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)-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 mediated by proteases, especially as MMPs, have already been described. Methods: We evaluated IL-1β 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-1β 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-1β after stimulation associated with MMP-9 and alternative caspase-1-independent pathway. Conclusions: We suggest some distinct molecular mechanisms for production of IL-1β 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-1β production.
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Authors | Nayara I Medeiros, Bruna F Pinto, Silvana M Elói-Santos, Andréa Teixeira-Carvalho, Luísa M D Magalhães, Walderez O Dutra, Rodrigo Correa-Oliveira, Juliana A S Gomes |
Journal | Frontiers in immunology
(Front Immunol)
Vol. 10
Pg. 800
( 2019)
ISSN: 1664-3224 [Electronic] Switzerland |
PMID | 31057540
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cytokines
- IL1B protein, human
- Inflammasomes
- Interleukin-1beta
- NLR Family, Pyrin Domain-Containing 3 Protein
- Caspase 1
- Matrix Metalloproteinase 2
- Matrix Metalloproteinase 9
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Topics |
- Adult
- Aged
- Caspase 1
(immunology)
- Chagas Cardiomyopathy
(immunology)
- Chagas Disease
(immunology)
- Cytokines
(immunology)
- Female
- Humans
- Immunity, Innate
(immunology)
- Inflammasomes
(immunology)
- Interleukin-1beta
(immunology)
- Male
- Matrix Metalloproteinase 2
(immunology)
- Matrix Metalloproteinase 9
(immunology)
- Middle Aged
- Monocytes
(immunology)
- NLR Family, Pyrin Domain-Containing 3 Protein
(immunology)
- Neutrophils
(immunology)
- Trypanosoma cruzi
(immunology)
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