Host translational inhibition by Pseudomonas aeruginosa Exotoxin A Triggers an immune response in Caenorhabditis elegans.
Host translational inhibition by Pseudomonas aeruginosa Exotoxin A Triggers an immune response in Caenorhabditis elegans.
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DOI：
10.1016/j.chom.2012.02.007
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发表时间：
2012-04-19
影响因子：
30.3
通讯作者：
Ausubel FM
中科院分区：
文献类型：
--
作者：
McEwan DL;Kirienko NV;Ausubel FM
肠上皮细胞暴露于无害和致病微生物，需要区分以产生有效的免疫应答。为了了解病原体识别的机制，我们研究了铜绿假单胞菌如何触发秀丽隐杆线虫的肠道先天免疫，这是一个独立于Toll样模式识别受体的过程。我们发现，铜绿假单胞菌翻译抑制剂外毒素A（ToxA），核糖基化延伸因子2（EF 2），上调一个显着的基因亚组通常由铜绿假单胞菌诱导。此外，涉及ATF-7和ZIP-2转录因子的免疫途径，保护C。来自铜绿假单胞菌（P. aeruginosa）的秀丽隐杆线虫是防止ToxA介导的致死性所必需的。ToxA应答基因不受酶失活的ToxA蛋白诱导，但可以通过破坏宿主蛋白翻译独立于ToxA上调。因此，C.线虫具有通过其对蛋白质翻译的影响而不是通过ToxA或核糖基化EF 2的直接识别来识别ToxA的监视机制。
Intestinal epithelial cells are exposed to both innocuous and pathogenic microbes, which need to be distinguished to mount an effective immune response. To understand the mechanisms underlying pathogen recognition, we investigated how Pseudomonas aeruginosa triggers intestinal innate immunity in Caenorhabditis elegans, a process independent of Toll-like pattern recognition receptors. We show that the P. aeruginosa translational inhibitor Exotoxin A (ToxA), which ribosylates elongation factor 2 (EF2), upregulates a significant subset of genes normally induced by P. aeruginosa. Moreover, immune pathways involving the ATF-7 and ZIP-2 transcription factors, which protect C. elegans from P. aeruginosa, are required for preventing ToxA-mediated lethality. ToxA-responsive genes are not induced by enzymatically inactive ToxA protein but can be upregulated independently of ToxA by disruption of host protein translation. Thus, C. elegans has a surveillance mechanism to recognize ToxA through its effect on protein translation rather than by direct recognition of either ToxA or ribosylated EF2.
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影响因子：
56.9
作者：
Garsin, DA;Villanueva, JM;Ausubel, FM
通讯作者：
Ausubel, FM
影响因子：
7.8
作者：
Hansen, Malene;Taubert, Stefan;Kenyon, Cynthia
通讯作者：
Kenyon, Cynthia
影响因子：
4.9
作者：
EUSTICE, DC;WILHELM, JM
通讯作者：
WILHELM, JM
DOI：
10.1073/pnas.0914643107
发表时间：
2010-02-02
影响因子：
11.1
作者：
Estes, Kathleen A.;Dunbar, Tiffany L.;Troemel, Emily R.
通讯作者：
Troemel, Emily R.
影响因子：
56.9
作者：
Kim, DH;Feinbaum, R;Ausubel, FM
通讯作者：
Ausubel, FM