Nod1 and Nod2 enhance TLR-mediated invariant NKT cell activation during bacterial infection

J Immunol. 2013 Dec 1;191(11):5646-54. doi: 10.4049/jimmunol.1301412. Epub 2013 Oct 25.


Invariant NKT (iNKT) cells act at the crossroad between innate and adaptive immunity and are important players in the defense against microbial pathogens. iNKT cells can detect pathogens that trigger innate receptors (e.g., TLRs, Rig-I, Dectin-1) within APCs, with the consequential induction of CD1d-mediated Ag presentation and release of proinflammatory cytokines. We show that the cytosolic peptidoglycan-sensing receptors Nod1 and Nod2 are necessary for optimal IFN-γ production by iNKT cells, as well as NK cells. In the absence of Nod1 and Nod2, iNKT cells had a blunted IFN-γ response following infection by Salmonella enterica serovar Typhimurium and Listeria monocytogenes. For Gram-negative bacteria, we reveal a synergy between Nod1/2 and TLR4 in dendritic cells that potentiates IL-12 production and, ultimately, activates iNKT cells. These findings suggest that multiple innate pathways can cooperate to regulate iNKT cell activation during bacterial infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Dendritic Cells / immunology
  • Dendritic Cells / microbiology
  • Immunity, Innate / genetics
  • Interferon-gamma / metabolism
  • Interleukin-12 / metabolism
  • Listeria monocytogenes / immunology*
  • Listeriosis / immunology*
  • Lymphocyte Activation / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Natural Killer T-Cells / immunology*
  • Nod1 Signaling Adaptor Protein / genetics
  • Nod1 Signaling Adaptor Protein / metabolism*
  • Nod2 Signaling Adaptor Protein / genetics
  • Nod2 Signaling Adaptor Protein / metabolism*
  • Salmonella typhi / immunology*
  • Toll-Like Receptor 4 / metabolism
  • Typhoid Fever / immunology*


  • Nod1 Signaling Adaptor Protein
  • Nod1 protein, mouse
  • Nod2 Signaling Adaptor Protein
  • Nod2 protein, mouse
  • Toll-Like Receptor 4
  • Interleukin-12
  • Interferon-gamma