Alterações funcionais induzidas por células trofoblásticas em monócitos infectados por Toxoplasma gondii

Abstract

Toxoplasma gondii is an intracellular parasite that can infect humans and cause toxoplasmosis. This pathogenesis is potentially severe in immunocompromised individuals and during pregnancy because congenital infection can adversely affect both the gestation and normal development of the embryo. During pregnancy, trophoblast cells constitute an important maternal-fetal barrier and innate immune cells, such as monocytes, concentrate around them. Thus, interactions between trophoblast cells and monocytes are important to maintain the normal course of pregnancy, especially in situations of infection. This study aimed to evaluate if trophoblast cells (BeWo cell line) modulate the functional activity of monocytes (THP-1 cell line) in the presence or absence of T. gondii infection. The perfil of cytokines (MIF, IL-12, IL-6, IL-17A, TGF-β1 e IL-10) secreted by THP-1 and BeWo cells was characterized and both of the cell lines show profile of pro-inflammatory cytokines after the infection. Furthermore, THP-1 cells were stimulated with supernatants of BeWo cells previously infected or not with T. gondii and, after this, THP-1 cells were infected with T. gondii. The secretion of cytokines by THP-1 cells was then evaluated, as well as the susceptibility of these cells to T. gondii infection. The results demonstrated that the supernatant of infected BeWo cells induced non-infected THP-1 cells to secret higher levels of pro-inflammatory cytokines and the supernatant of non-infected BeWo cells decreased the secretion of MIF, increased the secretion of IL-6 and not altered the secretion of IL-12 and IL- 17 by these THP-1 cells. Furthermore, both of the supernatants induced lower secretion of MIF and IL-12 and higher secretion of IL-6 by THP-1 cells infected with T. gondii. The secretion of IL-17 by infected THP-1 cells was higher only with stimuli of infected BeWo cells. The secretion of TGF-β1 by THP-1 cells stimulated with the supernatants of uninfected or infected BeWo cells was down-modulated while the secretion of IL-10, in the same conditions, was up-modulated. In addition, THP-1 cells stimulated, principally with the supernatants of previously infected BeWo cells, were more resistant to T. gondii proliferation. THP-1 cells treated with rIL-6 were less permissive to T. gondii proliferation and in the absence of this cytokine, this parasite proliferation increased. Thus, the secretion of IL-6 by THP-1 cells is involved in the control of T. gondii infection. Additionally, the secretion of IL- 6 and MIF by BeWo cells, but not the secretion of TGF-β1, was important to control the parasitism in THP-1 cells. Together, these results suggest that trophoblast cells are able to modulate the activity of monocytes and it is associated with the control and maintenance of pregnancy.