Leishmania tarentolae expressing CXCL-10 as an efficient immunotherapy approach against Leishmania major-infected BALB/c mice

被引:19
|
作者
Montakhab-Yeganeh, H. [1 ]
Abdossamadi, Z. [2 ]
Zahedifard, F. [2 ]
Taslimi, Y. [2 ]
Badirzadeh, A. [2 ]
Saljoughian, N. [2 ]
Taheri, T. [2 ]
Taghikhani, M. [1 ]
Rafati, S. [2 ]
机构
[1] Tarbiat Modares Univ, Dept Clin Biochem, Fac Med Sci, Tehran, Iran
[2] Pasteur Inst Iran, Dept Immunotherapy & Leishmania Vaccine Res, Tehran, Iran
关键词
CXCL-10; gene therapy; immunotherapy; L; major-infected BALB; c mice; tarentolae; live therapy; VISCERAL LEISHMANIASIS; IMMUNE-RESPONSE; NITRIC-OXIDE; DELIVERY-SYSTEM; IP-10; PROTECTION; ARGINASE; CHEMOKINE; GROWTH; VACCINATION;
D O I
10.1111/pim.12461
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 3weeks post-treatment by evaluating the parameters of parasite burden (PB), arginase activity, NO and various cytokines such as IFN-, 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.
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页数:11
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