Stimulation of the intracellular bacterial sensor NOD2 programs dendritic cells to promote interleukin-17 production in human memory T cells

Immunity. 2007 Oct;27(4):660-9. doi: 10.1016/j.immuni.2007.08.013. Epub 2007 Oct 4.


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.

MeSH terms

  • Acetylmuramyl-Alanyl-Isoglutamine / immunology
  • Animals
  • Antigen Presentation / immunology
  • Bacterial Infections / immunology*
  • Crohn Disease / genetics
  • Crohn Disease / immunology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunologic Memory*
  • Interleukin-1 / immunology
  • Interleukin-12 / immunology
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / immunology
  • Lymphocyte Activation / immunology
  • Mice
  • Nod2 Signaling Adaptor Protein / immunology*
  • Nod2 Signaling Adaptor Protein / metabolism
  • RNA, Messenger
  • RNA, Small Interfering
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism


  • Interleukin-1
  • Interleukin-17
  • NOD2 protein, human
  • Nod2 Signaling Adaptor Protein
  • RNA, Messenger
  • RNA, Small Interfering
  • Interleukin-12
  • Acetylmuramyl-Alanyl-Isoglutamine