Cutting edge: identification of c-Rel-dependent and -independent pathways of IL-12 production during infectious and inflammatory stimuli.
The production of IL-12 is required for immunity to many intracellular pathogens. Recent studies have shown that c-Rel, a member of the NF-kappaB family of transcription factors, is essential for LPS-induced IL-12p40 production by macrophages. In this study, we demonstrate that c-Rel is also required for IL-12p40 production by macrophages in response to Corynebacterium parvum, CpG oligodeoxynucleotides, anti-CD40 and low molecular weight hyaluronic acid. However, c-Rel(-/-) mice infected with Toxoplasma gondii produce comparable amounts of IL-12p40 to infected wild-type mice and have an IL-12-dependent mechanism of resistance to this infection. Furthermore, c-Rel was not required for IL-12p40 production by macrophages or dendritic cells in response to soluble Toxoplasma Ag, and neutrophils from c-Rel(-/-) mice contain normal amounts of preformed IL-12p40. Together these studies reveal the presence of c-Rel-dependent pathways critical for IL-12p40 production in response to inflammatory stimuli and demonstrate a novel c-Rel-independent pathway of IL-12p40 production during toxoplasmosis.
Mason
Nicola
N
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Aliberti
Julio
J
Caamano
Jorge C
JC
Liou
Hsiou-Chi
HC
Hunter
Christopher A
CA
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control
D008070:Lipopolysaccharides; D020569:Proto-Oncogene Proteins c-rel; D018664:Interleukin-12