ISP, INRA, Université Tours, 37380 Nouzilly, France.
Institut für Virologie, AG Parasitologie, Philipps-Universität Marburg, 35043 Marburg, Germany.
Cytokine. 2019 Jul;119:119-128. doi: 10.1016/j.cyto.2019.03.014. Epub 2019 Mar 23.
Neosporosis due to Neospora caninum causes abortions in farm animals such as cattle. No treatment and vaccine exist to fight this disease, responsible for considerable economic losses. It is thus important to better understand the immune responses occurring during the pathogenesis to control them in a global strategy against the parasite. In this context, we studied the roles of N. caninum glycosylphosphatidylinositols (GPIs), glycolipids defined as toxins in the related parasite Plasmodium falciparum. We demonstrated for the first time that GPIs could be excreted in the supernatant of N. caninum culture and trigger cell signalling through the Toll-like receptors 2 and 4. In addition, antibodies specific to N. caninum GPIs were detected in the serum of infected mice. As shown for other protozoan diseases, they could play a role in neutralizing GPIs. N. caninum GPIs were able to induce the production of tumour necrosis factor-α, interleukin(IL)-1β and IL-12 cytokines by murine macrophages and dendritic cells. Furthermore, GPIs significantly reduced expression of major histocompatibility complex (MHC) molecules of class I on murine dendritic cells. In contrast to murine cells, bovine blood mononuclear cells produced increased levels of IFN-γ and IL-10, but reduced levels of IL-12p40 in response to GPIs. On these bovine cells, GPI had the tendency to up-regulate MHC class I, but to down-regulate MHC class II. Altogether, these results suggest that N. caninum GPIs might differentially participate in the responses of antigen presenting cells induced by the whole parasite in mouse models of neosporosis and in the natural cattle host.
刚地弓形虫引起的刚地弓形虫病可导致牛等家畜流产。目前尚无治疗和疫苗来对抗这种疾病，它给畜牧业造成了巨大的经济损失。因此，深入了解发病过程中的免疫反应，并以此为基础制定出控制寄生虫的全球策略非常重要。在这一背景下，我们研究了刚地弓形虫糖基磷脂酰肌醇（GPIs）在寄生虫发病机制中的作用。GPIs 是相关寄生虫疟原虫中的毒素，我们首次证明，GPIs 可从刚地弓形虫培养物上清液中分泌，并通过 Toll 样受体 2 和 4 触发细胞信号转导。此外，在感染小鼠的血清中检测到针对刚地弓形虫 GPIs 的特异性抗体。与其他原生动物疾病一样，这些抗体可能在中和 GPIs 方面发挥作用。刚地弓形虫 GPIs 能够诱导鼠巨噬细胞和树突状细胞产生肿瘤坏死因子-α、白细胞介素-1β和白细胞介素-12。此外，GPIs 可显著降低鼠树突状细胞主要组织相容性复合体（MHC）I 类分子的表达。与鼠细胞不同，牛血液单核细胞在受到 GPIs 刺激时会产生更高水平的 IFN-γ和 IL-10，但 IL-12p40 水平降低。在这些牛细胞上，GPI 有上调 MHC I 类的趋势，但下调 MHC II 类的趋势。综上所述，这些结果表明，刚地弓形虫 GPIs 可能在刚地弓形虫病的鼠模型和天然牛宿主中，通过整个寄生虫诱导的抗原呈递细胞反应中发挥不同的作用。
