Department of Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei, People's Republic of China.
Parasitol Res. 2013 Aug;112(8):3019-27. doi: 10.1007/s00436-013-3475-3. Epub 2013 May 31.
Toxoplasma gondii is an apicomplexan parasite capable of transplacental transmission to cause spontaneous abortion or significant disease in the surviving neonate. Different from the dominant genotypes of T. gondii strains in European and North American which belong to three distinct clonal lineages, type I, type II, and type III, isolates from China possess the predominant genotype of China 1(ToxoDB#9) with a different virulence. The genotype-associated pathogenesis has been investigated previously. Based on two isolates of T. gondii from Chinese wild cats, a murine model of pregnancy and one transwell system in vitro, here we reported differentially polarized activation of macrophages induced by genotype China 1 strains, TgCtwh3 and TgCtwh6 with different virulence to mice, and its impact on trophoblast apoptosis. The results showed that macrophages were alternatively activated when infected with virulent TgCtwh3 while classically activated when infected with low virulent (cyst-forming) TgCtwh6 both in vitro and in vivo. By the analysis of flow cytometry, the percentage of the Th1 cells in two infection groups decreased significantly, and the Th2 cells from spleen escalated only in the virulent TgCtwh3 group. Interestingly, the high parasite burden was noted in the placenta of TgCtwh3-infected group whereas the inflammatory cells infiltration predominates in the TgCtwh6-infected group. In vivo trophoblast apoptosis in TgCtwh3 group was found to be more obvious when compared with TgCtwh6 although it was present in both. The present observations indicate that polarization of macrophages and modulation of Th subsets induced by the isolates with identical genotype but different virulence could contribute to trophoblast apoptosis through different mechanisms, suggesting a virulence-associated pathogenesis of T. gondii in abnormal pregnant outcome.
刚地弓形虫是一种顶复门寄生虫，能够通过胎盘传播，导致自然流产或存活的新生儿出现严重疾病。与欧洲和北美优势的弓形虫株基因型不同，属于三个不同的克隆谱系，即 I 型、II 型和 III 型，来自中国的分离株具有主要基因型中国 1（ToxoDB#9），具有不同的毒力。基因型相关的发病机制此前已被研究过。基于来自中国野生猫的两种弓形虫分离株，一个妊娠的小鼠模型和一个体外 Transwell 系统，我们在这里报道了基因型中国 1 株 TgCtwh3 和 TgCtwh6 诱导的巨噬细胞极化的差异激活，这两种株具有不同的对小鼠的毒力，及其对滋养层细胞凋亡的影响。结果表明，在体外和体内，毒力较强的 TgCtwh3 感染时巨噬细胞被交替激活，而低毒力（形成囊肿）的 TgCtwh6 感染时巨噬细胞被经典激活。通过流式细胞术分析，两组感染中 Th1 细胞的比例显著下降，只有在毒力较强的 TgCtwh3 组中，脾中的 Th2 细胞增加。有趣的是，在 TgCtwh3 感染组中观察到胎盘内寄生虫负荷较高，而在 TgCtwh6 感染组中炎症细胞浸润为主。与 TgCtwh6 相比，TgCtwh3 感染组的体内滋养层细胞凋亡更为明显，尽管两者都存在。这些观察结果表明，具有相同基因型但不同毒力的分离株诱导的巨噬细胞极化和 Th 亚群的调节可能通过不同的机制导致滋养层细胞凋亡，提示弓形虫在异常妊娠结局中的毒力相关发病机制。
