A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP

McWhirter, Sarah M.; Barbalat, Roman; Monroe, Kathryn M.; Fontana, Mary F.; Hyodo, Mamoru; Joncker, Nathalie T.; Ishii, Ken J.; Akira, Shizuo; Colonna, Marco; Chen, Zhijian J.; Fitzgerald, Katherine A.; Hayakawa, Yoshihiro; Vance, Russell E.

Many cell types also appear to respond to the cytosolic presence of DNA Stetson and Medzhitov, 2006a) . The cytosolic response to DNA does not require MAVS, but does require TBK1 and IRF3 in most cell types Stetson and Medzhitov, 2006a; Sun et al., 2006) . Recently, a putative cytosolic sensor of DNA was identified, and was named DNA-dependent activator of IFN regulatory factors (DAI; previously known as DLM-1 or ZBP1; Takaoka et al., 2007) . Knockdown experiments indicated that DAI was involved in sensing cytosolic DNA in the L929 fibroblast-like and RAW macrophage-like cell lines (Takaoka et al., 2007; Wang et al., 2008) . DAI was expressed in other cell types, such as mouse embryonic fibroblasts (MEFs), but was dispensable for the response to cytosolic DNA in these cell types, suggesting that additional uncharacterized nucleic acid sensor proteins also exist . Indeed, cells from DAI knockouts appear to respond normally to cytosolic DNA (Ishii et al., 2008) , possibly because of redundancy with other cytosolic DNA sensors.