Role of dense granule antigen 7 in vertical transmission of Neospora caninum in C57BL/6 mice infected during early pregnancy
Role of dense granule antigen 7 in vertical transmission of Neospora caninum in C57BL/6 mice infected during early pregnancy
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DOI：
10.1016/j.parint.2022.102576
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发表时间：
2022-03-25
影响因子：
1.9
通讯作者：
Nishikawa, Yoshifumi
中科院分区：
文献类型：
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作者：
Abdou, Ahmed M.;Ikeda, Rina;Nishikawa, Yoshifumi
新孢子虫病是一种寄生虫病，影响全球犬和牛的健康。它是由犬新孢子虫引起的，一种专性细胞内顶复寄生虫。犬是其最终宿主，主要感染家畜，尤其是牛作为中间宿主。因此，必须建立实验动物的流产和垂直传播模型，以确定防治的基本措施。犬感染我们评估了N.犬致密颗粒抗原7（NcGRA 7）在猪纳氏线虫垂直传播中的作用。使用C57 BL/6妊娠小鼠模型。我们在妊娠第3.5天用亲本Nc-1或NcGRA 7缺陷型寄生虫（NcGRA 7 KO）接种小鼠。在出生后第30天进行尸检分析，并将存活幼仔保留至产后第30天。在两种感染剂量（1 × 10（6）和1 × 10（5）速殖子/小鼠）下，NcGRA 7 KO感染母鼠后代脑组织中的寄生虫数量显著低于Nc-1感染母鼠。NcGRA 7 KO感染组的垂直传播率显著低于Nc 1感染组。为了理解NcGRA 7的缺乏降低垂直传播的机制，在妊娠第13.5天（感染后10天）处死妊娠小鼠，尽管在胎盘中检测到寄生虫DNA，但在两种寄生虫系之间没有发现显著差异。组织学分析显示，NcGRA 7 KO感染母鼠的胎盘中的炎症反应比亲本菌株的胎盘中的炎症反应更大。这一发现与NcGRA 7 KO感染小鼠胎盘中CCL 2、CCL 8和CXCL 9的趋化因子mRNA表达上调相关。总之，这些结果表明，NcGRA 7的丢失触发了胎盘中的炎症反应，导致N.犬的
Neosporosis is a parasitic disease affecting the health of dogs and cattle worldwide. It is caused by Neospora caninum, an obligate intracellular apicomplexan parasite. Dogs are its definitive host, it mostly infects livestock animals, especially cattle that acts as intermediate host. It is necessary to have well-established models of abortion and vertical transmission in experimental animals, in order to determine basic control measures for the N. caninum infection. We evaluated the role of N. caninum dense granule antigen 7 (NcGRA7) in the vertical transmission of N. caninum using the C57BL/6 pregnant mouse model. We inoculated mice on day 3.5 of pregnancy with parental Nc-1 or NcGRA7-deficient parasites (NcGRA7KO). Post-mortem analyses were performed on day 30 after birth and the surviving pups were kept until day 30 postpartum. The number of parasites in the brain tissues of offspring from NcGRA7KO-infected dams was significantly lower than that of the Nc-1-infected dams under two infection doses (1 x 10(6) and 1 x 10(5) tachyzoites/mouse). The vertical transmission rates in the NcGRA7KO-infected group were significantly lower than those of the Nc1-infected group. To understand the mechanism by which the lack of NcGRA7 decreases the vertical transmission, pregnant mice were sacrificed on day 13.5 of pregnancy (10 days after infection), although parasite DNA was detected in the placentas, no significant difference was found between the two parasite lines. Histopathological analysis revealed a greater inflammatory response in the placentas from NcGRA7KO-infected dams than in those from the parental strain. This finding correlates with upregulated chemokine mRNA expression for CCL2, CCL8, and CXCL9 in the placentas from the NcGRA7KO-infected mice. In conclusion, these results suggest that loss of NcGRA7 triggers an inflammatory response in the placenta, resulting in decreased vertical transmission of N. caninum.