Dataset Information

Evidence of Different IL-1? Activation Pathways in Innate Immune Cells From Indeterminate and Cardiac Patients With Chronic Chagas Disease.

ABSTRACT: Background: Chagas cardiomyopathy is the main fibrosing myocarditis among known heart diseases. Development of cardiomyopathy has been related to extracellular matrix (ECM) remodeling, which are controlled by matrix metalloproteinases (MMPs) and cytokines, especially interleukin (IL)-1?. The convertion of 31KDa inactive precursor, the proIL-1? in 17KDa active IL-1? peptide, is controlled by caspase-1-dependent pathway, associated with inflammasomes. Other caspase-1 independent mechanisms mediated by proteases, especially as MMPs, have already been described. Methods: We evaluated IL-1? activation pathways in neutrophils and monocyte subsets from patients with different clinical forms of Chagas disease after T. cruzi antigen stimulation by multiparameter flow cytometry. Results: Our data demonstrated that Chagas patients with the indeterminate clinical form (IND) showed increased levels of IL-1? post-stimulation as well as increased expression of MMP-2, NLRP3, and CASP1, which are associated with the classical caspase-1-dependent pathway. Conversely, patients with the cardiac clinical form (CARD) showed increased IL-1? after stimulation associated with MMP-9 and alternative caspase-1-independent pathway. Conclusions: We suggest some distinct molecular mechanisms for production of IL-1? in innate immune cells from patients with different clinical forms of Chagas disease. MMP-2 and MMP-9 gelatinases are associated with distinct disease outcomes and IL-1? production.

SUBMITTER: Medeiros NI

PROVIDER: S-EPMC6482163 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Evidence of Different IL-1β Activation Pathways in Innate Immune Cells From Indeterminate and Cardiac Patients With Chronic Chagas Disease.

Medeiros Nayara I NI Pinto Bruna F BF Elói-Santos Silvana M SM Teixeira-Carvalho Andréa A Magalhães Luísa M D LMD Dutra Walderez O WO Correa-Oliveira Rodrigo R Gomes Juliana A S JAS

Frontiers in immunology 20190418

<b>Background:</b> Chagas cardiomyopathy is the main fibrosing myocarditis among known heart diseases. Development of cardiomyopathy has been related to extracellular matrix (ECM) remodeling, which are controlled by matrix metalloproteinases (MMPs) and cytokines, especially interleukin (IL)-1β. The convertion of 31KDa inactive precursor, the proIL-1β in 17KDa active IL-1β peptide, is controlled by caspase-1-dependent pathway, associated with inflammasomes. Other caspase-1 independent mechanisms ...[more]

PMID: 31057540

Similar Datasets

Project description:Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a neglected tropical disease and a health problem in Latin America. Etiological treatment has limited effectiveness in chronic CD; thus, new therapeutic strategies are required. The practice of physical exercises has been widely advocated to improve the quality of life of CD patients. The most frequent clinical CD manifestation is the chronic indeterminate form (CIF), and the effect of physical exercises on disease progression remains unknown. Here, in a CIF model, we aimed to evaluate the effect of physical exercises on cardiac histological, parasitological, mitochondrial, and oxidative metabolism, electro and echocardiographic profiles, and immunological features. To establish a CIF model, BALB/c and C57BL/6 mice were infected with 100 and 500 trypomastigotes of the Y T. cruzi strain. At 120 days postinfection (dpi), all mouse groups showed normal PR and corrected QT intervals and QRS complexes. Compared to BALB/c mice, C57BL/6 mice showed a lower parasitemia peak, mortality rate, and less intense myocarditis. Thus, C57BL/6 mice infected with 500 parasites were used for subsequent analyses. At 120 dpi, a decrease in cardiac mitochondrial oxygen consumption and an increase in reactive oxygen species (ROS) were detected. When we increased the number of analyzed mice, a reduced heart rate and slightly prolonged corrected QT intervals were detected, at 120 and 150 dpi, which were then normalized at 180 dpi, thus characterizing the CIF. Y-infected mice were subjected to an exercise program on a treadmill for 4 weeks (from 150 to 180 dpi), five times per week in a 30-60-min daily training session. At 180 dpi, no alterations were detected in cardiac mitochondrial and oxidative metabolism, which were not affected by physical exercises, although ROS production increased. At 120 and 180 dpi, comparing infected and non-infected mice, no differences were observed in the levels of plasma cytokines, indicating that a crucial biomarker of the systemic inflammatory profile was absent and not affected by exercise. Compared with sedentary mice, trained Y-infected mice showed similar parasite loads and inflammatory cells but reduced cardiac fibrosis. Therefore, our data show that physical exercises promote beneficial changes that may prevent CD progression.

Dataset Information

Evidence of Different IL-1? Activation Pathways in Innate Immune Cells From Indeterminate and Cardiac Patients With Chronic Chagas Disease.

Publications

Evidence of Different IL-1β Activation Pathways in Innate Immune Cells From Indeterminate and Cardiac Patients With Chronic Chagas Disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets