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在 BALB/c 小鼠中,基因型不同的利什曼原虫主要菌株表现出不同的临床和免疫模式。

Genotypically distinct strains of Leishmania major display diverse clinical and immunological patterns in BALB/c mice.

机构信息

Department of Immunology, Pasteur Institute of Iran, Pasteur Avenue 69, Tehran, Iran.

出版信息

Infect Genet Evol. 2010 Oct;10(7):969-75. doi: 10.1016/j.meegid.2010.06.006. Epub 2010 Jun 22.

DOI:10.1016/j.meegid.2010.06.006
PMID:20601170
Abstract

Infection with Leishmania major species is endemic in many provinces of Iran. Isolates from four endemic areas located in north (Damghan), center (Kashan), west (Dehloran), and south (Shiraz) of country which showed major distinctive polymorphism by RAPD-PCR method were evaluated. Isolates were inoculated to different groups of BALB/c mice and their clinical and immunological status was compared. Lesion size, parasite burden and T cell phenotype in lymph node (LN), and cytokine secretion in the culture of LN mononuclear cells were determined. The results showed the lowest and highest lesion sizes in mice infected by Shiraz strain (3.02+/-0.52 mm) and Kashan strain (5.20+/-0.45), respectively, 8 weeks after inoculation. No significant difference was observed between other strains. The parasite burden was significantly lower in lymph node of mice infected with strain of Damghan (1.51 x 10(7)) than Kashan (3.60 x 10(9)) and Shiraz (7.08 x 10(9)) strains, 8 weeks post-infection. However, Dehloran strain showed intermediate load of viable parasites (1.51 x 10(9)) in LN, 8 weeks post-infection. High ratios of IFN-gamma/IL-4 were shown in mice inoculated by strain of Dehloran (3.17) and Damghan (2.66), but not in mice infected by other strains, 8 weeks post-infection. The highest and lowest ratios of CD4(+)/CD8(+) T cells were found in LN cells of mice infected with Kashan (1.82) and Dehloran (1.00) strains, respectively. Results indicate that the lowest and intermediate loads of parasites induced by Damghan and Dehloran strains along with higher ratio of IFN-gamma/IL-4 produced by both strains in LN of inoculated mice suggest that these strains have the capacity to shift the immune responses to a predominant Th1 response after 8 weeks infection in BALB/c mice and might be the ideal strains for vaccine studies and development of candidate vaccine against leishmaniasis.

摘要

利什曼原虫种感染在伊朗许多省份流行。通过 RAPD-PCR 方法,对来自该国北部(达姆甘)、中部(卡尚)、西部(德莱赫兰)和南部(设拉子)四个流行地区的分离株进行了评估,这些分离株表现出主要的显著多态性。将分离株接种到不同组的 BALB/c 小鼠中,并比较它们的临床和免疫状态。测定了淋巴结(LN)中的病变大小、寄生虫负荷和 T 细胞表型,以及 LN 单核细胞培养物中的细胞因子分泌。结果显示,接种后 8 周,感染设拉子株的小鼠(3.02+/-0.52mm)和感染卡尚株的小鼠(5.20+/-0.45mm)的病变最小和最大。其他菌株之间没有显著差异。感染达姆甘株(1.51x10(7))的小鼠淋巴结中的寄生虫负荷明显低于感染卡尚株(3.60x10(9))和感染设拉子株(7.08x10(9))的小鼠,感染后 8 周。然而,感染德莱赫兰株的小鼠 LN 中的活寄生虫负荷为中等水平(1.51x10(9)),感染后 8 周。感染德莱赫兰株(3.17)和达姆甘株(2.66)的小鼠 IFN-γ/IL-4 的比值较高,但感染其他菌株的小鼠 IFN-γ/IL-4 的比值不高,感染后 8 周。感染卡尚株(1.82)和感染德莱赫兰株(1.00)的小鼠 LN 中 CD4+/CD8+T 细胞的比值最高和最低。结果表明,感染达姆甘株和德莱赫兰株后,寄生虫的负荷最低和中等,以及这两个菌株在接种小鼠的 LN 中产生的 IFN-γ/IL-4 的比值较高,这表明这些菌株在 BALB/c 小鼠感染 8 周后具有将免疫反应转向以 Th1 反应为主的能力,可能是利什曼病疫苗研究和候选疫苗开发的理想菌株。

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