TMEM173 is a recently identified adaptor found to be a critical component of the cellular innate immune response to pathogenic cytoplasmic DNA. It is ubiquitously expressed, resides in the ER, and has five transmembrane regions. Detection of cytoplasmic DNA by nucleic acid sensors such as DDX41 or IFI16 leads to their association with STING. This causes STING, in a complex with TBK1, to traffic through the Golgi to perinuclear endosomes where TBK1 phosphorylates and activates IRFs and NF-kappaB, ultimately leading to induction of type I interferon and other genes important for the immune response. In addition, RIG-I, the cytoplasmic receptor for 5" triphosphorylated viral RNA, was shown to associate with and require STING for induction of type I interferon. Finally, STING was recently demonstrated to be a direct sensor of cyclic dinucleotides produced by bacteria.
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