Critical role of IL-15-IL-15R for antigen-presenting cell functions in the innate immune response

Nat Immunol. 2001 Dec;2(12):1138-43. doi: 10.1038/ni729.


Activation of dendritic cells (DCs) and macrophages by infectious agents leads to secretion of interleukin 12 (IL-12), which subsequently induces interferon-gamma (IFN-gamma) production by multiple cell types that include DCs and macrophages. In turn, IFN-gamma acts on macrophages to augment IL-12 secretion and to produce nitric oxide (NO), which eradicates infected microbes. We show here that in cytokine common gamma subunit-deficient and/or IL-2 receptor beta-deficient mice, production of IL-12, IFN-gamma and NO by DCs and macrophages was severely impaired, as was up-regulation of major histocompatibility complex class II and CD40. Similar phenotypes were observed in DCs and macrophages from IL-15-deficient mice but not in those from IL-2-deficient mice. This shows that the IL-15-IL-15R interaction is critical in early activation of antigen-presenting cells and plays an important role in the innate immune system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD40 Antigens / biosynthesis
  • Cells, Cultured
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Histocompatibility Antigens Class II / biosynthesis
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / pharmacology
  • Interleukin-15 / genetics
  • Interleukin-15 / physiology*
  • Interleukin-2 / genetics
  • Interleukin-2 Receptor beta Subunit
  • Macrophages / drug effects
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitric Oxide / biosynthesis
  • RNA, Messenger / biosynthesis
  • Receptors, Interleukin / biosynthesis
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin-15
  • Receptors, Interleukin-2 / physiology*
  • Up-Regulation


  • CD40 Antigens
  • Histocompatibility Antigens Class II
  • Il15ra protein, mouse
  • Il2rb protein, mouse
  • Interleukin-15
  • Interleukin-2
  • Interleukin-2 Receptor beta Subunit
  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-15
  • Receptors, Interleukin-2
  • Interleukin-12
  • Nitric Oxide
  • Interferon-gamma