Associação da expressão do fator de necrose tumoral α (TNF-α) e seus receptores na infecção de células placentárias humanas por formas tripomastigotas de Trypanosoma cruzi

Abstract

Chagas disease is a neglected tropical disease, caused by the protozoan Trypansoma cruzi and endemic in Latin America. The modes of transmission include vectorial, through blood transfusion, oral or congenital. Congenital transmission is the main form of transmission in non- endemic countries, with an increase in the number of cases due to migration of woman of gestational age from endemic countries. The drugs utilized during Chagas disease treatment are not recommended for pregnant women, therefore, currently there are no methods of preventing congenital transmission. The T. cruzi population that infects humans is classified into Discrete Typing Units (DTUs), ranging from TcI to TcV and are associated with distinct biological and clinical characteristics, and to congenital transmission. Regions where infection occurs predominantly with strains belonging to TcII present lower maternal-fetal transmission rates, while regions where infection occurs mainly with TcV have higher transmission rates. Studies with the 3253 strain, belonging to TcV have shown that this strain can induce higher levels of the pro-inflammatory cytokine TNF and higher TNF/IL10 rates in human monocytes in vitro, besides showing higher infection rates in the trophoblastic BeWo cells than the Y strain, which belongs to TcII. Therefore, the hypothesis tested in this work is that the infection with T. cruzi leads to higher production of TNF as well as its receptors in human trophoblastic cells, and that higher production of this cytokine results in higher infection in these cells. For this purpose, the infection rates, expression of TNF and its receptors and of the anti-inflammatory cytokine IL- 10 was evaluated in BeWo cells, syncicialized or not and exposed to the 3253 and Y strains. These parameters were evaluated in the presence or absence of pentoxifylline, a drug which inhibits the effects of TNF. Our results show a higher intensity of infection in non-syncicialized BeWo cells by the Y strain, while the 3253 strain was able to infect the cells with higher intensity after syncicialization. Treatment with the drug increased intensity of infection by the Y strain in syncicialized BeWo cells. Infection with both strains induced an increase in TNFr2 expression, with higher expression observed with the Y strain rather than the 3253 strain. High intensities of infection also induced an increase in TNF and IL-10 expression. In some uninfected populations and those infected with the 3253 strain, 16-hour treatment with the drug led to reduced TNF expression, while 4-hour treatment reduced TNFr2 in uninfected cells. Infection with 3253 also induced an increase in IL-6 and IL-8 expression, while the Y strain led to a decrease in IL-6 expression. Treatment with PTX resulted in reduced expression of both cytokines. The results show the involvement of TNFr2 in the infection of trophoblastic cells with T. cruzi and that pentoxifylline treatment increased syncicialized BeWo infection with the Y strain, but not with the 3253 strain. Our results show that different T. cruzi isolates interact differently with human placental cells and respond distinctively to treatment with PTX.