000198815 001__ 198815
000198815 005__ 20190316235916.0
000198815 0247_ $$2doi$$a10.1038/nature12640
000198815 022__ $$a1476-4687
000198815 037__ $$aARTICLE
000198815 245__ $$aCell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP
000198815 260__ $$c2013
000198815 269__ $$a2013
000198815 336__ $$aJournal Articles
000198815 500__ $$aLetter
000198815 520__ $$aThe innate immune defence of multicellular organisms against microbial pathogens requires cellular collaboration. Information exchange allowing immune cells to collaborate is generally attributed to soluble protein factors secreted by pathogen-sensing cells. Cytokines, such as type I interferons (IFNs), serve to alert non-infected cells to the possibility of pathogen challenge. Moreover, in conjunction with chemokines they can instruct specialized immune cells to contain and eradicate microbial infection. Several receptors and signalling pathways exist that couple pathogen sensing to the induction of cytokines, whereas cytosolic recognition of nucleic acids seems to be exquisitely important for the activation of type I IFNs, master regulators of antiviral immunity. Cytosolic DNA is sensed by the receptor cyclic GMP-AMP (cGAMP) synthase (cGAS), which catalyses the synthesis of the second messenger cGAMP(2'-5'). This molecule in turn activates the endoplasmic reticulum (ER)-resident receptor STING, thereby inducing an antiviral state and the secretion of type I IFNs. Here we find in murine and human cells that cGAS-synthesized cGAMP(2'-5') is transferred from producing cells to neighbouring cells through gap junctions, where it promotes STING activation and thus antiviral immunity independently of type I IFN signalling. In line with the limited cargo specificity of connexins, the proteins that assemble gap junction channels, most connexins tested were able to confer this bystander immunity, thus indicating a broad physiological relevance of this local immune collaboration. Collectively, these observations identify cGAS-triggered cGAMP(2'-5') transfer as a novel host strategy that serves to rapidly convey antiviral immunity in a transcription-independent, horizontal manner.
000198815 6531_ $$aCell Communication
000198815 700__ $$0248136$$g246669$$aAblasser, Andrea
000198815 700__ $$aSchmid-Burgk, Jonathan L.
000198815 700__ $$aHemmerling, Inga
000198815 700__ $$aHorvath, Gabor L.
000198815 700__ $$aSchmidt, Tobias
000198815 700__ $$aLatz, Eicke
000198815 700__ $$aHornung, Veit
000198815 773__ $$j503$$tNature$$k7477$$q530-4
000198815 8564_ $$uhttps://infoscience.epfl.ch/record/198815/files/nature12640.pdf$$zPublisher's version$$s3461482$$yPublisher's version
000198815 909C0 $$xU12938$$0252505$$pUPABLASSER
000198815 909CO $$qGLOBAL_SET$$pSV$$ooai:infoscience.tind.io:198815$$particle
000198815 917Z8 $$x182396
000198815 937__ $$aEPFL-ARTICLE-198815
000198815 973__ $$rREVIEWED$$sPUBLISHED$$aOTHER
000198815 980__ $$aARTICLE