Cutting edge: a murine, IL-12-independent pathway of IFN-gamma induction by gram-negative bacteria based on STAT4 activation by Type I IFN and IL-18 signaling.
IFN-alphabeta is a potent immunoregulatory cytokine involved in the defense against viral and bacterial infections. In this study, we describe an as yet undefined IFN-alphabeta-dependent pathway of IFN-gamma induction in mice. This pathway is based on a synergism of IFN-alphabeta and IL-18, and is independent of IL-12 signaling yet dependent on STAT4. In contradiction to current dogma, we show further that IFN-alphabeta alone induces tyrosine phosphorylation of STAT4 in murine splenocytes of different mouse strains. This pathway participates in the induction of IFN-gamma by Gram-negative bacteria and is therefore expected to play a role whenever IFN-alpha or IFN-beta and IL-18 are produced concomitantly during bacterial, viral, or other infections.
Freudenberg
Marina A
MA
Max-Planck-Institut für Immunbiologie, Freiburg, Germany. freudenberg@immunbio.mpg.de
Merlin
Thomas
T
Kalis
Christoph
C
Chvatchko
Yolande
Y
Stübig
Hella
H
Galanos
Chris
C
D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006090:Gram-Negative Bacteria / Q000276:immunology / Q000472:pathogenicity*; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000378:metabolism*; D016899:Interferon-beta / Q000378:metabolism*; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D050797:STAT4 Transcription Factor; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D020382:Interleukin-18; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D015534:Trans-Activators; D018664:Interleukin-12; D014443:Tyrosine; D016899:Interferon-beta; D007371:Interferon-gamma