Humphreys Neil E, Grencis Richard K
Faculty of Life Sciences, The University of Manchester, Manchester, UK.
Eur J Immunol. 2009 Apr;39(4):1036-45. doi: 10.1002/eji.200838938.
IL-1 null mice are unable to expel the intestinal nematode Trichuris muris; whereas WT littermates exhibit sterile immunity. Intriguingly the essential signalling components IL-1R1 and IL-1R accessory protein (AcP) are dispensable for expulsion of this parasite. IL-1 is thus critical for CD4(+) Th2-mediated immunity to T. muris; however, this action is independent of the established IL-1 signalling receptor. We also present data demonstrating that both IL-1alpha and IL-1beta induce measurable effects on T. muris primed cells isolated from IL-1R1 or IL-1R AcP null mice. MLN cells from these mice restimulated with parasite antigen proliferated at a greater rate and produced more cytokines in response to exogenous IL-1. This ability to respond to IL-1 was restricted to these parasite-primed cells and importantly was not evident in cells from naïve gene null mice. These in vitro data are consistent with the observed ability of mice with compromised IL-1 signalling to expel the parasite, bolstering the premise that an alternative IL-1 signalling mechanism is accessible in the context of an intestinal helminth-driven Th2 immune response.
白细胞介素-1基因敲除小鼠无法驱除肠道线虫毛首鞭形线虫；而野生型同窝小鼠则表现出无菌免疫。有趣的是，基本信号传导成分白细胞介素-1受体1（IL-1R1）和白细胞介素-1受体辅助蛋白（AcP）对于驱除这种寄生虫并非必需。因此，白细胞介素-1对于CD4(+) Th2介导的针对毛首鞭形线虫的免疫至关重要；然而，这一作用独立于既定的白细胞介素-1信号受体。我们还提供了数据，证明白细胞介素-1α和白细胞介素-1β对从白细胞介素-1R1或白细胞介素-1R AcP基因敲除小鼠分离的经毛首鞭形线虫致敏的细胞均有可测量的影响。用寄生虫抗原再次刺激这些小鼠的肠系膜淋巴结（MLN）细胞，其增殖速度更快，对外源性白细胞介素-1的反应产生更多细胞因子。这种对白细胞介素-1的反应能力仅限于这些经寄生虫致敏的细胞，重要的是，在未接触过抗原的基因敲除小鼠的细胞中并不明显。这些体外数据与观察到的白细胞介素-1信号传导受损的小鼠驱除寄生虫的能力一致，支持了在肠道蠕虫驱动的Th2免疫反应背景下可利用替代白细胞介素-1信号传导机制这一前提。
