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Identification and Characterization of Neospora caninum Cyclophilin That Elicits Gamma Interferon Production

机译:Neospora Caninum Cellophilin的鉴定与表征,其引起γ干扰素生产

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Gamma interferon (IFN-γ) response is essential to the development of a host protective immunity in response to infections by intracellular parasites. Neosporosis, an infection caused by the intracellular protozoan parasite Neospora caninum, is fatal when there is a complete lack of IFN-γ in the infected host. However, the mechanism by which IFN-γ is elicited by the invading parasite is unclear. This study has identified a microbial protein in the N. caninum tachyzoite N. caninum cyclophilin (NcCyP) as a major component of the parasite responsible for the induction of IFN-γ production by bovine peripheral blood mononuclear cells (PBMC) and antigen-specific CD4+ T cells. NcCyP has high sequence homology (86%) with Toxoplasma gondii 18-kDa CyP with a calculated molecular mass of 19.4 kDa. NcCyP is a secretory protein with a predicted signal peptide of 17 amino acids. Abundant NcCyP was detected in whole-cell N. caninum tachyzoite lysate antigen (NcAg) and N. caninum tachyzoite culture supernatant. In N. caninum tachyzoite culture supernatant, three NcCyP bands of 19, 22, and 24 kDa were identified. NcAg stimulated high levels of IFN-γ production by PBMC and CD4+ T cells. The IFN-γ-inducing effect of NcAg was blocked by cyclosporine, a specific ligand for CyP, in a dose-dependent manner. Furthermore, cyclosporine abolished IFN-γ production by PBMC from na?ve cows as well as PBMC and CD4+ T cells from infected/immunized cows. These results indicate that the N. caninum tachyzoite naturally produces a potent IFN-γ-inducing protein, NcCyP, which may be important for parasite survival as well as host protection.
机译:γ干扰素(IFN-γ)反应对于响应细胞内寄生虫的感染而对宿主保护性豁免的发展至关重要。新孢子症,由细胞内原生动物寄生虫引起的感染 Neospora caninum ,当感染宿主中完全缺乏IFN-γ时,是致命的。然而,IFN-γ由入侵寄生虫引发的机制尚不清楚。该研究鉴定了 N中的微生物蛋白。 caninum tachyzoite n。 Caninum Cellophilin(Nccyp)作为寄生物质的主要成分,负责牛外周血单核细胞(PBMC)和抗原特异性CD4 + T细胞的IFN-γ产生。 Nccyp具有高序列同源性(86%),具有弓形虫Gondii 18-KDA CYP,其计算分子量为19.4kDa。 Nccyp是一种分泌蛋白,具有17个氨基酸的预测信号肽。在全细胞 N中检测到丰富的Nccyp。 Caninum Tachyzoite裂解物抗原(ncag)和 n。 Caninum Tachyzoite培养上清液。在 n。鉴定了Caninum Tachyzoite培养上清液,鉴定了19,22和24kDa的三个Nccyp条带。 NCAG通过PBMC和CD4 + T细胞刺激高水平的IFN-γ产生。 NCAG的IFN-γ-诱导效应通过环孢菌素,CYP的特定配体抑制,以剂量依赖性方式阻断。此外,通过来自NaαVe奶牛的PBMC以及来自感染/免疫奶牛的PBMC和CD4 + / sup> T细胞,CycroSporine废除IFN-γ产生。这些结果表明 n。 Caninum Tachyzoite天然产生强大的IFN-γ诱导蛋白,NcCyp,这对于寄生物存活以及宿主保护可能是重要的。

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