Danne, CamilleRyzhakov, GrigoryMartinez-Lopez, MariaIlott, Nicholas EdwardFranchini, FannyCuskin, FionaLowe, Elisabeth CBullers, Samuel JArthur, J Simon CPowrie, Fiona2019-03-112019-03-112017-12-13Cell Host Microbe. 2017; 22(6):733-7451931-3128http://hdl.handle.net/20.500.12105/7310Interactions between the host and its microbiota are of mutual benefit and promote health. Complex molecular pathways underlie this dialog, but the identity of microbe-derived molecules that mediate the mutualistic state remains elusive. Helicobacter hepaticus is a member of the mouse intestinal microbiota that is tolerated by the host. In the absence of an intact IL-10 signaling, H. hepaticus induces an IL-23-driven inflammatory response in the intestine. Here we investigate the interactions between H. hepaticus and host immune cells that may promote mutualism, and the microbe-derived molecule(s) involved. Our results show that H. hepaticus triggers early IL-10 induction in intestinal macrophages and produces a large soluble polysaccharide that activates a specific MSK/CREB-dependent anti-inflammatory and repair gene signature via the receptor TLR2. These data identify a host-bacterial interaction that promotes mutualistic mechanisms at the intestinal interface. Further understanding of this pathway may provide novel prevention and treatment strategies for inflammatory bowel disease.engVoRhttp://creativecommons.org/licenses/by/4.0/CREBHelicobacter hepaticusMSK1/2TLR2Anti-inflammatory gene signatureHost-microbe interactionsInflammatory bowel diseaseMacrophageMutualismPolysaccharideAnimalsHelicobacter hepaticusImmunosuppressive AgentsInterleukin-10Interleukin-23MacrophagesMicePolysaccharides, BacterialToll-Like Receptor 2SymbiosisAtribución 4.0 Internacional29241040226733-745.e510.1016/j.chom.2017.11.0021934-6069Cell host & microbeopen access