IFI16 is an innate immune sensor for intracellular DNA.
IFI16 is an innate immune sensor for intracellular DNA.
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细胞内微生物DNA的检测对于适当的先天免疫反应至关重要，然而目前关于这种DNA如何被感知的知识有限。在这里，我们发现IFI16，一个PYHIN蛋白，作为细胞内DNA传感器介导干扰素-β (IFNβ)诱导。IFI16直接与ifn β诱导的病毒DNA基序相关。STING是IFNβ对DNA反应的关键介质，在DNA刺激后被招募到IFI16中。通过RNA干扰降低IFI16或其小鼠同源基因p204的表达，可抑制DNA和单纯疱疹病毒(HSV)-1诱导的基因诱导以及IRF3和NFκB的激活。IFI16/p204是第一个被证明参与IFNβ诱导的PYHIN蛋白，因此与AIM2（一种感知DNA的caspase 1激活的PYHIN蛋白）一起，是一个新的先天DNA传感器家族的一部分，我们称之为AIM2样受体（ALRs）。
The detection of intracellular microbial DNA is critical to an appropriate innate immune response, however current knowledge on how such DNA is sensed is limited. Here we identify IFI16, a PYHIN protein, as an intracellular DNA sensor mediating interferon-β (IFNβ)-induction. IFI16 directly associated with IFNβ-inducing viral DNA motifs. STING, a critical mediator of IFNβ responses to DNA, was recruited to IFI16 after DNA stimulation. Reduction of expression of IFI16, or its murine ortholog p204, by RNA interference inhibited DNA- and herpes simplex virus (HSV)-1-induced gene induction and IRF3 and NFκB activation. IFI16/p204 is the first PYHIN protein shown to be involved in IFNβ induction, and thus together with AIM2, a PYHIN protein that senses DNA for caspase 1 activation, is part of a new family of innate DNA sensors which we term AIM2-like receptors (ALRs).