Associação entre subpopulações de monócitos e Linfócitos T CD4+ nas diferentes formas clínicas da Doença de Chagas

Abstract

Although Chagas disease, caused by the protozoan Trypanosoma cruzi, was discovered in 1909, it remains a serious public health problem in many countries. It is estimated that currently there are 8 million people infected in the world, mainly in 21 countries in Latin America where the disease is endemic. Increased morbidity in non-endemic regions has received great attention today, mainly due to the migration of infected individuals, becoming Chagas disease a serious epidemiological, economic and social problem at a global level. Chagas disease is characterized by two distinct phases during its course: the acute phase with short duration shows high parasitism and parasitemia, and the chronic phase, in which about 60% of the affected individuals may not develop specific clinical symptoms of the disease and are clinically classified as with the indeterminate clinical form (IND). However, 30% of these individuals develop cardiac alterations resulting from progressive myocardial damage that may lead to chagasic cardiomyopathy, classified as with the cardiac clinical form (CARD). The study of innate and adaptive immunity is of great importance for the understanding of this disease. The interaction between monocytes and lymphocytes may be an important point to help to clarify the complexity that surrounds the clinical manifestations of the chronic phase of Chagas disease. Although many studies have contributed to the understanding of the pathophysiology of Chagas disease, the mechanisms that explain the evolution to the cardiac form of the disease and the distinction of the clinical manifestations have not yet been fully established. The present work aimed to evaluate the association between the monocyte subsets: classical (CD14+CD16- ), intermediates (CD14+CD16+ ) and non-classical (CD14- CD16+ ) and the different CD4+ T lymphocytes subsets (Th1, Th2, Th17, Treg), after in vitro stimulation with T. cruzi antigens, in peripheral blood cells of individuals in the different clinical forms of Chagas disease. Our results showed a significant increase in the expression of the co-stimulatory molecule CD80 in classic monocytes in the CARD group and CD86 in non-classical monocytes in the IND group. Using linear regression analysis a significant association between non-classical CD86+ monocytes and Treg lymphocytes was observed in non-infected (NI), IND and CARD groups. A significant increase in the frequency of Treg IL10+ IL-17+ lymphocytes in the IND group was observed when compared to the CARD group after stimulation with T.cruzi was observed. These results suggest that CD86+ monocytes preferentially target a Treg response independent of the evaluated group, presenting in greater abundance in IND patients, favoring the formation of a more regulated environment and limiting the development of the disease in these patients. In contrast, CARD patients besides directing a response mediated by Th1 lymphocytes, present Treg cell activation through the alternative interaction with CD80 of the monocytes, suggesting that this interaction is inefficient in regulating the immune response, contributing to the maintenance of the persistent inflammatory process as observed in these patients.