Infection-Induced Host Translational Blockage Inhibits Immune Responses and Epithelial Renewal in the Drosophila Gut
Infection-Induced Host Translational Blockage Inhibits Immune Responses and Epithelial Renewal in the Drosophila Gut
复制标题
DOI：
10.1016/j.chom.2012.06.001
复制
发表时间：
2012-07-19
影响因子：
30.3
通讯作者：
Lemaitre, Bruno
中科院分区：
文献类型：
--
作者：
Chakrabarti, Sveta;Liehl, Peter;Lemaitre, Bruno
通常，免疫反应控制病原体，而修复和应激途径则限制发病机制造成的损害。损伤对发病机制结果的相对贡献以及免疫和修复途径之间的机制联系知之甚少。在这里，我们分析了昆虫病原细菌嗜昆虫假单胞菌如何对果蝇肠道造成不可逆的损伤。我们发现，摄入昆虫假单胞菌会引起整体翻译阻断，从而损害果蝇肠道的免疫和修复程序。嗜虫假单胞菌诱导的翻译抑制依赖于细菌孔形成毒素和宿主响应感染而产生的活性氧。翻译停滞是通过 GCN2 激酶的激活和宿主损伤导致的 TOR 通路抑制来介导的。总之，我们的研究绘制了一个发病机制模型，其中细菌通过过度激活应激反应途径来抑制翻译，从而抑制免疫和再生上皮反应。
Typically, immune responses control the pathogen, while repair and stress pathways limit damage caused by pathogenesis. The relative contribution of damage to the outcome of pathogenesis and the mechanistic links between the immune and repair pathways are poorly understood. Here, we analyze how the entomopathogenic bacterium Pseudomonas entomophila induces irreversible damage to the Drosophila gut. We find that P. entomophila ingestion induces a global translational blockage that impairs both immune and repair programs in the fly gut. P. entomophila-induced translational inhibition is dependent on bacterial pore forming toxins and reactive oxygen species produced by the host in response to infection. Translational arrest is mediated through activation of the GCN2 kinase and inhibition of the TOR pathway as a consequence of host damage. Together, our study draws a model of pathogenesis in which bacterial inhibition of translation by excessive activation of stress responsive pathways inhibits both immune and regenerative epithelial responses.