title: Stimulation of the intracellular bacterial sensor NOD2 programs dendritic cells to promote interleukin-17 production in human memory T cells.
abstract: How the development of antibacterial T helper 17 (Th17) cells is selectively promoted by antigen-presenting dendritic cells (DCs) is unclear. We showed that bacteria, but not viruses, primed human DCs to promote IL-17 production in memory Th cells through the nucleotide oligomerization domain 2 (NOD2)-ligand muramyldipeptide (MDP), a derivative of bacterial peptidoglycan. MDP enhanced obligate bacterial Toll-like receptor (TLR) agonist induction of IL-23 and IL-1, which promoted IL-17 expression in T cells. The role of NOD2 in this IL-23-IL-1-IL-17 axis could be confirmed in NOD2-deficient DCs, such as DCs from selected Crohn's disease patients. Thus, antibacterial Th17-mediated immunity in humans is orchestrated by DCs upon sensing bacterial NOD2-ligand MDP.
authors.affiliation: Department of Cell Biology and Histology, Academic Medical Centre of the University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Astrid J
authors.initials: AJ
authors.lastname: van Beelen
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Zelinkova
authors.forename: Esther W
authors.initials: EW
authors.lastname: Taanman-Kueter
authors.forename: Femke J
authors.initials: FJ
authors.lastname: Muller
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Hommes
authors.forename: Sebastian A J
authors.initials: SA
authors.lastname: Zaat
authors.forename: Martien L
authors.initials: ML
authors.lastname: Kapsenberg
authors.forename: Esther C
authors.initials: EC
authors.lastname: de Jong
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001424:Bacterial Infections / Q000276:immunology*; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007156:Immunologic Memory; D007375:Interleukin-1 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D053473:Nod2 Signaling Adaptor Protein / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D020381:Interleukin-17; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018664:Interleukin-12; D000119:Acetylmuramyl-Alanyl-Isoglutamine