Evidence of Different IL-1β Activation Pathways in Innate Immune Cells From Indeterminate and Cardiac Patients With Chronic Chagas Disease
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 convert...
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Frontiers Media S.A.
2019-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00800/full |
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| author | Nayara I. Medeiros Nayara I. Medeiros Bruna F. Pinto Silvana M. Elói-Santos Silvana M. Elói-Santos Andréa Teixeira-Carvalho Luísa M. D. Magalhães Walderez O. Dutra Walderez O. Dutra Rodrigo Correa-Oliveira Rodrigo Correa-Oliveira Juliana A. S. Gomes |
| author_facet | Nayara I. Medeiros Nayara I. Medeiros Bruna F. Pinto Silvana M. Elói-Santos Silvana M. Elói-Santos Andréa Teixeira-Carvalho Luísa M. D. Magalhães Walderez O. Dutra Walderez O. Dutra Rodrigo Correa-Oliveira Rodrigo Correa-Oliveira Juliana A. S. Gomes |
| author_sort | Nayara I. Medeiros |
| collection | DOAJ |
| description | 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 disease1 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. |
| first_indexed | 2024-12-23T11:44:54Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T11:44:54Z |
| publishDate | 2019-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-16fba40d2891460b9969103cbccb4ccc2022-12-21T17:48:22ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-04-011010.3389/fimmu.2019.00800439030Evidence of Different IL-1β Activation Pathways in Innate Immune Cells From Indeterminate and Cardiac Patients With Chronic Chagas DiseaseNayara I. Medeiros0Nayara I. Medeiros1Bruna F. Pinto2Silvana M. Elói-Santos3Silvana M. Elói-Santos4Andréa Teixeira-Carvalho5Luísa M. D. Magalhães6Walderez O. Dutra7Walderez O. Dutra8Rodrigo Correa-Oliveira9Rodrigo Correa-Oliveira10Juliana A. S. Gomes11Imunologia Celular e Molecular, Instituto René Rachou, FIOCRUZ, Belo Horizonte, BrazilLaboratório de Biologia das Interações Celulares, Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilLaboratório de Biologia das Interações Celulares, Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilGrupo Integrado de Pesquisas em Biomarcadores, Instituto René Rachou, FIOCRUZ, Belo Horizonte, BrazilDepartamento de Propedêutica Complementar, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilGrupo Integrado de Pesquisas em Biomarcadores, Instituto René Rachou, FIOCRUZ, Belo Horizonte, BrazilInflammatory Cell Dynamics Section, Center for Cancer Research, National Institute of Health, NIH, Bethesda, MD, United StatesLaboratório de Biologia das Interações Celulares, Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilInstituto Nacional de Ciência e Tecnologia em Doenças Topicais - INCT-DT, Belo Horizonte, BrazilImunologia Celular e Molecular, Instituto René Rachou, FIOCRUZ, Belo Horizonte, BrazilInstituto Nacional de Ciência e Tecnologia em Doenças Topicais - INCT-DT, Belo Horizonte, BrazilLaboratório de Biologia das Interações Celulares, Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilBackground: 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 disease1 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.00800/fullIL-1β activation pathwayscaspase-1-independentgelatinasesChagas diseasechagasic cardiomyopathy |
| spellingShingle | Nayara I. Medeiros Nayara I. Medeiros Bruna F. Pinto Silvana M. Elói-Santos Silvana M. Elói-Santos Andréa Teixeira-Carvalho Luísa M. D. Magalhães Walderez O. Dutra Walderez O. Dutra Rodrigo Correa-Oliveira Rodrigo Correa-Oliveira Juliana A. S. Gomes Evidence of Different IL-1β Activation Pathways in Innate Immune Cells From Indeterminate and Cardiac Patients With Chronic Chagas Disease Frontiers in Immunology IL-1β activation pathways caspase-1-independent gelatinases Chagas disease chagasic cardiomyopathy |
| title | Evidence of Different IL-1β Activation Pathways in Innate Immune Cells From Indeterminate and Cardiac Patients With Chronic Chagas Disease |
| title_full | Evidence of Different IL-1β Activation Pathways in Innate Immune Cells From Indeterminate and Cardiac Patients With Chronic Chagas Disease |
| title_fullStr | Evidence of Different IL-1β Activation Pathways in Innate Immune Cells From Indeterminate and Cardiac Patients With Chronic Chagas Disease |
| title_full_unstemmed | Evidence of Different IL-1β Activation Pathways in Innate Immune Cells From Indeterminate and Cardiac Patients With Chronic Chagas Disease |
| title_short | Evidence of Different IL-1β Activation Pathways in Innate Immune Cells From Indeterminate and Cardiac Patients With Chronic Chagas Disease |
| title_sort | evidence of different il 1β activation pathways in innate immune cells from indeterminate and cardiac patients with chronic chagas disease |
| topic | IL-1β activation pathways caspase-1-independent gelatinases Chagas disease chagasic cardiomyopathy |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.00800/full |
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