Department of Immunology, College of Basic Medical Sciences, China Medical University, No. 92 Bei Er Ma Lu, Shenyang, Liaoning, 110001, China,
Immunogenetics. 2014 Apr;66(4):231-42. doi: 10.1007/s00251-014-0761-x. Epub 2014 Feb 25.
Inbred stains of mice display differential susceptibility to infection with the common foodborne pathogen Listeria monocytogenes (Lm). Previously, Listr1 and Listr2, two genetic loci that control differential sensitivity to Lm infection between BALB/cByJ and C57BL/6ByJ mice, were identified. To analyze the role of Listr1 in innate immune responses, we employed congenic mice (C.B6By-Listr1/Rag2 (-/-) ) bearing the C57BL/6ByJ-derived Listr1 locus on a BALB/c-Rag2 (-/-) background. Consistent with the results of a previous genetic analysis, the congenic mice showed increased susceptibility to Lm infection. The bacterial burden in the liver between the congenic and control lines was significantly different (P < 0.05) from 24 h postinfection with Lm. Analysis of genes within the Listr1 locus identified a frameshift mutation in the Cxcl11 gene of the C57BL/6 strain that prevents production of the mature chemokine CXCL11. No differences in inflammatory cell infiltration or cells expressing CXCR3 and CXCR7 which are the receptors of CXCL11 occurred because of CXCL11 deficiency in the congenic mice spleens. However, these mice lacked a distinct population of CD14(+) positive resident mononuclear cells that express intermediate levels of CXCR3 and CXCR7 in the liver. There were fewer microabscesses in the liver of CXCL11-deficient mice during the early stage of infection, which is consistent with their decreased ability to resist Lm. Our results, when taken together, show that the Listr1 locus plays an important role in early control of Lm infection in the mouse liver and that Cxcl11 is a candidate gene for disease severity within this locus.
近交品系的小鼠对常见食源性病原体李斯特菌（Lm）的感染易感性存在差异。此前，已经确定了两个遗传位点 Listr1 和 Listr2，它们控制 BALB/cByJ 和 C57BL/6ByJ 小鼠对 Lm 感染的敏感性差异。为了分析 Listr1 在先天免疫反应中的作用，我们使用了带有 C57BL/6ByJ 衍生 Listr1 基因座的同源重组小鼠（C.B6By-Listr1/Rag2 (-/-) ），该基因座位于 BALB/c-Rag2 (-/-) 背景下。与之前的遗传分析结果一致，同源重组小鼠对 Lm 感染的敏感性增加。从 Lm 感染后 24 小时开始，肝脏中的细菌负荷在同源重组和对照品系之间存在显著差异（P < 0.05）。在 Listr1 基因座内的基因分析中，发现 C57BL/6 品系的 Cxcl11 基因发生了移码突变，阻止了成熟趋化因子 CXCL11 的产生。由于同源重组小鼠脾脏中 CXCL11 的缺失，没有发生趋化因子 CXCL11 缺乏导致的炎性细胞浸润或表达 CXCR3 和 CXCR7 的细胞增加。然而，这些小鼠肝脏中缺乏表达中间水平 CXCR3 和 CXCR7 的 CD14(+)阳性常驻单核细胞的特定群体。在感染的早期阶段，CXCL11 缺陷小鼠肝脏中的微脓肿较少，这与其抵抗 Lm 的能力下降一致。我们的研究结果表明，Listr1 基因座在小鼠肝脏中对 Lm 感染的早期控制中起着重要作用，Cxcl11 是该基因座内疾病严重程度的候选基因。
