Induction of TNF-alfa and CXCL-2 mRNAs in different organs of mice infected with pathogenic Leptospira
Induction of TNF-alfa and CXCL-2 mRNAs in different organs of mice infected with pathogenic Leptospira
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DOI：
10.1016/j.micpath.2012.01.002
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发表时间：
2012-04-01
影响因子：
3.8
通讯作者：
Martins, Elizabeth A. L.
中科院分区：
文献类型：
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作者：
da Silva, Josefa B.;Carvalho, Eneas;Martins, Elizabeth A. L.
先天免疫反应在预防钩端螺旋体病中的作用还知之甚少。我们检测了趋化因子CXCL2/MIP-2和细胞因子TNF-α的表达。在实验耐药和易感小鼠模型中，使用问号钩端螺旋体的强毒株，C3H/HeJ，C3H/HePas和BALB/c。用107细胞腹腔感染动物，观察疾病的发展过程。观察到C3H/HeJ小鼠死亡，而C3H/HePas小鼠出现黄疸，BALB/c小鼠无症状。通过聚合酶链式反应证实动物器官中存在钩端螺旋体DNA，证实了这种感染。H&E染色后进行组织切片分析。采用定量聚合酶链式反应技术检测小鼠肺、肾、肝组织中趋化因子CXCL2/MIP-2和细胞因子TNF-α的相对表达。用ELISA法测定动物组织提取液和血清中这些蛋白的浓度。从感染第一天起，CXCL2/MIP-2的转录本和蛋白表达水平逐渐升高。BALB/c小鼠感染后第3天肾、肝、肺组织中表达最强。C3H/HeJ组CXCL2/MIP-2表达延迟，第5天肺、肾组织蛋白表达最高。感染后，三个品系小鼠的肾脏和肝脏中的肿瘤坏死因子-α的转录本均升高。C3H/HeJ的肿瘤坏死因子-α蛋白表达也延迟，在肾脏和肺中均可检测到。结果表明，钩端螺旋体感染可刺激耐药小鼠早期表达CXCL2/MIP-2和肿瘤坏死因子-α。组织学分析表明，这些分子的表达可能与不同免疫细胞的涌入有关，并在自然获得性保护性免疫中发挥作用。(C)2012爱思唯尔有限公司。保留所有权利。
The role of innate immune response in protection against leptospirosis is poorly understood. We examined the expression of the chemokine CXCL2/MIP-2 and the cytokine TNF-alpha. in experimental resistant and susceptible mice models, C3H/HeJ, C3H/HePas and BALB/c strains, using a virulent strain of Leptospira interrogans serovar Copenhageni. Animals were infected intraperitoneally with 107 cells and the development of the disease was followed. Mortality of C3H/HeJ mice was observed whereas C3H/HePas presented jaundice and BALB/c mice remained asymptomatic. The infection was confirmed by the presence of leptospiral DNA in the organs of the animals, demonstrated by PCR. Sections of the organs were analyzed, after H&E stain. The relative expression of mRNA of chemokine CXCL2/MIP-2 and cytokine TNF-alpha was measured in lung, kidney and liver of the mice by qPCR. The concentrations of these proteins were measured in extracts of tissues and in serum of the animals, by ELISA. Increasing levels of transcripts and protein CXCL2/MIP-2 were detected since the first day of infection. The highest expression was observed at third day of infection in kidney, liver and lung of BALB/c mice. In C3H/HeJ the expression of CXCL2/MIP-2 was delayed, showing highest protein concentration in lung and kidney at the 5th day. Increasing in TNF-alpha transcripts were detected after infection, in kidney and liver of animals from the three mice strains. The expression of TNF-alpha protein in C3H/HeJ was also delayed, being detected in kidney and lung. Our data demonstrated that Leptospira infection stimulates early expression of CXCL2/MIP-2 and TNF-alpha in the resistant strain of mice. Histological analysis suggests that the expression of those molecules may be related to the influx of distinct immune cells and plays a role in the naturally acquired protective immunity. (C) 2012 Elsevier Ltd. All rights reserved.