Genetic and physiological activation of osmosensitive gene expression mimics transcriptional signatures of pathogen infection in C. elegans.
Genetic and physiological activation of osmosensitive gene expression mimics transcriptional signatures of pathogen infection in C. elegans.
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DOI：
10.1371/journal.pone.0009010
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发表时间：
2010-02-02
期刊：
影响因子：
3.7
通讯作者：
Lamitina T
中科院分区：
文献类型：
--
作者：
Rohlfing AK;Miteva Y;Hannenhalli S;Lamitina T
土壤线虫秀丽隐杆线虫是对环境胁迫响应机制进行比较分子分析的强大系统。细菌和真菌病原体感染线虫会导致暴露于病原体的皮下组织和肠道组织中特征明确的先天免疫转录程序被激活。然而，驱动这种转录反应的病理生理事件尚不清楚。在这里，我们表明感染激活的转录反应在很大程度上是通过渗透应激反应的生理或遗传激活来概括的。对暴露于非致死性高渗状态的野生型蠕虫进行微阵列分析，发现了一组也受到感染调节的基因。等渗条件下五种不同的抗渗透胁迫（osr）突变体的表达谱重申了野生型对渗透胁迫的转录反应，并且还显示出与等渗条件下感染诱导的基因表达的显着相似性。计算、转基因和功能方法表明，先前与感染诱导的转录反应有关的两种 GATA 转录因子 elt-2 和 elt-3 对于渗透敏感基因表达的协调组织特异性激活和促进渗透应激条件下的生存也至关重要。总之，我们的数据表明感染和渗透适应具有以前未被认识到的转录相似性，这些相似性可能通过组织特异性 GATA 转录因子的调节来控制。
The soil-dwelling nematode C. elegans is a powerful system for comparative molecular analyses of environmental stress response mechanisms. Infection of worms with bacterial and fungal pathogens causes the activation of well-characterized innate immune transcriptional programs in pathogen-exposed hypodermal and intestinal tissues. However, the pathophysiological events that drive such transcriptional responses are not understood. Here, we show that infection-activated transcriptional responses are, in large part, recapitulated by either physiological or genetic activation of the osmotic stress response. Microarray profiling of wild type worms exposed to non-lethal hypertonicity identified a suite of genes that were also regulated by infection. Expression profiles of five different osmotic stress resistant (osr) mutants under isotonic conditions reiterated the wild type transcriptional response to osmotic stress and also showed substantial similarity to infection-induced gene expression under isotonic conditions. Computational, transgenic, and functional approaches revealed that two GATA transcription factors previously implicated in infection-induced transcriptional responses, elt-2 and elt-3, are also essential for coordinated tissue-specific activation of osmosensitive gene expression and promote survival under osmotically stressful conditions. Together, our data suggest infection and osmotic adaptation share previously unappreciated transcriptional similarities which might be controlled via regulation of tissue-specific GATA transcription factors.
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