Differential Expression of Matrix Metalloproteinases 2, 9 and Cytokines by Neutrophils and Monocytes in the Clinical Forms of Chagas Disease

• Published in: PLoS neglected tropical diseases Vol. 11; no. 1; p. e0005284
• Main Authors: Medeiros, Nayara I, Fares, Rafaelle C G, Franco, Eliza P, Sousa, Giovane R, Mattos, Rafael T, Chaves, Ana T, Nunes, Maria do Carmo P, Dutra, Walderez O, Correa-Oliveira, Rodrigo, Rocha, Manoel O C, Gomes, Juliana A S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.01.2017; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Air fares; Airlines; Antigens; Antigens, Protozoan - immunology; Biology and Life Sciences; Brazil; Cardiomyopathy; Care and treatment; Case-Control Studies; Chagas Cardiomyopathy - immunology; Chagas disease; Cytokines; Cytokines - metabolism; Extracellular matrix; Flow Cytometry; Humans; Inflammation; Laboratories; Linear Models; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; Matrix metalloproteinase inhibitors; Medicine and Health Sciences; Middle Aged; Monocytes; Monocytes - immunology; Neutrophils; Neutrophils - immunology; Tropical diseases; Trypanosoma cruzi; United States > US
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0005284

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.