National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
Division of Pathobiological Science, Department of Basic Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
Infect Immun. 2021 Jan 19;89(2). doi: 10.1128/IAI.00253-20.
Toxoplasmosis is a worldwide zoonosis caused by the obligate intracellular parasite The symptoms of congenital toxoplasmosis range from embryonic death and resorption to subclinical infection, but the mechanism of disease onset remains unclear. C-X-C motif chemokine receptor 3 (CXCR3) is highly expressed in Th1-associated immune cells and plays an important role in the trafficking and activation of immune cells. However, the roles of CXCR3 in -induced fetal loss and the molecular mechanism of embryo resorption remain poorly understood. In this study, we investigated the role of CXCR3 in fetal wastage caused by infection using CXCR3-deficient (CXCR3) mice. CXCR3 and wild-type pregnant mice were inoculated intraperitoneally with tachyzoites on day 3.5 of gestation (Gd3.5). Pregnancy rates decreased as the pregnancy progressed in both infected groups; however, infected CXCR3 mice showed a significant fetal loss at Gd13.5 compared with that at Gd7.5. All embryos of the infected groups showed necrosis, and embryo resorption was significantly increased in infected CXCR3 compared with wild-type mice at Gd13.5. The parasite load of fetoplacental tissues was significantly increased in CXCR3 mice at Gd10.5. Moreover, mRNA expression levels of inducible nitric oxide synthase were significantly increased in fetoplacental tissues from infected wild-type mice compared to infected CXCR3 mice following the infection. These results suggested that CXCR3-dependent immune responses provide anti- activity and play an essential role in reducing embryo resorption and fetal loss caused by infection during early pregnancy.
弓形虫病是一种全球性的动物传染病，由专性细胞内寄生虫弓形虫引起。先天性弓形虫病的症状范围从胚胎死亡和吸收到亚临床感染，但疾病发病机制仍不清楚。C-X-C 基序趋化因子受体 3（CXCR3）在 Th1 相关免疫细胞中高度表达，在免疫细胞的迁移和激活中发挥重要作用。然而，CXCR3 在弓形虫感染导致的胎儿丢失中的作用及其导致胚胎吸收的分子机制尚不清楚。在这项研究中，我们使用 CXCR3 缺陷（CXCR3）小鼠研究了 CXCR3 在弓形虫感染引起的胎儿丢失中的作用。CXCR3 和野生型怀孕小鼠在妊娠第 3.5 天（Gd3.5）经腹腔接种速殖子。在两个感染组中，随着妊娠的进展，妊娠率均下降；然而，与 Gd7.5 相比，感染 CXCR3 的小鼠在 Gd13.5 时表现出明显的胎儿丢失。所有感染组的胚胎均出现坏死，与野生型小鼠相比，感染 CXCR3 的小鼠在 Gd13.5 时胚胎吸收明显增加。Gd10.5 时，CXCR3 小鼠胎盘中的寄生虫负荷明显增加。此外，与感染 CXCR3 的小鼠相比，感染野生型小鼠的胎盘中诱导型一氧化氮合酶的 mRNA 表达水平在感染后显著增加。这些结果表明，CXCR3 依赖性免疫反应提供了抗寄生虫活性，并在减少早期妊娠弓形虫感染引起的胚胎吸收和胎儿丢失方面发挥了重要作用。
