Immunoregulatory mechanisms in Chagas disease: modulation of apoptosis in T-cell mediated immune responses

Submitted by Nuzia Santos ([email protected]) on 2017-07-17T17:53:45Z No. of bitstreams: 1 Chaves_AnaThereza_Immunoregulatory mechanisms_IRR_2016.pdf: 12736177 bytes, checksum: 7182dae7e3675c77254aa3dd4157a0a9 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2017-07-17T18:03:09Z (GMT) No. of bitstreams: 1 Chaves_AnaThereza_Immunoregulatory mechanisms_IRR_2016.pdf: 12736177 bytes, checksum: 7182dae7e3675c77254aa3dd4157a0a9 (MD5)Made available in DSpace on 2017-07-17T18:03:09Z (GMT). No. of bitstreams: 1 Chaves_AnaThereza_Immunoregulatory mechanisms_IRR_2016.pdf: 12736177 bytes, checksum: 7182dae7e3675c77254aa3dd4157a0a9 (MD5) Previous issue date: 2016Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Laboratório de Biologia das Interações Celulares. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Faculdade de Medicina Programa de Pós graduação em Medicina Tropical e Infectologia. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Laboratório de Biologia das Interações Celulares. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Parasitologia. Laboratório de Imunologia e Genômica de Parasitos. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Parasitologia. Laboratório de Imunologia e Genômica de Parasitos. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Faculdade de Medicina Programa de Pós graduação em Medicina Tropical e Infectologia. Belo Horizonte, MG, Brazil.Laboratório de Imunologia Celular e Molecular, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Brazil/Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Belo Horizonte, MG, Brazil/Universidade Federal de Ouro Preto. Ouro Preto, MG, Brazil.BACKGROUND: Chronic Chagas disease presents different clinical manifestations ranging from asymptomatic (namely indeterminate) to severe cardiac and/or digestive. Previous results have shown that the immune response plays an important role, although no all mechanisms are understood. Immunoregulatory mechanisms such as apoptosis are important for the control of Chagas disease, possibly affecting the morbidity in chronic clinical forms. Apoptosis has been suggested to be an important mechanism of cellular response during T. cruzi infection. We aimed to further understand the putative role of apoptosis in Chagas disease and its relation to the clinical forms of the disease. METHODS: Apoptosis of lymphocytes, under antigenic stimuli (soluble T. cruzi antigens - TcAg) where compared to that of non-stimulated cells. Apoptosis was evaluated using the expression of annexin and caspase 3(+) by T cells and the percentage of cells positive evaluated by flow cytometry. In addition activation and T cell markers were used for the identification of TCD4(+) and TCD8(+) subpopulations. The presence of intracellular and plasma cytokines were also evaluated. Analysis of the activation status of the peripheral blood cells showed that patients with Chagas disease presented higher levels of activation determined by the expression of activation markers, after TcAg stimulation. PCR array were used to evaluate the contribution of this mechanism in specific cell populations from patients with different clinical forms of human Chagas disease. RESULTS: Our results showed a reduced proliferative response associated a high expression of T CD4(+)CD62L(-) cells in CARD patients when compared with IND group and NI individuals. We also observed that both groups of patients presented a significant increase of CD4(+) and CD8(+) T cell subsets in undergoing apoptosis after in vitro stimulation with T. cruzi antigens. In CARD patients, both CD4(+) and CD8(+) T cells expressing TNF-α were highly susceptible to undergo apoptosis after in vitro stimulation. Interestingly, the in vitro TcAg stimulation increased considerably the expression of cell death TNF/TNFR superfamily and Caspase family receptors genes in CARD patients. CONCLUSIONS: Taken together, our results suggest that apoptosis may be an important mechanism for the control of morbidity in T. cruzi infection by modulating the expression of apoptosis genes, the cytokine environment and/or killing of effector cells

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

Evaluation of phenotypic profile of regulatory B cells in different clinical forms of Chagas Disease

Submitted by Repositório Arca ([email protected]) on 2019-05-07T13:26:32Z No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) rafaelle_christine_gomes.pdf: 667519 bytes, checksum: 9ccae729f93074bd0f5f29b04a5cc572 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2019-07-30T18:56:40Z (GMT) No. of bitstreams: 2 rafaelle_christine_gomes.pdf: 667519 bytes, checksum: 9ccae729f93074bd0f5f29b04a5cc572 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Made available in DSpace on 2019-07-30T18:56:40Z (GMT). No. of bitstreams: 2 rafaelle_christine_gomes.pdf: 667519 bytes, checksum: 9ccae729f93074bd0f5f29b04a5cc572 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2010Fundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Belo Horizonte, MG, Brasil.Vários mecanismos imunorreguladores têm sido propostos na infecção causada pelo protozoário T. cruzi como imunossupressão, apoptose e citocinas reguladoras. Recentemente, foi identificada uma nova subpopulação de células B com caracteríticas reguladoras, capazes de suprimir a progressão e/ou melhorar a recuperação de inflamações mediadas pela imunidade adquirida, principalmente pela produção de IL-10 e TGF-. Apesar de existirem relatos sobre alguns marcadores para Bregs em camundongos, não há uma definição clara de uma combinação específica de marcadores para determinar a população das células B reguladoras humana. Atualmente, ainda não existem relatos sobre o papel ou mesmo a presença de células B reguladoras em pacientes portadores da doença de Chagas. Diante disso, nosso objetivo nesse trabalho foi avaliar o perfil fenotípico das células B reguladoras em indivíduos portadores das formas clínicas indeterminada (IND) ou cardíaca (CARD) da doença de Chagas. Nossos resultados mostraram que pacientes apresentando a forma clínica IND possuem maior percentual de células B CD19+CD21+CD1d+, uma das subpopulação de células B reguladoras descrita em modelo murino, no sangue periférico. Adicionalmente, nossos dados mostraram que os pacientes do grupo IND também possuem maior percentual de células B CD19+CD43-CD1d+, outra subpopulação de células B reguladoras, assim como os pacientes do grupo CARD, após estimulação in vitro com antígenos do T. cruzi. Nossos resultados mostraram ainda que as subpopulações de células B CD19+CD21+ e CD19+CD43- dos pacientes com a forma clínica CARD apresentaram maior expressão intracitoplasmática de IL-10. Por outro lado, a expressão intracitoplasmática de TGF- foi maior nos linfócitos B reguladores dos indivíduos do grupo NI. Além disso, as células B CD19+ dos pacientes portadores da doença de Chagas apresentam maior expressão de marcadores de ativação e de apoptose. De fato, ainda são necessários estudos adicionais para melhor compreender a atividade funcional das células B reguladoras durante a infecção por T cruzi. No entanto, nossos dados reforçam a importância dos mecanismos de imunorregulação no desenvolvimento da doença de Chagas, sugerindo que a resposta imune contra o T. cruzi pode ser regulada por vários mecanismos supressores do hospedeiro e que os mecanismos reguladores desenvolvidos pelos indivíduos portadores das diferentes formas clínicas são distintos

Estudo da metaloproteinases 2 e 9 e seus inibidores nas formas clínicas indeterminada e cardíaca da doença de Chagas

Submitted by Nuzia Santos ([email protected]) on 2013-08-07T14:09:58Z No. of bitstreams: 1 Tese_RafaelleCGomesFaresGusmão.pdf: 2582678 bytes, checksum: c69c8890c0878586f273089f5214d41f (MD5)Made available in DSpace on 2013-08-07T14:09:58Z (GMT). No. of bitstreams: 1 Tese_RafaelleCGomesFaresGusmão.pdf: 2582678 bytes, checksum: c69c8890c0878586f273089f5214d41f (MD5) Previous issue date: 2013Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil.A cardiomiopatia dilatada crônica decorrente da infecção pelo T. cruzi está associada com o remodelamento do miocárdio e com a fibrose intersticial, o que resulta em mudanças significativas da matriz extracelular (MEC). O remodelamento da MEC é regulado por enzimas proteolíticas como as metaloproteinases de matriz (MMPs). Nesse estudo, avaliamos pela primeira vez o envolvimento das MMPs 2 e 9 e seus inibidores (TIMPs) em pacientes portadores das formas clínicas indeterminada (IND) e cardíaca (CARD) da doença de Chagas. Nossos resultados mostraram que os níveis séricos da MMP-9 estão associados com a gravidade do acometimento cardíaco e que a MMP-9 possui maior potencial de atividade proteolítica no soro de pacientes CARD. Os níveis séricos de TIMP-1 não apresentaram diferenças estatísticas entre os grupos estudados. Por outro lado, os níveis séricos de TIMP-2 foram maiores no grupo CARD. A partir da análise de correlação, foi possível observar uma possível especificidade do TIMP-1 pela MMP-9. A análise da produção de MMPs por linfócitos T e monócitos mostrou que essas células do sistema imune são capazes de produzir MMP-2 e MMP-9 e, ainda que linfócitos T CD8+ são as principais células mononucleares produtoras de MMP-2 e MMP-9. A partir da cultura tridimensional de cardiomiócitos de camundongos, observamos que existem componentes no soro dos pacientes com doença de Chagas capazes de induzir a expressão de componentes da matriz extracelular no microtecido cardíaco. Além disso, MMP-2 apresentou correlação negativa com proteínas de matriz (laminina e fibronectina) e com citocinas inflamatórias (TNF-IL-6 e IL-1), enquanto que a MMP-9 apresentou correlação positiva com proteínas de matriz (laminina e fibronectina) e com a citocina inflamatória IL-1. A partir da análise da ocorrência de polimorfismos de nucleotídeo único, não foi possível observar influência da genética do hospedeiro sobre os níveis séricos das MMPs 2 e 9 e seus inibidores, bem como sobre a morbidade da doença de Chagas. Nossos resultados sugerem que MMP-2 e MMP-9 participam de maneira diferente na patogênese da doença de Chagas, sendo que a MMP-9 parece estar mais envolvida no processo inflamatório e no remodelamento cardíaco. Em resumo, nossos resultados mostram, pela primeira vez, o envolvimento da MMP-9, mas não da MMP-2, na cardiomiopatia chagásica. Esses dados são inovadores e representam um avanço no conhecimento dos mecanismos envolvidos no estabelecimento e manutenção da patologia do acometimento cardíaco na doença de Chagas.Dilated chronic cardiomyopathy (DCC) in Chagas disease is associated with myocardial remodeling and interstitial fibrosis, resulting in significant extracellular matrix (ECM) modifications. ECM remodeling is regulatedby proteolytic enzymes such as matrix metalloproteinases (MMPs). In this study, we evaluated, for the first time, the serum MMPs 2 and 9 levels, as well as their main cell sources in the peripheral blood from patients presenting the indeterminate (IND) or cardiac (CARD) clinical forms of Chagas disease. Our results showed that MMP-9 serum levels are associated with the severity of Chagas disease. The serum levels of TIMP-1 were not different between the studied groups; however the serum levels of TIMP-2 were higher in CARD group.The correlation analysis showed a possible specificity of TIMP-1 for MMP-9. The analysis of MMPs production by T lymphocytes showed that CD8+ T cells are the main source of both MMP-2 and MMP-9 molecules. Using a new 3-dimensional model of fibrosis we also observed that serum from patients with Chagas disease induced an increase in the extracellular matrix components in cardiac spheroids obtained from mice cardiomyocytes. Furthermore, MMP-2 and MMP-9 have showed different profile of correlation with matrixproteins (laminin and fibronectin) and inflammatory cytokines (TNF-and IL-1) in patients with Chagas disease. Our results suggest that MMP-2 and MMP-9 show distinct activities in Chagas disease pathogenesis. While MMP-9 seems to be involved with the inflammation and cardiac remodeling of Chagas disease, MMP-2 does not show any correlation with inflammatory molecules. There are many factors involved in the determination of the severity and progression of Chagas disease, and host genetics is certainly a contributing factor for the development of the disease. Therefore, we evaluated whether there were significant polymorphisms in MMPs and TIMPs genes. Our results did not show any association between polymorphisms occurrence and morbidity of the disease. In conclusion, our datastress the involvement of MMP-9, and not of MMP-2, in heart disease and, for the first time, its participation in chagasic cardiomyopathy. These data are innovative and represent an advance in the knowledge of the mechanisms involved in the establishment/maintenance of the Chagas heart disease pathology

Chronic Low-Grade Inflammation in Childhood Obesity Is Associated with Decreased IL-10 Expression by Monocyte Subsets

Submitted by Nuzia Santos ([email protected]) on 2017-12-13T16:42:49Z No. of bitstreams: 1 Chronic Low-Grade Inflammation in Childhood Obesity.pdf: 7367809 bytes, checksum: 7fe44c78117bdbeba3fb468364e5ffbb (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2017-12-13T16:49:29Z (GMT) No. of bitstreams: 1 Chronic Low-Grade Inflammation in Childhood Obesity.pdf: 7367809 bytes, checksum: 7fe44c78117bdbeba3fb468364e5ffbb (MD5)Made available in DSpace on 2017-12-13T16:49:29Z (GMT). No. of bitstreams: 1 Chronic Low-Grade Inflammation in Childhood Obesity.pdf: 7367809 bytes, checksum: 7fe44c78117bdbeba3fb468364e5ffbb (MD5) Previous issue date: 2016FAPEMIG/CNPqUniversidade Federal de Minas Gerais. Instituto de Ciências Biologicas. Departamento de Morfologia. Laboratorio de Biologia das Interacões Celulares. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Instituto de Ciências Biologicas. Departamento de Morfologia. Laboratorio de Biologia das Interacões Celulares. Belo Horizonte, MG, Brasil/Fundação Oswaldo Cruz. Instituto Rene Rachou. Laboratorio de Imunologia Celular e Molecular. Belo Horizonte, MG, BrasilUniversidade Estadual de Santa Cruz. Departamento de Genetica. Ilheus, BA, Brasil/Servico de Medicina Preventiva da Unimed. Aracaju, SE, BrasilFundação Oswaldo Cruz. Instituto Rene Rachou. Laboratorio de Imunologia Celular e Molecular. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Instituto de Ciências Biologicas. Departamento de Morfologia. Laboratorio de Biologia das Interacões Celulares. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Instituto de Ciências Biologicas. Departamento de Morfologia. Laboratorio de Biologia das Interacões Celulares. Belo Horizonte, MG, Brasil/ Instituto Nacional de Ciência e Tecnologia em Doencas Tropicais—INCT-DTUniversidade Federal de Mato Grasso. Departamento de Ciências Basicas da Saude. Faculdade de Medicina. Cuiaba, MT, BrasilFundação Oswaldo Cruz. Instituto Rene Rachou. Laboratorio de Imunologia Celular e Molecular. Belo Horizonte, MG, Brasil/ Instituto Nacional de Ciência e Tecnologia em Doencas Tropicais—INCT-DTUniversidade Federal de Minas Gerais. Instituto de Ciências Biologicas. Departamento de Morfologia. Laboratorio de Biologia das Interacões Celulares. Belo Horizonte, MG, BrasilChronic low-grade inflammation is related to the development of comorbidities and poor prognosis in obesity. Monocytes are main sources of cytokines and play a pivotal role in inflammation. We evaluated monocyte frequency, phenotype and cytokine profile of monocyte subsets, to determine their association with the pathogenesis of childhood obesity. Children with obesity were evaluated for biochemical and anthropometric parameters. Monocyte subsets were characterized by flow cytometry, considering cytokine production and activation/recognition molecules. Correlation analysis between clinical parameters and immunological data delineated the monocytes contribution for low-grade inflammation. We observed a higher frequency of non-classical monocytes in the childhood obesity group (CO) than normal-weight group (NW). All subsets displayed higher TLR4 expression in CO, but their recognition and antigen presentation functions seem to be diminished due to lower expression of CD40, CD80/86 and HLA-DR. All subsets showed a lower expression of IL-10 in CO and correlation analyses showed changes in IL-10 expression profile. The lower expression of IL-10 may be decisive for the maintenance of the low-grade inflammation status in CO, especially for alterations in non-classical monocytes profile. These cells may contribute to supporting inflammation and loss of regulation in the immune response of children with obesity

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

Plasma Cytokine Expression Is Associated with Cardiac Morbidity in Chagas Disease

Submitted by Nuzia Santos ([email protected]) on 2015-02-06T13:25:14Z No. of bitstreams: 1 2014_048.pdf: 2077033 bytes, checksum: 5c9786393949bf065beeeb0aad05f1bd (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-02-06T13:25:21Z (GMT) No. of bitstreams: 1 2014_048.pdf: 2077033 bytes, checksum: 5c9786393949bf065beeeb0aad05f1bd (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-02-06T14:27:57Z (GMT) No. of bitstreams: 1 2014_048.pdf: 2077033 bytes, checksum: 5c9786393949bf065beeeb0aad05f1bd (MD5)Made available in DSpace on 2015-02-06T14:27:57Z (GMT). No. of bitstreams: 1 2014_048.pdf: 2077033 bytes, checksum: 5c9786393949bf065beeeb0aad05f1bd (MD5) Previous issue date: 2014Universidade Federal de Minas Gerais. Faculdade de Medicina. Infectologia e Medicina Tropical. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Faculdade de Medicina. Infectologia e Medicina Tropical. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Morfologia. Belo Horizonte, Minas Gerais, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratorio de Imunologia Celular e Molecular. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Morfologia. Belo Horizonte, Minas Gerais, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratorio de Imunologia Celular e Molecular. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Morfologia. Belo Horizonte, Minas Gerais, BrazilUniversidade Federal de Minas Gerais. Faculdade de Medicina. Infectologia e Medicina Tropical. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratorio de Imunologia Celular e Molecular. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciencias Biologicas. Departamento de Morfologia. Belo Horizonte, Minas Gerais, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Laboratorio de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil/Instituto Nacional de Ciencia e Tecnologia em Doenças Tropicais. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Faculdade de Medicina. Infectologia e Medicina Tropical. Belo Horizonte, MG, BrazilThe expression of immune response appears to be associated with morbidity in Chagas disease. However, the studies in this field have usually employed small samples of patients and statistical analyses that do not consider the wide dispersion of cytokine production observed in these patients. The aim of this study was to evaluate the plasma cytokine levels in welldefined clinical polar groups of chagasic patients divided into categories that better reflect the wide cytokine profile and its relationship with morbidity. Patients infected with Trypanosoma cruzi (T. cruzi) were grouped as indeterminate (IND) and cardiac (CARD) forms ranging from 23 to 69 years of age (mean of 45.6611.25). The IND group included 82 individuals, ranging from 24 to 66 years of age (mean of 39.6610.3). The CARD group included 94 patients ranging from 23 to 69 years of age (mean of 48612.52) presenting dilated cardiomyopathy. None of the patients have undergone chemotherapeutic treatment, nor had been previously treated for T. cruzi infection. Healthy non-chagasic individuals, ranging from 29 to 55 years of age (mean of 42.668.8) were included as a control group (NI). IND patients have a higher intensity of interleukin 10 (IL-10) expression when compared with individuals in the other groups. By contrast, inflammatory cytokine expression, such as interferon gamma (IFN-c), tumor necrosis factor alpha (TNF-a), interleukin 6 (IL-6), and interleukin 1 beta (IL-1b), proved to be the highest in the CARD group. Correlation analysis showed that higher IL-10 expression was associated with better cardiac function, as determined by left ventricular ejection fraction and left ventricular diastolic diameter values. Altogether, these findings reinforce the concept that a fine balance between regulatory and inflammatory cytokines represents a key element in the establishment of distinct forms of chronic Chagas disease

Matrix Metalloproteinases 2 and 9 Are Differentially Expressed in Patients with Indeterminate and Cardiac Clinical Forms of Chagas Disease

Made available in DSpace on 2015-09-28T13:02:37Z (GMT). No. of bitstreams: 2 license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) luciana_garzoni_etal_IOC_2013.pdf: 1928957 bytes, checksum: 7cfd5f51da07c835cf156cca694e6005 (MD5) Previous issue date: 2013Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultra-Estrutura Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultra-Estrutura Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Evandro Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Faculdade de Medicina. Programa de Pós-Graduação em Ciências da Saúde, Infectologia e Medicina Tropical. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Faculdade de Medicina. Programa de Pós-Graduação em Ciências da Saúde, Infectologia e Medicina Tropical. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, Brasil / Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais INCT-DT. Belo Horizonte, MG, Brasil.Dilated chronic cardiomyopathy (DCC) from Chagas disease is associated with myocardial remodeling and interstitial fibrosis, resulting in extracellular matrix (ECM) changes. In this study, we characterized for the first time the serum matrix metalloproteinase 2 (MMP-2) and MMP-9 levels, as well as their main cell sources in peripheral blood mononuclear cells from patients presenting with the indeterminate (IND) or cardiac (CARD) clinical form of Chagas disease. Our results showed that serum levels of MMP-9 are associated with the severity of Chagas disease. The analysis of MMP production by T lymphocytes showed that CD8 T cells are the main mononuclear leukocyte source of both MMP-2 and MMP-9 molecules. Using a new 3-dimensional model of fibrosis, we observed that sera from patients with Chagas disease induced an increase in the extracellular matrix components in cardiac spheroids. Furthermore, MMP-2 and MMP-9 showed different correlations with matrix proteins and inflammatory cytokines in patients with Chagas disease. Our results suggest that MMP-2 and MMP-9 show distinct activities in Chagas disease pathogenesis. While MMP-9 seems to be involved in the inflammation and cardiac remodeling of Chagas disease, MMP-2 does not correlate with inflammatory molecules