Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 5 de 5
Filter
Add more filters










Database
Language
Publication year range
1.
Sci Rep ; 10(1): 1378, 2020 Jan 28.
Article in English | MEDLINE | ID: mdl-31992777

ABSTRACT

Previous work showed that the thymus can be infected by RNA viruses as HIV and HTLV-1. We thus hypothesized that the thymus might also be infected by the Zika virus (ZIKV). Herein we provide compelling evidence that ZIKV targets human thymic epithelial cells (TEC) in vivo and in vitro. ZIKV-infection enhances keratinization of TEC, with a decrease in proliferation and increase in cell death. Moreover, ZIKV modulates a high amount of coding RNAs with upregulation of genes related to cell adhesion and migration, as well as non-coding genes including miRNAs, circRNAs and lncRNAs. Moreover, we observed enhanced attachment of lymphoblastic T-cells to infected TEC, as well as virus transfer to those cells. Lastly, alterations in thymuses from babies congenitally infected were seen, with the presence of viral envelope protein in TEC. Taken together, our data reveals that the thymus, particularly the thymic epithelium, is a target for the ZIKV with changes in the expression of molecules that are relevant for interactions with developing thymocytes.


Subject(s)
Epithelial Cells , Thymocytes , Thymus Gland , Viral Tropism , Zika Virus Infection , Zika Virus/physiology , Animals , Chlorocebus aethiops , Epithelial Cells/metabolism , Epithelial Cells/pathology , Epithelial Cells/virology , Epithelium/metabolism , Epithelium/pathology , Epithelium/virology , Humans , Thymocytes/metabolism , Thymocytes/pathology , Thymocytes/virology , Thymus Gland/metabolism , Thymus Gland/pathology , Thymus Gland/virology , Vero Cells , Zika Virus Infection/metabolism , Zika Virus Infection/pathology
2.
PLoS One ; 13(9): e0203462, 2018.
Article in English | MEDLINE | ID: mdl-30183775

ABSTRACT

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. cruzi isolates recovered from patients with different clinical forms of Chagas disease living in Argentina on their biological behaviour and susceptibility to drugs. Genotype identification of the newly established isolates confirmed the reported predominance of TcV, with a minor frequency of TcI. Epimastigote sensitivity assays demonstrated marked dissimilar responses to benznidazole, nifurtimox, pentamidine and dihydroartemisinin in vitro. Two TcV isolates exhibiting divergent response to benznidazole in epimastigote assays were further tested for the expression of anti-oxidant proteins. Benznidazole-resistant BOL-FC10A epimastigotes had decreased expression of Old Yellow Enzyme and cytosolic superoxide dismutase, and overexpression of mitochondrial superoxide dismutase and tryparedoxin- 1, compared to benznidazole-susceptible AR-SE23C parasites. Drug sensitivity assays on intracellular amastigotes and trypomastigotes reproduced the higher susceptibility of AR-SE23C over BOL-FC10A parasites to benznidazole observed in epimastigotes assays. However, the susceptibility/resistance profile of amastigotes and trypomastigotes to nifurtimox, pentamidine and dihydroartemisinin varied markedly with respect to that of epimastigotes. C3H/He mice infected with AR-SE23C trypomastigotes had higher levels of parasitemia and mortality rate during the acute phase of infection compared to mice infected with BOL-FC10A trypomastigotes. Treatment of infected mice with benznidazole or nifurtimox was efficient to reduce patent parasitemia induced by either isolate. Nevertheless, qPCR performed at 70 dpi revealed parasite DNA in the blood of mice infected with AR-SE23C but not in BOL-FC10A infected mice. These results demonstrate high level of intra-type diversity which may represent an important obstacle for the testing of chemotherapeutic agents.


Subject(s)
Chagas Disease/metabolism , Drug Resistance/drug effects , Genotype , Phenotype , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/metabolism , Adult , Animals , Argentina , Chagas Disease/drug therapy , Chagas Disease/genetics , Chlorocebus aethiops , Female , Humans , Male , Mice , Middle Aged , Protozoan Proteins/genetics , Protozoan Proteins/metabolism , Trypanosoma cruzi/genetics , Vero Cells
3.
PLoS One ; 9(8): e104951, 2014.
Article in English | MEDLINE | ID: mdl-25111833

ABSTRACT

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. Infected individuals had decreased frequencies of CD19+CD27+ cells, which positively correlated with the frequencies of CD4+CD27+ cells. The contraction of CD19+CD27+ cells was comprised of IgG+IgD-, IgM+IgD- and isotype switched IgM-IgD- memory B cells, CD19+CD10+CD27+ B cell precursors and terminally differentiated CD19+CD27+CD138+ plasma cells. Conversely, infected individuals had increased proportions of CD19+IgG+CD27-IgD- memory and CD19+IgM+CD27-IgD+ transitional/naïve B cells. These observations prompted us to assess soluble CD27, a molecule generated by the cleavage of membrane-bound CD27 and used to monitor systemic immune activation. Elevated levels of serum soluble CD27 were observed in infected individuals with Chagas cardiomyopathy, indicating its potentiality as an immunological marker for disease progression in endemic areas. In conclusion, our results demonstrate that chronic T. cruzi infection alters the distribution of various peripheral blood B cell subsets, probably related to the CD4+ T cell deregulation process provoked by the parasite in humans.


Subject(s)
Antibodies, Protozoan/blood , Antigens, CD/blood , B-Lymphocyte Subsets/immunology , Chagas Disease/immunology , Immunologic Memory/immunology , Antigens, CD/biosynthesis , B-Lymphocyte Subsets/cytology , CD4-Positive T-Lymphocytes/immunology , Chagas Disease/parasitology , Chronic Disease , Humans , Immunoglobulin D/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Immunophenotyping , Plasma Cells/immunology , Precursor Cells, B-Lymphoid/immunology , Trypanosoma cruzi/immunology
4.
PLoS One ; 8(2): e57181, 2013.
Article in English | MEDLINE | ID: mdl-23451183

ABSTRACT

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. In the current study, we investigated the link between MIF and CCC progression.Immunohistochemical analysis demonstrated MIF overexpression in the hearts from chronically T. cruzi-infected mice, particularly those showing intense inflammatory infiltration. We also found that MIF exogenously added to parasite-infected murine macrophage cultures is capable of enhancing the production of TNF-α and reactive oxygen species, both with pathogenic roles in CCC. Thus, the integrated action of MIF and other cytokines and chemokines may account for leukocyte influx to the infected myocardium, accompanied by enhanced local production of multiple inflammatory mediators. We further examined by ELISA the level of MIF in the sera from chronic indeterminate and cardiomyopathic chagasic patients, and healthy subjects. CCC patients displayed significantly higher MIF concentrations than those recorded in asymptomatic T. cruzi-infected and uninfected individuals. Interestingly, increased MIF levels were associated with severe progressive Chagas heart disease, in correlation with elevated serum concentration of high sensitivity C-reactive protein and also with several echocardiographic indicators of left ventricular dysfunction, one of the hallmarks of CCC. Our present findings represent the first evidence that enhanced MIF production is associated with progressive cardiac impairment in chronic human infection with T. cruzi, strengthening the relationship between inflammatory response and parasite-driven pathology. These observations contribute to unravel the elements involved in the pathogenesis of CCC and may also be helpful for the design of novel therapies aimed to control long-term morbidity in chagasic patients.


Subject(s)
Cardiomyopathies/blood , Chagas Disease/blood , Macrophage Migration-Inhibitory Factors/blood , Animals , Cardiomyopathies/complications , Cardiomyopathies/pathology , Cell Line , Chagas Disease/complications , Chronic Disease , Disease Progression , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Humans , Immunohistochemistry , Macrophages/metabolism , Mice , Mice, Inbred C3H , Middle Aged , Reactive Oxygen Species/metabolism , Tumor Necrosis Factor-alpha/metabolism
5.
Exp Parasitol ; 126(2): 239-44, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20493848

ABSTRACT

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. The course of the infection in a mice experimental model and its susceptibility to benznidazole and allopurinol was analyzed. In benznidazole treatment, mice reverted the high lethal effect of parasites during the acute infection, however, a few parasites were detected in the heart of 88% of mice 1 year post-infection. Since T. cruzi is a heterogeneous species population it is important to study and characterize different parasites actually circulating in humans in endemic areas. In this work we show that T. cruzi Nicaragua isolate, is sensitive to early benznidazole treatment.


Subject(s)
Chagas Disease/epidemiology , Chagas Disease/parasitology , Endemic Diseases , Trypanocidal Agents/pharmacology , Trypanosoma cruzi/drug effects , Trypanosoma cruzi/physiology , Allopurinol/pharmacology , Allopurinol/therapeutic use , Animals , Cell Line , Cells, Cultured , Chagas Disease/drug therapy , Inhibitory Concentration 50 , Insect Vectors/parasitology , Mice , Mice, Inbred C3H , Muscle Cells/parasitology , Muscles/parasitology , Muscles/pathology , Nicaragua/epidemiology , Nitroimidazoles/pharmacology , Nitroimidazoles/therapeutic use , Phylogeny , Rats , Triatoma/parasitology , Trypanocidal Agents/therapeutic use , Trypanosoma cruzi/classification
SELECTION OF CITATIONS
SEARCH DETAIL
...