Impact of Aetiological Treatment on Conventional and Multiplex Serology in Chronic Chagas Disease

The main criterion for treatment effectiveness in Chagas Disease has been the seronegative conversion of previously reactive serology, generally achieved many years post-treatment. The lack of reliable tests to ensure parasite clearance and to examine the effect of treatment is the main difficulty in evaluating treatment for chronic Chagas disease. Decreases of conventional and non-conventional serological titers can be useful tools to monitor the early impact of treatment. We serially measured changes in antibody levels, including seronegative conversion as well as declines in titers in 53 benznidazole-treated and 89 untreated chronically T. cruzi-infected subjects. Seronegative conversion as well as decreases of titers was significantly higher in treated compared with untreated patients. A strong concordance was found between decreases of titers of conventional and non-conventional serologic tests post-treatment, reaffirming the findings. When seronegative conversion plus decreases of titers were considered altogether, the impact of treatment was higher, in a shorter follow-up period than previously considered. New tools for monitoring the effectiveness of treatment of chronic Chagas disease are necessary, and the results showed in this study is a contribution to researchers and physicians who assist patients suffering from this disease

Sexual transmission of American trypanosomiasis in humans : a new potential pandemic route for Chagas parasites

Background: the Trypanosoma cruzi infection endemic in Latin America has now spread to several countries across four continents; this endemic involves triatomine vector-free protists. We hypothesised that the sexual transmission of T. cruzi contributes to the ongoing spread of Chagas disease. Objectives: a short-term longitudinal study was conducted to evaluate this hypothesis. Methods: the study population comprised 109 subjects from four families, among whom 21 had been diagnosed with acute Chagas disease by direct parasitological analysis. Blood mononuclear cells and serum samples were obtained from each study subject once per year for three consecutive years. Enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence serological examinations were used to detect specific T. cruzi antibodies. Polymerase chain reaction of T. cruzi DNA revealed 188-nucleotide bands, which hybridised to a specific radiolabelled probe and were confirmed by cloning and sequencing. Results: three independent assessments at different time points revealed T. cruzi nuclear DNA footprints in 76% (83/109) of the study population with active infection. In contrast, the ELISA and indirect immunofluorescence assays detected the T. cruzi antibody in 28.4% (31/109) of the study samples. Moreover, the semen from 82.6% (19/23) of subjects people revealed harboured the 188- bp base pair T. cruzi footprint. Interestingly, the ejaculates of nuclear DNA-positive Chagas patient transmitted the T. cruzi upon peritoneal injection or infusion in the vagina of mice, and amastigotes were detected in the skeletal muscle, myocardium, vas deferens, and uterine tube. Main conclusions: T. cruzi infections can be transmitted from females or males to naïve mates through intercourse, and progeny showed discrepancies between the ratios of nuclear DNA footprints and specific antibody that can be explained by the tolerance attained during early embryo growth. Additional studies are needed to develop drugs to eradicate the infections. Additionally, the importance of a vigorous education, information, and communication program to prevent sexually transmitted Chagas disease in humans cannot be underemphasised

Dendritic cells and parasites: from recognition and activation to immune response instruction

The effective defense against parasite infections requires the ability to mount an appropriate and controlled specific immune response able to eradicate the invading pathogen while limiting the collateral damage to self-tissues. Dendritic cells are key elements for the development of immunity against parasites; they control the responses required to eliminate these pathogens while maintaining host homeostasis. Ligation of dendritic cell pattern recognition receptors by pathogen-associated molecular pattern present in the parasites initiates signaling pathways that lead to the production of surface and secreted proteins that are required, together with the antigen, to induce an appropriate and timely regulated immune response. There is evidence showing that parasites can influence and regulate dendritic cell functions in order to promote a more permissive environment for their survival. In this review, we will focus on new insights about the ability of protozoan and helminth parasites or their products to modify dendritic cell function and discuss how this interaction is crucial in shaping the host response.Fil: Motran, Claudia Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Ambrosio, Laura Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Volpini, Ximena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Celias, Daiana Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Cervi, Laura Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentin

Chagasic patients are able to respond against a viral antigen from influenza virus

<p>Abstract</p> <p>Background</p> <p><it>Trypanosoma cruzi,</it> the etiological agent of Chagas’ disease<it>,</it> is an obligate intracellular parasite which induces a CD8⁺ T cell immune response with secretion of cytokines and release of cytotoxic granules. Although an immune-suppressive effect of <it>T. cruzi</it> on the acute phase of the disease has been described, little is known about the capacity of CD8⁺ T cell from chronic chagasic patients to respond to a non-<it>T. cruzi</it> microbial antigen.</p> <p>Methods</p> <p>In the present paper, the frequency, phenotype and the functional activity of the CD8⁺ T cells specific from Flu-MP*, an influenza virus epitope, were determined in 13 chagasic patients and 5 healthy donors.</p> <p>Results</p> <p>The results show that Flu-MP* peptide specific CD8⁺ T cells were found with similar frequencies in both groups. In addition, Flu-MP* specific CD8⁺ T cells were distributed in the early or intermediate/late differentiation stages without showing enrichment of a specific sub-population. The mentioned Flu-MP* specific CD8⁺ T cells from chagasic patients were predominately T_EM (CCR7- CD62L-), producing IL-2, IFNγ, CD107a/b and perforin, and did not present significant differences when compared with those from healthy donors.</p> <p>Conclusions</p> <p>Our results support the hypothesis that there is no CD8⁺ T cell nonspecific immune-suppression during chronic Chagas disease infection. Nonetheless, other viral antigens must be studied in order to confirm our findings.</p

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

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. cruzi infection, particularly in the context of cardiac pathology. We found that exposure of HL-1 cardiac cells to Gal-1 reduced the percentage of infection by two different T. cruzi strains, Tulahuén (TcVI) and Brazil (TcI). In addition, Gal-1 prevented exposure of phosphatidylserine and early events in the apoptotic program by parasite infection on HL-1 cells. These effects were not mediated by direct interaction with the parasite surface, suggesting that Gal-1 may act through binding to host cells. Moreover, we also observed that T. cruzi infection altered the glycophenotype of cardiac cells, reducing binding of exogenous Gal-1 to the cell surface. Consistent with these data, Gal-1 deficient (Lgals1-/-) mice showed increased parasitemia, reduced signs of inflammation in heart and skeletal muscle tissues, and lower survival rates as compared to wild-type (WT) mice in response to intraperitoneal infection with T. cruzi Tulahuén strain.CONCLUSION/SIGNIFICANCE:Our results indicate that Gal-1 modulates T. cruzi infection of cardiac cells, highlighting the relevance of galectins and their ligands as regulators of host-parasite interactions.Fil: Benatar, Alejandro Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; ArgentinaFil: Garcia, Gabriela Andrea. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Bua, Jacqueline Elena. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio E Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Postan, Miriam. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; ArgentinaFil: Tasso, Laura Mónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; ArgentinaFil: Scaglione, Jorge. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Pedro Elizalde" (ex Casa Cuna); ArgentinaFil: Stupirski, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Toscano, Marta Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Gomez, Karina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentin