoimmune diseases. Activation of CD40 through ligation to CD40L (CD154) induces multiple effects, including the secretion of proinflammatory molecules.

Galectin-1 Prevents Infection and Damage Induced by Trypanosoma cruzi on Cardiac Cells.

Background: Chronic Chagas cardiomyopathy caused by Trypanosoma cruzi is the result of a pathologic process starting during the acute phase of parasite infection. Among different factors, the specific recognition of glycan structures by glycan-binding proteins from the parasite or from the mammalian host cells may play a critical role in the evolution of the infection.

Methodology And Principal Findings: Here we investigated the contribution of galectin-1 (Gal-1), an endogenous glycan-binding protein abundantly expressed in human and mouse heart, to the pathophysiology of T.

Effects of artesunate against Trypanosma cruzi.

Therapy against Trypanosma cruzi relies on only two chemically related nitro-derivative drugs, benznidazole and nifurtimox, both limited by poor efficacy and toxicity. It is suspected that with prolonged usage of these drugs, resistant parasites will be selected, which results in risk for treatment failure over the time. Herein, we studied the in vitro activity of artesunate, the most effective drug to treat severe P.

Oxidative stress damage in the protozoan parasite Trypanosoma cruzi is inhibited by Cyclosporin A.

Cyclosporin A (CsA) specifically inhibits the mitochondrial permeability transition pore (mPTP). Opening of the mPTP, which is triggered by high levels of matrix [Ca2+] and/or oxidative stress, leads to mitochondrial dysfunction and thus to cell death by either apoptosis or necrosis. In the present study, we analysed the response of Trypanosoma cruzi epimastigote parasites to oxidative stress with 5 mm H2O2, by studying several features related to programmed cell death and the effects of pre-incubation with 1 μ m of CsA.

Altered distribution of peripheral blood memory B cells in humans chronically infected with Trypanosoma cruzi.

Numerous abnormalities of the peripheral blood T cell compartment have been reported in human chronic Trypanosoma cruzi infection and related to prolonged antigenic stimulation by persisting parasites. Herein, we measured circulating lymphocytes of various phenotypes based on the differential expression of CD19, CD4, CD27, CD10, IgD, IgM, IgG and CD138 in a total of 48 T. cruzi-infected individuals and 24 healthy controls.

Granulocyte colony-stimulating factor partially repairs the damage provoked by Trypanosoma cruzi in murine myocardium.

Background: The hallmark of Trypanosoma cruzi infection is cardiomyopathy that leads to end-stage heart failure. We investigated whether G-CSF, known to induce heart tissue repair by bone marrow stem cell mobilization, ameliorates T. cruzi-induced myocarditis.

Elevated serum levels of macrophage migration inhibitory factor are associated with progressive chronic cardiomyopathy in patients with Chagas disease.

Clinical symptoms of chronic Chagas disease occur in around 30% of the individuals infected with Trypanosoma cruzi and are characterized by heart inflammation and dysfunction. The pathogenesis of chronic chagasic cardiomyopathy (CCC) is not completely understood yet, partially because disease evolution depends on complex host-parasite interactions. Macrophage migration inhibitory factor (MIF) is a pleiotropic proinflammatory cytokine that promotes numerous pathophysiological processes.

Immunomodulatory and anti-fibrotic effects of ganglioside therapy on the cardiac chronic form of experimental Trypanosoma cruzi infection.

Heart failure and sudden death are the most common causes of death in patients with Chagas' disease. The main drug available for Chagas treatment is benznidazole, which eradicates Trypanosoma cruzi parasites during the acute stage of infection. However, its effectiveness during the chronic phase remains unclear.

Trypanosoma cruzi: biological characterization of a isolate from an endemic area and its susceptibility to conventional drugs.

We describe some biological and molecular characteristics of a Trypanosoma cruzi isolate derived from a Triatomine captured in Nicaragua. PCR based typification showed that this isolate, named Nicaragua, belonged to the lineage Tc I. Nicaragua infected culture cells were treated with allopurinol, showing different behavior according to the cellular compartment, being cardiomyocyte primary cultures more resistant to this drug.

Assessment of CD8(+) T cell differentiation in Trypanosoma cruzi-infected children.

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 the differentiation and the senescent profile of the overall CD8(+) T cell compartment in T. cruzi-infected children at the early stage of the disease.

Trypanosoma cruzi-specific immune responses in subjects from endemic areas of Chagas disease of Argentina.

Trypanosoma cruzi-specific immune responses were evaluated in a total of 88 subjects living in areas endemic of Chagas disease of Argentina by IFN-gamma ELISPOT assays and immunoblotting. Positive T. cruzi antigen-induced IFN-gamma responses were detected in 42% of subjects evaluated (15/26 positive by conventional serology and 22/62 seronegative subjects).

Changes in Trypanosoma cruzi-specific immune responses after treatment: surrogate markers of treatment efficacy.

Background: As many as 20 million people are living with Trypanosoma cruzi infection in Latin American, yet few receive any treatment. The major limitation in developing and evaluating potential new drugs for their efficacy is the lack of reliable tests to assess parasite burden and elimination.

Methods: Adults volunteers with chronic T.

Chronic human infection with Trypanosoma cruzi drives CD4+ T cells to immune senescence.

Previously we found that the frequency of IFN-gamma-producing CD8(+) T cells specific for Trypanosoma cruzi inversely correlates with disease severity in chronic human Chagas disease along with low levels of IL-2-secreting CD8(+) T cells in all clinical stages. This impairment of the parasite-specific T cell responses was associated with phenotypic features of immune senescence of the CD8(+) T cell compartment. These data prompted us to address the question of whether the CD4(+) T cell compartment also experiences signs of exhaustion.

Timing of expression of inflammatory mediators in skeletal muscles from mice acutely infected with the RA strain of Trypanosoma cruzi.

Objective: Chagas' disease is caused by persistent Trypanosoma cruzi infection in muscle cells that ultimately results in chronic inflammation and tissue destruction. The goal of this study was to determine the expression of different chemokines and their receptors, as well as proinflammatory cytokines and inducible nitric oxide synthase, in muscles from mice acutely infected with T. cruzi.

Identification of novel vaccine candidates for Chagas' disease by immunization with sequential fractions of a trypomastigote cDNA expression library.

The protozoan Trypanosoma cruzi is the etiological agent of Chagas' disease, a major chronic infection in Latin America. Currently, there are neither effective drugs nor vaccines for the treatment or prevention of the disease. Several T.