Critical role of IL-15-IL-15R for antigen-presenting cell functions in the innate immune response.
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.
Ohteki
T
T
Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Suzue
K
K
Maki
C
C
Ota
T
T
Koyasu
S
S
D000818:Animals; D019013:CD40 Antigens / Q000096:biosynthesis; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis / Q000494:pharmacology; D019409:Interleukin-15 / Q000235:genetics / Q000502:physiology*; D007376:Interleukin-2 / Q000235:genetics; D053646:Interleukin-2 Receptor beta Subunit; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000235:genetics; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D015854:Up-Regulation
D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II; C508025:Il15ra protein, mouse; C508022:Il2rb protein, mouse; D019409:Interleukin-15; D007376:Interleukin-2; D053646:Interleukin-2 Receptor beta Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma