Montakhab-Yeganeh H, Abdossamadi Z, Zahedifard F, Taslimi Y, Badirzadeh A, Saljoughian N, Taheri T, Taghikhani M, Rafati S
Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran.
Parasite Immunol. 2017 Oct;39(10). doi: 10.1111/pim.12461.
Recent findings have demonstrated the suitability of interferon-gamma-induced protein 10 (IP-10) or CXCL-10 as an immunotherapy tool in treatment of leishmaniasis. This chemokine can overcome Leishmania (L.) infection through inducing nitric oxide (NO) production for parasite elimination. This study was undertaken to investigate the therapeutic effects of recombinant Leishmania tarentolae expressing CXCL-10 and an expression vector encoding CXCL-10 (pcDNA-CXCL-10-EGFP) in a model of BALB/c mice susceptible to infection by Leishmania major. The outcome of intervention was examined at 3 weeks post-treatment by evaluating the parameters of parasite burden (PB), arginase activity, NO and various cytokines such as IFN-γ, IL-4, IL-6 and IL-10. The results have shown that despite the efficacy of CXCL-10 expression vector as gene therapy, the live therapy strategy using L. tarentolae expressing CXCL-10 was more effective in terms of decreasing PB. Nitric oxide production increased, especially in the live therapy approaches. Arginase activity also decreased in all regimens, which demonstrates the potency of the treatment. The overall cytokine production shifted in favour of Th1 responses in the treated mice. Altogether, recombinant L. tarentolae expressing CXCL-10 represents a promising therapeutic strategy to improve treatment of cutaneous leishmaniasis.
最近的研究结果表明,干扰素-γ诱导蛋白10(IP-10)或CXCL-10作为免疫治疗工具在治疗利什曼病方面具有适用性。这种趋化因子可以通过诱导产生一氧化氮(NO)来消除寄生虫,从而克服利什曼原虫感染。本研究旨在探讨表达CXCL-10的重组塔里亚布利什曼原虫和编码CXCL-10的表达载体(pcDNA-CXCL-10-EGFP)在易受硕大利什曼原虫感染的BALB/c小鼠模型中的治疗效果。在治疗后3周,通过评估寄生虫负荷(PB)、精氨酸酶活性、NO以及各种细胞因子如IFN-γ、IL-4、IL-6和IL-10等参数来检查干预结果。结果表明,尽管CXCL-10表达载体作为基因治疗有效,但使用表达CXCL-10的塔里亚布利什曼原虫的活菌治疗策略在降低PB方面更有效。一氧化氮的产生增加,特别是在活菌治疗方法中。所有治疗方案中的精氨酸酶活性也降低,这表明了治疗的有效性。在治疗的小鼠中,总体细胞因子产生向有利于Th1反应的方向转变。总之,表达CXCL-10的重组塔里亚布利什曼原虫是一种有前景的治疗策略,可改善皮肤利什曼病的治疗。