Profile of Central and Effector Memory T Cells in the Progression of Chronic Human Chagas Disease

Chagas disease is a parasitic infection caused by protozoan Trypanosoma cruzi that affects approximately 11 million people in Latin America. The involvement of the host's immune response on the development of severe forms of Chagas disease has not been fully elucidated. Studies on the immune response against T. cruzi infection show that the immunoregulatory mechanisms are necessary to prevent the deleterious effect of excessive immune response stimulation and consequently the fatal outcome of the disease. A recall response against parasite antigens observed in in vitro peripheral blood cell culture clearly demonstrates that memory response is generated during infection. Memory T cells are heterogeneous and differ in both the ability to migrate and exert their effector function. This heterogeneity is reflected in the definition of central (TCM) and effector memory (TEM) T cells. Our results suggest that a balance between regulatory and effectors T cells may be important for the progression and development of the disease. Furthermore, the high percentage of central memory CD4+ T cells in indeterminate patients after stimulation suggests that these cells may modulate host's inflammatory response by controlling cell migration to tissues and their effector role during chronic phase of the disease

Cytokine profile, proliferation and phosphorylation of ERK1/2 and Akt in circulating mononuclear cells from individuals during the chronic intestinal phase of <it>Schistosomiasis mansoni</it> infection

Abstract Background The immune response to Schistosoma mansoni is characterized by a granulomatous reaction around the parasite eggs that are trapped in the host liver, and this reaction modulates the immune response during the chronic phase of the disease. The typical peripheral blood mononuclear cell (PBMC) response of patients during the chronic intestinal phase of infection is characterized by a decreased response to an S. mansoni soluble egg antigen. To obtain a greater understanding of Schistosoma infections, this study investigated the effects of the soluble egg antigen (SEA) and soluble adult worm antigen (SWAP) of S. mansoni on cellular proliferation, cytokine production, and ERK1/2 and Akt phosphorylation in PBMCs from infected (XTO) and egg-negative (NI) individuals living in the same endemic area. Methods The activation status was evaluated by cell immunophenotypic staining (cytometry). The cell proliferation assay was by CFSE method. Cytokine detection assay (Th1 and Th2) was by Cytometric Bead and Array phosphorylation status was by ELISA. Results The XTO, NI and BD (blood donor) individuals from an area not endemic for schistosomiasis were compared. The CD4+ T lymphocyte proliferation rate was lower in the XTO group, but not the NI group, after SEA stimulation compared to the BD group. The CD8+ T cell proliferation rate was lower in the XTO group in the unstimulated cultures and after both SEA and SWAP stimulation compared to the BD group. Cytokine analysis after either SEA or SWAP stimulation showed a balanced cytokine pattern in the XTO and NI groups. ERK1/2 and Akt phosphorylation were only marginally detected in all groups; however, a decrease in ERK 1/2 phosphorylation was observed in the SWAP-stimulated XTO group compared to both the NI and BD groups. Conclusions The data indicate that SEA-stimulated CD4+ T cells from infected patients have a lower proliferation rate than the same cells from the NI group. Furthermore, we observed that SWAP stimulation influences ERK1/2 phosphorylation in the XTO group.</p

Cytokine profile, proliferation and phosphorylation of ERK1/2 and Akt in circulating mononuclear cells from individuals during the chronic intestinal phase of Schistosomiasis mansoni infection

Submitted by Nuzia Santos ([email protected]) on 2014-06-16T12:44:46Z No. of bitstreams: 1 Cytokine profile.pdf: 3149759 bytes, checksum: cf43916157d8279f1d5361396fd1143b (MD5)Made available in DSpace on 2014-06-16T12:44:46Z (GMT). No. of bitstreams: 1 Cytokine profile.pdf: 3149759 bytes, checksum: cf43916157d8279f1d5361396fd1143b (MD5) Previous issue date: 2012Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Escola de Enfermagem. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais.Escola de Enfermagem. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Brasilia, DF, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Faculdade de Medicina. Departamento de Clínica Médica, Cirurgia. Belo Horizonte, MG, Brazil/Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Belo Horizonte, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brazil/Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Belo Horizonte, BrazilUniversidade Federal de Minas Gerais. Faculdade de Medicina. Departamento de Cirurgia. Belo Horizonte, MG, BrazilBackground :The immune response to Schistosoma mansoni is characterized by a granulomatous reaction around the parasite eggs that are trapped in the host liver, and this reaction modulates the immune response during the chronic phase of the disease. The typical peripheral blood mononuclear cell (PBMC) response of patients during the chronic intestinal phase of infection is characterized by a decreased response to an S. mansoni soluble egg antigen. To obtain a greater understanding of Schistosoma infections, this study investigated the effects of the soluble egg antigen (SEA) and soluble adult worm antigen (SWAP) of S. mansoni on cellular proliferation, cytokine production, and ERK1/2 and Akt phosphorylation in PBMCs from infected (XTO) and egg-negative (NI) individuals living in the same endemic area. Methods : The activation status was evaluated by cell immunophenotypic staining (cytometry). The cell proliferation assay was by CFSE method. Cytokine detection assay (Th1 and Th2) was by Cytometric Bead and Array phosphorylation status was by ELISA. Results : The XTO, NI and BD (blood donor) individuals from an area not endemic for schistosomiasis were compared. The CD4+ T lymphocyte proliferation rate was lower in the XTO group, but not the NI group, after SEA stimulation compared to the BD group. The CD8+ T cell proliferation rate was lower in the XTO group in the unstimulated cultures and after both SEA and SWAP stimulation compared to the BD group. Cytokine analysis after either SEA or SWAP stimulation showed a balanced cytokine pattern in the XTO and NI groups. ERK1/2 and Akt phosphorylation were only marginally detected in all groups; however, a decrease in ERK 1/2 phosphorylation was observed in the SWAP-stimulated XTO group compared to both the NI and BD groups. Conclusions : The data indicate that SEA-stimulated CD4+ T cells from infected patients have a lower proliferation rate than the same cells from the NI group. Furthermore, we observed that SWAP stimulation influences ERK1/2 phosphorylation in the XTO group

Correlation analysis between plasma IL-10 levels and echocardiographic variable markers of cardiac morbidity.

<p>Correlation analysis between plasma IL-10 levels and cardiac function variables (LVEF and LVDD) in the IND (n = 82, first column) and CARD (n = 94, second column) groups. Correlation analysis was performed using the Spearman correlation coefficient, and results were considered significant when <i>P</i><0.05. Significant differences (<i>P</i>-value) are indicated in each graph together with the <i>r</i> value.</p

Analyses of plasma cytokine levels and their association with cardiac morbidity expressed by the clinical classification.

<p>The analysis of plasma levels was performed as described in the material and methods section. The groups evaluated were: NI (n = 24, white box), IND (n = 82, light gray box), and CARD (n = 94, dark gray box). The results were expressed by mean intensity of fluorescence (MIF). (A) Plasma IL-10 levels in NI, IND, and CARD groups and their association with cardiac morbidity. (B) Plasma IFN-γ levels in NI, IND, and CARD groups and their association with cardiac morbidity. (C) Plasma TNF-α levels in NI, IND, and CARD groups and their association with cardiac morbidity. (D) Plasma IL-6 levels in NI, IND, and CARD groups and their association with cardiac morbidity. E) Plasma IL-1β levels in NI, IND, and CARD groups and their association with cardiac morbidity. Significant differences (<i>P</i>-value<0.05) in the charts are identified by connecting lines and the symbol (*) for comparisons between the groups.</p