Leishmania donovani: CD2 biased immune response skews the SAG mediated therapy for a predominant Th1 response in experimental infection
Leishmania donovani: CD2 biased immune response skews the SAG mediated therapy for a predominant Th1 response in experimental infection
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DOI：
10.1016/j.exppara.2012.04.007
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发表时间：
2012-07-01
影响因子：
2.1
通讯作者：
Das, Pradeep
中科院分区：
文献类型：
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作者：
Bimal, Sanjiva;Sinha, Sukrat;Das, Pradeep
我们已经评估了CD 2与常规锑（sb）治疗相结合对通过心内途径感染杜氏利什曼原虫药物敏感或耐药株的BALB/c小鼠的保护作用。小鼠用抗CD 2辅助SAG皮下注射治疗，每周两次，持续4周。在处理后第0、10、22和34天进行体重、脾脏大小、抗利什曼原虫抗体滴度、T细胞和抗利什曼原虫巨噬细胞功能的测量评估。与SAG单一疗法相比，联合疗法显示出提高了表达⑶ 25的T细胞的显著比例。尽管IFN-γ的水平在组合与单一疗法之间没有统计学差异（p = 0.298），但在Ld-S菌株以及Ld-R菌株中，CD 2治疗甚至单独比SAG治疗（p = 0.045）或CD 2辅助SAG治疗（p = 0.005）显著影响IFN-γ产生。还记录了CD 2辅助治疗对巨噬细胞抗利什曼功能的影响。如图所示，超氧化物生成在用CD 2进行SAG处理后的第10天很早就开始增强，在此期间SAG作用最小。有趣的是，即使在感染利什曼原虫耐药株的小鼠中，免疫化疗治疗后巨噬细胞的超氧化物生成能力也保持不变。与SAG治疗不同，用CD 2治疗SAG还导致一氧化氮和TNF-α的产生，导致最有效的L.感染巨噬细胞的Donovani。我们的研究结果表明，CD 2可以增强保护性Th 1应答，也可能有助于SAG诱导Macrophages产生杀利什曼原虫分子，从而控制黑热病等临床感染。抗药性是疾病控制的主要阻力，但用寄生虫的耐药菌株感染小鼠后获得的令人鼓舞的结果强烈暗示，这种药物即使在治疗黑热病的耐药病例中也是有效的。(C)2012 Elsevier Inc. All rights reserved.
We have evaluated the effect of combining CD2 with conventional antimonial (sb) therapy in protection in BALB/c mice infected with either drug sensitive or resistant strain of Leishmania donovani with 3 x 10(7) parasites via-intra-cardiac route. Mice were treated with anti CD2 adjunct SAG sub-cutaneously twice a week for 4 weeks. Assessment for measurement of weight, spleen size, anti-Leishmania antibody titer, T cell and anti-leishmanial macrophage function was carried out day 0, 10, 22 and 34 post treatments. The combination therapy was shown boosting significant proportion of T cells to express CD25 compared to SAG monotherapy. Although, the level of IFN-gamma was not statistically different between combination vs monotherapy (p = 0.298) but CD2 treatment even alone significantly influenced IFN-gamma production than either SAG treatment (p = 0.045) or with CD2 adjunct SAG treatment (p = 0.005) in Ld-S strain as well as in Ld-R strain. The influence of CD2 adjunct treatment was also documented in anti-leishmanial functions in macrophages. As shown, the super-oxide generation began enhancing very early on day 10 after SAG treatment with CD2 during which SAG action was at minimum. Interestingly, the super-oxide generation ability remained intact in macrophage after treatment with immuno-chemotherapy even in mice infected with Leishmania resistant strain. Unlike SAG treatment, treatment of SAG with CD2 also led to production of nitric oxide and TNF-alpha, resulting in resulting in most effective clearance of L. donovani from infected macrophages. Our results indicate that CD2, which can boost up a protective Th1 response, might also be beneficial to enable SAG to induce Macrophages to produce Leishmanicidal molecules and hence control the infection in clinical situation like Kala-azar. Drug resistance is the major impedance for disease control but the encouraging results obtained after infecting mice with resistant strain of the parasite strongly imply that this drug can be effective even in treating resistant cases of Kala-azar. (C) 2012 Elsevier Inc. All rights reserved.