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编码利什曼原虫感染因子(LeIF)基因和白细胞介素-12(IL-12)的DNA疫苗共递送可增强BALB/c小鼠对硕大利什曼原虫感染的抵抗力。

Codelivery of DNA vaccination encoding LeIF gene and IL-12 increases protection against Leishmania major infection in BALB/c mice.

作者信息

Maspi N, Ghaffarifar F, Sharifi Z, Dalimi A

机构信息

Department of Medical Parasitology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.

出版信息

Parasite Immunol. 2016 Apr;38(4):228-35. doi: 10.1111/pim.12310.

Abstract

Previous studies have shown that Leishmania elongation initiation factor (LeIF) antigen causes a partial immunity against leishmaniasis. The antigen develops type I immunity by overexpression of inflammatory cytokines such as interleukin-12 (IL-12), IFN-γ and TNF-α. Therefore, We evaluated immune responses induced by the LeIF gene against Leishmania major infection. Immunization with LeIF gene alone or with IL-12 induced Th1 response and produced higher IFN-γ and lower IL-4 levels by splenocytes than control groups (P < 0·05) and also ratios of IFN-γ/IL-4 were 11·68 to 18·53 times more in immunized groups than control groups after challenge. In addition, analysis of humoral immune response revealed that immunized mice had more IgG2a levels than both control groups (P < 0·05). On the other hand, lesion size was less for immunized animals than control groups from 4th week after challenge (P < 0·05). The percentage reduction in lesion size was 29·30% for LeIF and 51·98% for LeIF + IL-12 than PBS at 12th week post-infection. Spleen parasite burden decreased in all immunized groups in comparison with control groups (P < 0·05). The results indicated that LeIF gene induced partial immunity against L. major infection in BALB/c mice. However, LeIF plus IL-12 group showed more potent immunity with smaller lesions than other groups.

摘要

先前的研究表明,利什曼原虫延伸起始因子(LeIF)抗原可引起对利什曼病的部分免疫力。该抗原通过白细胞介素-12(IL-12)、干扰素-γ(IFN-γ)和肿瘤坏死因子-α等炎性细胞因子的过表达产生I型免疫。因此,我们评估了LeIF基因针对硕大利什曼原虫感染诱导的免疫反应。单独用LeIF基因或与IL-12一起免疫诱导了Th1反应,与对照组相比,脾细胞产生的IFN-γ水平更高,IL-4水平更低(P<0.05),并且攻击后免疫组中IFN-γ/IL-4的比率比对照组高11.68至18.53倍。此外,体液免疫反应分析显示,免疫小鼠的IgG2a水平高于两个对照组(P<0.05)。另一方面,从攻击后第4周起,免疫动物的病变大小比对照组小(P<0.05)。在感染后第12周,与PBS相比,LeIF组的病变大小减少百分比为29.30%,LeIF+IL-12组为51.98%。与对照组相比,所有免疫组的脾脏寄生虫负荷均降低(P<0.05)。结果表明,LeIF基因在BALB/c小鼠中诱导了针对硕大利什曼原虫感染的部分免疫力。然而,LeIF加IL-12组显示出比其他组更强的免疫力,病变更小。

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