Análise da expressão das metaloproteinases 2 e 9 e do perfil de citocinas produzidas em neutrófilos e monócitos de pacientes portadores da doença de Chagas

Abstract

Chagas disease, caused by Trypanosoma cruzi infection, is a serious problem for public health in Latin America. The increase of migration of patients infected by T.cruzi in recent years allowed the disease to reach the non-endemic regions, thereby increasing worldwide concern for control measures. After the acute phase, the chronic disease is established and different clinical forms may develop. Most of patients present no symptoms due to infection and are classified as indeterminate clinical form (IND). In contrast, about 30% of patients present mild to severe cardiac abnormalities, ranked with cardiac clinical form (CARD). Chagas cardiomyopathy is characterized by a myocardial remodeling and interstitial fibrosis, resulting in changes of extracellular matrix (ECM). Proteolytic enzymes such as matrix metalloproteinases (MMPs) and cytokines are able to control ECM degradation and synthesis processes. These proteins are produced by different cells, including innate immune cells. This study aimed to characterize the levels of MMP-2 and MMP-9, which are involved in cardiac remodeling, and the cytokines IL-1, IL-10, TGF-, TNF- in neutrophils and monocytes, as well the serum levels of MMPs and their inhibitors in patients with Chagas disease. The results showed that neutrophils and monocytes from chagasic patients have higher levels of MMP-9 and MMP-2 levels after in vitro stimulation with T. cruzi antigens. IL-1, TGF-and TNF- are significantly higher in neutrophils from CARD patients, while IL-10 is increased in neutrophils from IND patients. For monocytes, TNF- showed a significant increase in infected patients before and after stimulation with T. cruzi antigens. MMP-2 presented positively correlated with IL-10 and negative correlation with IL-1. Moreover, MMP-9 was positively correlated with IL-1. Levels of MMPs 2 and 9, as well as their inhibitors (TIMPs), were also evaluated in serum samples. The results showed an increase in seric levels of TIMP-2, MMP-2 and MMP-9 in CARD group. We observed a negative correlation between MMP-2 and MMP- 9 with TIMP-1 in the CARD group and a positive correlation between TIMPs and a negative correlation between MMPs, both in IND group. The results suggest the same behavior between neutrophils and monocytes concerning the production of MMP-2 and MMP-9 in the different clinical forms of the disease. It suggests that these innate cells may be involved in an important pathway of fibrosis induction in the chagasic cardiomyopathy context.