通过细胞内识别细胞外细菌病原体的DNA，引发不依赖Toll样受体的I型干扰素诱导反应。
TLR-independent type I interferon induction in response to an extracellular bacterial pathogen via intracellular recognition of its DNA.
作者信息
Charrel-Dennis Marie, Latz Eicke, Halmen Kristen A, Trieu-Cuot Patrick, Fitzgerald Katherine A, Kasper Dennis L, Golenbock Douglas T
机构信息
Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
出版信息
Cell Host Microbe. 2008 Dec 11;4(6):543-54. doi: 10.1016/j.chom.2008.11.002.
Abstract
Type I interferon (IFN) is an important host defense cytokine against intracellular pathogens, mainly viruses. In assessing IFN production in response to group B streptococcus (GBS), we find that IFN-beta was produced by macrophages upon stimulation with both heat-killed and live GBS. Exposure of macrophages to heat-killed GBS activated a Toll-like receptor (TLR)-dependent pathway, whereas live GBS activated a TLR/NOD/RIG-like receptor (RLR)-independent pathway. This latter pathway required bacterial phagocytosis, proteolytic bacterial degradation, and phagolysosomal membrane destruction by GBS pore-forming toxins, leading to the release of bacterial DNA into the cytosol. GBS DNA in the cytosol induced IFN-beta production via a pathway dependent on the activation of the serine-threonine kinase TBK1 and phosphorylation of the transcription factor IRF3. Thus, activation of IFN-alpha/-beta production during infection with GBS, commonly considered an extracellular pathogen, appears to result from the interaction of GBS DNA with a putative intracellular DNA sensor or receptor.
摘要
I型干扰素（IFN）是一种针对细胞内病原体（主要是病毒）的重要宿主防御细胞因子。在评估对B族链球菌（GBS）作出反应时的IFN产生情况时，我们发现巨噬细胞在用热灭活的和活的GBS刺激后都会产生IFN-β。巨噬细胞暴露于热灭活的GBS会激活一条依赖Toll样受体（TLR）的途径，而活的GBS则激活一条不依赖TLR/核苷酸结合寡聚化结构域（NOD）/视黄酸诱导基因样受体（RLR）的途径。后一条途径需要细菌吞噬作用、细菌蛋白水解降解以及GBS成孔毒素对吞噬溶酶体膜的破坏，从而导致细菌DNA释放到细胞质中。细胞质中的GBS DNA通过一条依赖丝氨酸-苏氨酸激酶TBK1激活和转录因子IRF3磷酸化的途径诱导IFN-β产生。因此，在感染通常被认为是细胞外病原体的GBS期间，IFN-α/-β产生的激活似乎是GBS DNA与一种假定的细胞内DNA传感器或受体相互作用的结果。
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