Department of Pathogen Biology, Key Laboratory of Pathogen Biology of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, China.
PLoS One. 2013 Jul 17;8(7):e69012. doi: 10.1371/journal.pone.0069012. Print 2013.
Toxoplasma gondii is an opportunistic intracellular parasite that is highly prevalent in human and warm-blooded animals throughout the world, leading to potentially severe congenital infections. Although the abortion caused by T. gondii is believed to be dependent on the timing of maternal infection during pregnancy, the mechanism remains unclear. This study was focused on the effects of T. gondii excreted-secreted antigens on pregnant outcomes and CD4(+)CD25(+) Foxp3(+) regulatory T cells at different stages of pregnancy. The results showed that in mice the frequency and suppressive function of CD4(+)CD25(+) regulatory cells were diminished after injection of T. gondii excreted-secreted antigens at early and intermediate stages of pregnancy. The abortion caused by T. gondii excreted-secreted antigens at early pregnancy could be partly prevented by adoptively transferring of CD4(+)CD25(+) cells from the mice injected with T. gondii excreted-secreted antigens at late pregnancy, but not from the mice with the same treatment at early pregnancy. Furthermore, T. gondii excreted-secreted antigens induced apoptosis of CD4(+)CD25(+) regulatory cells of mice in early and intermediate stages of pregnancy by down-regulating their Bcl-2 expressions and Bcl-2/Bax ratio. This study provides new insights into the mechanism that T. gondii infection is the high risk factor for abortion in early pregnancy.
刚地弓形虫是一种机会性细胞内寄生虫,在全球范围内广泛存在于人和温血动物中,可能导致严重的先天性感染。虽然认为弓形虫引起的流产取决于母体在怀孕期间感染的时间,但机制尚不清楚。本研究集中研究了弓形虫排泄-分泌抗原对妊娠不同阶段妊娠结局和 CD4+CD25+Foxp3+调节性 T 细胞的影响。结果表明,在怀孕早期和中期注射弓形虫排泄-分泌抗原后,小鼠 CD4+CD25+调节性细胞的频率和抑制功能降低。用来自怀孕晚期注射弓形虫排泄-分泌抗原的小鼠的 CD4+CD25+细胞而非来自怀孕早期相同处理的小鼠的 CD4+CD25+细胞的过继转移,可以部分预防弓形虫排泄-分泌抗原引起的早期妊娠流产。此外,弓形虫排泄-分泌抗原通过下调其 Bcl-2 表达和 Bcl-2/Bax 比值,诱导妊娠早期和中期的 CD4+CD25+调节性细胞凋亡。本研究为弓形虫感染是早期妊娠流产的高危因素的机制提供了新的见解。