title: Differential Expression of Matrix Metalloproteinases 2, 9 and Cytokines by Neutrophils and Monocytes in the Clinical Forms of Chagas Disease.
abstract: Dilated cardiomyopathy, the most severe manifestation in chronic phase of Chagas disease, affects about 30% of patients and is characterized by myocardial dysfunction and interstitial fibrosis due to extracellular matrix (ECM) remodeling. ECM remodeling is regulated by proteolytic enzymes such as matrix metalloproteinases (MMPs) and cytokines produced by immune cells, including phagocytes. We evaluated by flow cytometry the expression of MMP-2, MMP-9, IL-1β, TNF-α, TGF-β and IL-10 by neutrophils and monocytes from patients with indeterminate (IND) and cardiac (CARD) clinical forms of Chagas disease and non-infected individuals (NI), before and after in vitro stimulation with Trypanosoma cruzi antigens. Our results showed an important contribution of neutrophils for MMPs production, while monocytes seemed to be involved in cytokine production. The results showed that neutrophils and monocytes from IND and CARD patients had higher intracellular levels of MMP-2 and MMP-9 than NI individuals. On the other hand, T. cruzi derived-antigens promote a differential expression of MMP-2 and MMP-9 in patients with Chagas disease and may regulate MMPs expression in neutrophils and monocytes, mainly when a cardiac alteration is not present. Our data also showed that in the presence of T. cruzi derived-antigens the production of cytokines by neutrophils and monocytes, but mainly by monocytes, may be intensified. Correlation analysis demonstrated that MMP-2 had a positive correlation with IL-10 and a negative correlation with IL-1β, whereas MMP-9 showed a negative correlation with IL-10. We also observed that IND patients presented a greater percentage of high producer cells of regulatory molecules when compared to CARD patients, indicating a different pattern in the immune response. Our data suggest that MMPs and cytokines produced by neutrophils and monocytes are important contributors for cardiac remodeling and may be an interesting target for new biomarker research.
authors.affiliation: Laboratório de Imunologia Celular e Molecular, Centro de Pesquisa René Rachou, FIOCRUZ, Belo Horizonte, Minas Gerais, Brasil.|Laboratório de Biologia das Interações Celulares, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil.
authors.forename: Nayara I
authors.initials: NI
authors.lastname: Medeiros
authors.affiliation: Laboratório de Imunologia Celular e Molecular, Centro de Pesquisa René Rachou, FIOCRUZ, Belo Horizonte, Minas Gerais, Brasil.
authors.forename: Rafaelle C G
authors.initials: RC
authors.lastname: Fares
authors.affiliation: Laboratório de Biologia das Interações Celulares, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil.
authors.forename: Eliza P
authors.initials: EP
authors.lastname: Franco
authors.affiliation: Faculdade de Medicina, Programa de Pós-graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil.
authors.forename: Giovane R
authors.initials: GR
authors.lastname: Sousa
authors.affiliation: Laboratório de Biologia das Interações Celulares, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil.
authors.forename: Rafael T
authors.initials: RT
authors.lastname: Mattos
authors.affiliation: Faculdade de Medicina, Programa de Pós-graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil.
authors.forename: Ana T
authors.initials: AT
authors.lastname: Chaves
authors.affiliation: Faculdade de Medicina, Programa de Pós-graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil.
authors.forename: Maria do Carmo P
authors.initials: MD
authors.lastname: Nunes
authors.affiliation: Laboratório de Biologia das Interações Celulares, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil.|Instituto Nacional de Ciência e Tecnologia em Doenças Topicais (INCT-DT), Belo Horizonte, Minas Gerais, Brasil.
authors.forename: Walderez O
authors.initials: WO
authors.lastname: Dutra
authors.affiliation: Laboratório de Imunologia Celular e Molecular, Centro de Pesquisa René Rachou, FIOCRUZ, Belo Horizonte, Minas Gerais, Brasil.|Instituto Nacional de Ciência e Tecnologia em Doenças Topicais (INCT-DT), Belo Horizonte, Minas Gerais, Brasil.|NUPEB, Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais, Brasil.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Correa-Oliveira
authors.affiliation: Faculdade de Medicina, Programa de Pós-graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil.
authors.forename: Manoel O C
authors.initials: MO
authors.lastname: Rocha
authors.affiliation: Laboratório de Biologia das Interações Celulares, Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil.|Faculdade de Medicina, Programa de Pós-graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil.
authors.forename: Juliana A S
authors.initials: JA
authors.lastname: Gomes
mesh_terms: D000328:Adult; D000368:Aged; D000953:Antigens, Protozoan / Q000276:immunology; D001938:Brazil; D016022:Case-Control Studies; D002598:Chagas Cardiomyopathy / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D016014:Linear Models; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D014349:Trypanosoma cruzi
chemical_list: D000953:Antigens, Protozoan; D016207:Cytokines; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9