Department of Infection Genetics, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Microbes Infect. 2010 Apr;12(4):309-18. doi: 10.1016/j.micinf.2010.01.008. Epub 2010 Jan 28.
Inbred mouse strains exhibit differences in susceptibility to influenza A infections. However, the molecular mechanisms underlying these differences are unknown. Therefore, we infected a highly susceptible mouse strain (DBA/2J) and a resistant strain (C57BL/6J) with influenza A H1N1 (PR8) and performed genome-wide expression analysis. We found genes expressed in lung epithelium that were specifically down-regulated in DBA/2J mice, whereas a cluster of genes on chromosome 3 was only down-regulated in C57BL/6J. In both mouse strains, chemokines, cytokines and interferon-response genes were up-regulated, indicating that the main innate immune defense pathways were activated. However, many immune response genes were up-regulated in DBA/2J much stronger than in C57BL/6J, and several immune response genes were exclusively regulated in DBA/2J. Thus, susceptible DBA/2J mice showed a hyper-inflammatory response. This response is similar to infections with highly pathogenic influenza virus and may serve as a paradigm for a hyper-inflammatory host response to influenza A virus.
近交系小鼠对流感 A 感染的易感性存在差异。然而，这些差异的分子机制尚不清楚。因此，我们用流感 A H1N1（PR8）感染了一种高度易感的小鼠品系（DBA/2J）和一种抗性品系（C57BL/6J），并进行了全基因组表达分析。我们发现了在肺上皮细胞中表达的基因，这些基因在 DBA/2J 小鼠中特异性地下调，而 3 号染色体上的一组基因仅在 C57BL/6J 中下调。在这两种小鼠品系中，趋化因子、细胞因子和干扰素反应基因都上调，表明主要的先天免疫防御途径被激活。然而，许多免疫反应基因在 DBA/2J 中的上调幅度比在 C57BL/6J 中要强得多，而且有几个免疫反应基因仅在 DBA/2J 中受到调节。因此，易感的 DBA/2J 小鼠表现出强烈的炎症反应。这种反应类似于感染高致病性流感病毒，可能是流感 A 病毒引起的过度炎症宿主反应的范例。
