Barbosa B F, Silva D A O, Costa I N, Mineo J R, Ferro E A V
Laboratory of Histology and Embryology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, MG, Brazil.
Clin Exp Immunol. 2008 Mar;151(3):536-45. doi: 10.1111/j.1365-2249.2007.03583.x.
The present study aimed to investigate BeWo trophoblast cell susceptibility to Toxoplasma gondii infection under stimulation with anti-inflammatory cytokines in comparison with HeLa cells. Both cell types were submitted to different treatments with recombinant cytokines [interleukin (IL)-10 and transforming growth factor (TGF)-beta1] or the respective antibodies (anti-IL-10 and anti-TGF-beta) before and after T. gondii infection. The effect of interferon (IFN)-gamma was also assessed alone or in combination with anti-inflammatory cytokines or the respective antibodies after the parasite infection. Cells were fixed, stained and parasites quantified under light microscopy to evaluate intracellular replication (mean number of parasites per cell in 100 infected cells) and infection index (percentage of infected cells per 100 examined cells). In contrast with HeLa cells, treatments with IL-10 or TGF-beta1 induced a considerable augmentation in both T. gondii intracellular replication and invasion into BeWo cells. In addition, treatment with IFN-gamma alone or associated with IL-10 or TGF-beta1 increased the same parameters in BeWo cells, whereas the opposite effect was observed in HeLa cells. When endogenous IL-10 or TGF-beta was blocked, both BeWo and HeLa cells were able to control the parasite infection only in the presence of IFN-gamma. Together, these results indicate that the higher susceptibility of BeWo cells to T. gondii may be due to immunomodulation mechanisms, suggesting that the role of trophoblast cells in maintaining a placental microenvironment favourable to pregnancy may facilitate the infection into the placental tissues.
本研究旨在调查与HeLa细胞相比,在抗炎细胞因子刺激下BeWo滋养层细胞对刚地弓形虫感染的易感性。在刚地弓形虫感染之前和之后,两种细胞类型都接受了重组细胞因子[白细胞介素(IL)-10和转化生长因子(TGF)-β1]或相应抗体(抗IL-10和抗TGF-β)的不同处理。在寄生虫感染后,还单独或与抗炎细胞因子或相应抗体联合评估了干扰素(IFN)-γ的作用。细胞经固定、染色后,在光学显微镜下对寄生虫进行定量,以评估细胞内复制(100个感染细胞中每个细胞内寄生虫的平均数)和感染指数(每100个检查细胞中感染细胞的百分比)。与HeLa细胞相反,用IL-10或TGF-β1处理会导致刚地弓形虫在BeWo细胞内的复制和侵入均显著增加。此外,单独用IFN-γ处理或与IL-10或TGF-β1联合处理会使BeWo细胞中的相同参数增加,而在HeLa细胞中观察到相反的效果。当内源性IL-10或TGF-β被阻断时,只有在存在IFN-γ的情况下,BeWo和HeLa细胞才能控制寄生虫感染。总之,这些结果表明,BeWo细胞对刚地弓形虫较高的易感性可能归因于免疫调节机制,这表明滋养层细胞在维持有利于妊娠的胎盘微环境中的作用可能会促进对胎盘组织的感染。