6 research outputs found
Immunoregulatory mechanisms in Chagas disease: modulation of apoptosis in T-cell mediated immune responses
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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 BiofÃsica. 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
CXCL-16, IL-17, and bone morphogenetic protein 2 (BMP-2) are associated with overweight and obesity conditions in middle-aged and elderly women.
The current concept of overweight/obesity is most likely related to a combination of increased caloric
intake and decreased energy expenditure. Widespread inflammation, associated with both conditions, appears to
contribute to the development of some obesity-related comorbidities. Interventions that directly or indirectly target
individuals at high risk of developing obesity have been largely proposed because of the increasing number of
overweight/obese cases worldwide. The aim of the present study was to assess CXCL16, IL-17, and BMP-2 plasma
factors in middle-aged and elderly women and relate them to an overweight or obese status. In total, 117 women
were selected and grouped as eutrophic, overweight, and obese, according to anthropometric parameters. Analyses
of anthropometric and circulating biochemical parameters were followed by plasma immunoassays for CXCL-16, IL-
17, and BMP-2
Interleukin-10 rs2227307 and CXCR2 rs1126579 polymorphisms modulate the predisposition to septic shock
Despite major improvements in its treatment and diagnosis, sepsis is still a leading cause of death and admittance to the intensive care unit (ICU). Failure to identify patients at high risk of developing septic shock contributes to an increase in the sepsis burden and rapid molecular tests are currently the most promising avenue to aid in patient risk determination and therapeutic anticipation. The primary goal of this study was to evaluate the genetic susceptibility that affects sepsis outcome in 72 sepsis patients admitted to the ICU. Seven polymorphisms were genotyped in key inflammatory response genes in sepsis, including tumour necrosis factor-α, interlelukin (IL)-1β, IL-10, IL-8, Toll-like receptor 4, CXCR1 and CXCR2. The primary finding showed that patients who were homozygous for the major A allele in IL-10 rs1800896 had almost five times higher chance to develop septic shock compared to heterozygotes. Similarly, selected clinical features and CXCR2 rs1126579 single nucleotide polymorphisms modulated septic shock susceptibility without affecting survival. These data support the hypothesis that molecular testing has clinical usefulness to improve sepsis prognostic models. Therefore, enrichment of the ICU portfolio by including these biomarkers will aid in the early identification of sepsis patients who may develop septic shock
The overweight increases circulating inflammatory mediators commonly associated with obesity in young individuals.
Obesity is a serious and growing world healthy problem affecting developed and developing countries. The new conception of obesity as a basal inflammatory condition has opened a new window of possibilities to identify inflammatory biomarkers to be used in the diagnosis or prognosis of obesity-associated comorbidities. This present work aims the identification of the adipokines (leptin and resistin), chemokines (CCL2, CCL5, CXCL16) and the BMP-2 and their association with the clinical, biochemical (fasting glucose, hemogram, cholesterol, T3, T4 and TSH) and anthropometric (weight, height, body circumferences, skinfold thickness and percentage of body fat) parameters in young adults (18?30?years old) presenting obesity and overweight. Our data showed increasing in anthropometric parameters and in the plasma inflammatory levels in those individuals presenting overweight and obesity. We observed a higher plasma levels of CCL2, CCL5, CXCL16, leptin and resistin in those overweigh and obese individuals. In addition, the CCL2, CCL5 presented a positive correlation with the body mass index and the body fat percentage. Assuming the obesity as a systemic inflammatory process, in this current study, the overweight individuals possess a close similar pattern of circulating inflammatory mediators which might be a potential risk of the development of obesity comorbidities. Further studies are still needed to precise the role of the biomarkers CCL2, CCL5, CXCL16 and BMP-2 in the clinical prognosis related to the overweight or obese individuals
Additional file 1: Figure S1. of Immunoregulatory mechanisms in Chagas disease: modulation of apoptosis in T-cell mediated immune responses
Analyses of plasma cytokine levels expressed by the clinical classification. The analysis of plasma levels was performed as described in material and methods. The groups evaluated were: NI (n = 15, white box), IND (n = 15, light gray box), and CARD (n = 15, dark gray box). The results were expressed by mean intensity of fluorescence (MIF). (A) Plasma TNF-α levels in NI, IND, and CARD groups. (B) Plasma IL-2 levels in NI, IND, and CARD groups. (C) Plasma IFN-γ levels in NI, IND, and CARD groups. (D) Plasma IL-10 levels in NI, IND, and CARD groups. Significant differences (P-value < 0.05). Statistical comparative analyses were performed, in groups of two, between the NI, IND, and CARD groups, using the non-parametric Kruskal-Wallis test and Mann–Whitney U test, together with the Bonferroni correction (significance level, 0.05/3 = 0.0167). The letters represent statistically significant differences (p < 0.05) between the groups: a = difference when compared to NI group; b = difference when compared to IND group; c = difference when compared to CARD group. (PDF 113 kb