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

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-1ß, TNF-α, TGF-ß 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-1ß, 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.

Chronic Low-Grade Inflammation in Childhood Obesity Is Associated with Decreased IL-10 Expression by Monocyte Subsets.

Chronic low-grade inflammation is related to the development of comorbidities and poor prognosis in obesity. Monocytes are main sources of cytokines and play a pivotal role in inflammation. We evaluated monocyte frequency, phenotype and cytokine profile of monocyte subsets, to determine their association with the pathogenesis of childhood obesity. Children with obesity were evaluated for biochemical and anthropometric parameters. Monocyte subsets were characterized by flow cytometry, considering cytokine production and activation/recognition molecules. Correlation analysis between clinical parameters and immunological data delineated the monocytes contribution for low-grade inflammation. We observed a higher frequency of non-classical monocytes in the childhood obesity group (CO) than normal-weight group (NW). All subsets displayed higher TLR4 expression in CO, but their recognition and antigen presentation functions seem to be diminished due to lower expression of CD40, CD80/86 and HLA-DR. All subsets showed a lower expression of IL-10 in CO and correlation analyses showed changes in IL-10 expression profile. The lower expression of IL-10 may be decisive for the maintenance of the low-grade inflammation status in CO, especially for alterations in non-classical monocytes profile. These cells may contribute to supporting inflammation and loss of regulation in the immune response of children with obesity.