TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages.
TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages.
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病原体的传感器，例如Toll样受体（TLR），检测微生物以激活转录程序，该转录程序协调对特定损伤的适应性反应。在这里，我们报告TLR 4和TLR 2特异性激活内质网（ER）-应激传感器激酶IRE 1 α及其下游靶点，转录因子XBP 1。之前描述的XBP 1 ER应激靶基因不受TLR信号传导诱导。相反，TLR激活的XBP 1是巨噬细胞中促炎细胞因子的最佳和持续产生所必需的。与这一发现一致，ER应激引起的IRE 1 α活化与TLR活化协同作用，产生细胞因子。此外，在感染TLR 2激活的人类病原体土拉弗朗西斯菌的动物中，XBP 1缺乏显著增加了细菌负荷。我们的发现揭示了哺乳动物宿主防御系统中XBP 1转录因子的一个未知的关键新功能。
Sensors of pathogens, such as Toll-like receptors (TLRs), detect microbes to activate transcriptional programs that orchestrate adaptive responses to specific insults. Here we report that TLR4 and TLR2 specifically activated the endoplasmic reticulum (ER)-stress sensor kinase IRE1α and its downstream target, the transcription factor XBP1. Previously described XBP1 ER stress target genes were not induced by TLR signaling. Instead, TLR-activated XBP1 was required for optimal and sustained production of proinflammatory cytokines in macrophages. Consistent with this finding, IRE1α activation by ER-stress synergized with TLR activation for cytokine production. Moreover, XBP1 deficiency markedly increased bacterial burden in animals infected with the TLR2-activating human pathogen Francisella tularensis. Our findings uncover an unsuspected critical new function for the XBP1 transcription factor in mammalian host defenses.
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影响因子：
3.1
作者：
Cole, Leah E.;Shirey, Kari Ann;Vogel, Stefanie N.
通讯作者：
Vogel, Stefanie N.
影响因子：
3.9
作者：
Grandvaux, Nathalie;Soucy-Faulkner, Anton;Fink, Karin
通讯作者：
Fink, Karin
影响因子：
3.7
作者：
Abplanalp, Allison L.;Morris, Ian R.;Berton, Michael T.
通讯作者：
Berton, Michael T.
DOI：
10.1196/annals.1409.014
发表时间：
2007-01-01
期刊：
FRANCISELLA TULARENSIS: BIOLOGY, PATHOGENICITY, EPIDEMIOLOGY, AND BIODEFENSE
影响因子：
--
作者：
Elkins, Karen L.;Cowley, Siobhan C.;Bosio, Catharine M.
通讯作者：
Bosio, Catharine M.
影响因子：
56.9
作者：
Lee, Ann-Hwee;Scapa, Erez F.;Glimcher, Laurie H.
通讯作者：
Glimcher, Laurie H.