Author: 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.
Title: A host type I interferon response is induced by cytosolic sensing of the bacterial second messenger cyclic-di-GMP Document date: 2009_8_31
ID: 3b8b8p61_12
Snippet: It was previously reported that HEK293 cells stably transfected with various TLRs failed to respond to c-di-GMP (Karaolis et al., 2007a) , but the reason for this failure was unclear. For example, HEK293 cells might lack an essential accessory protein. To rule out a role for TLRs in sensing of c-di-GMP, we tested responses in Myd88 / Trif / double-knockout macrophages, which are deficient in all TLR signaling (Yamamoto et al., 2003) ......
Document: It was previously reported that HEK293 cells stably transfected with various TLRs failed to respond to c-di-GMP (Karaolis et al., 2007a) , but the reason for this failure was unclear. For example, HEK293 cells might lack an essential accessory protein. To rule out a role for TLRs in sensing of c-di-GMP, we tested responses in Myd88 / Trif / double-knockout macrophages, which are deficient in all TLR signaling (Yamamoto et al., 2003) . Both wild-type and Myd88 / Trif / macrophages showed a robust induction of IFN-î¢ after c-di-GMP stimulation (Fig. 2 A) . As expected, the Myd88 / Trif / macrophages did not respond to LPS (Fig. 2 A) . These results indicated that TLR signaling is not required for responsiveness to c-di-GMP, and are consistent with c-di-GMP signaling via a cytosolic surveillance pathway.
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