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.