Departamento de Sanidad Animal. Facultad de Veterinaria. Universidad de León. Campus De Vegazana s/n, 24071, León, Spain; Instituto de Ganadería de Montaña. (CSIC-Universidad de León). Grulleros, 24346, León, Spain.
Laboratorio de Parasitología. Centro de Investigaciones Agrarias de Mabegondo, AGACAL-Xunta de Galicia. Ctra. Betanzos a Mesón do Vento km 7, Abegondo, 15318, A Coruña, Spain.
Vet Parasitol. 2020 Sep;285:109204. doi: 10.1016/j.vetpar.2020.109204. Epub 2020 Aug 18.
In order to gain further insight into the pathogenesis and transmission of ovine neosporosis, the serological response of 13 naturally infected pregnant sheep was monitored. All sheep were euthanized upon the detection of a sharp increase in the level of specific antibodies against N. caninum in order to study the maternal immune response after the recrudescence of a chronic infection. Ten sheep were euthanized between 84 and 118 days of gestation, whereas the three remaining and three control not infected, pregnant sheep were euthanized at 135 days of gestation after no sharp increase in antibodies was detected. Vertical transmission was confirmed in 11 sheep by detection of N. caninum-DNA in at least one fetus, confirming recrudescence. Not all of fetuses showed pathologic microscopic lesions, however, multifocal non-purulent encephalitis was the main finding. Furthermore, nine out of the 11 vertical transmission positive sheep had lesions in placentomes (mainly multifocal necrotic foci), and the parasite was detected in eight out of 11 placentas by PCR and/or immunohistochemestry. The placentomes from sheep that suffered recrudescence showed an increased number of T lymphocytes CD3+ (CD4/CD8 < 1) and macrophages (MHC-II+), assessed by immunohistochemestry, together with an up-regulation of IFN-γ, IL-10, IL-4, TNFα, IL-2 and IL-18. IL-17 was only upregulated in the three infected sheep that did not have a sharp increase in antibody levels. In the sheep that showed fetal death at the time of euthanasia (n = 3) the placental microscopic lesions were more severe, the inflammatory infiltrate was higher, and the upregulation of cytokines was greater than in those sheep carrying viable fetuses. This study suggests that, similarly to bovine neosporosis, the time of gestation when recrudescence occurs determines the viability of the fetuses and, thus, seems to be related to the severity of lesions and immune response in the placenta. These results suggest that there might be a correlation, either as cause or as a consequence, between protection against vertical transmission of the parasite and a milder maternal serological response together with a high level of transcription of IL-17 in the placenta.
为了深入了解绵羊新孢子虫病的发病机制和传播途径，监测了 13 只自然感染的怀孕绵羊的血清反应。所有绵羊在特异性抗体水平对 N. caninum 的急剧增加检测到后被安乐死，以便研究慢性感染复发后的母性免疫反应。10 只绵羊在妊娠 84 至 118 天之间被安乐死，而其余 3 只未感染的对照怀孕绵羊在抗体无明显增加的情况下于 135 天被安乐死。通过至少一个胎儿中检测到 N. caninum-DNA ，证实了 11 只绵羊的垂直传播，证实了复发。然而，并非所有胎儿都表现出病理微观病变，而是主要发现多灶性非化脓性脑炎。此外，在 11 只垂直传播阳性的绵羊中，有 9 只胎盘瘤（主要是多灶性坏死灶）有病变，通过 PCR 和/或免疫组织化学检测到寄生虫在 11 个胎盘中有 8 个。在复发的绵羊中，胎盘瘤中的 T 淋巴细胞 CD3+（CD4/CD8<1）和巨噬细胞（MHC-II+）数量增加，通过免疫组织化学评估，与 IFN-γ、IL-10、IL-4、TNFα、IL-2 和 IL-18 的上调有关。仅在 3 只未出现抗体水平急剧增加的感染绵羊中上调了 IL-17。在安乐死时发生胎儿死亡的绵羊中（n=3），胎盘的微观病变更严重，炎症浸润更高，细胞因子的上调大于携带存活胎儿的绵羊。这项研究表明，与牛新孢子虫病类似，复发发生的妊娠时间决定了胎儿的存活能力，因此似乎与胎盘的病变严重程度和免疫反应有关。这些结果表明，寄生虫垂直传播的保护作用与胎盘中 IL-17 的轻度母性血清反应和高水平转录之间可能存在相关性，无论是作为原因还是结果。
