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Cutting Edge: A Murine, IL-12-Independent Pathway of IFN-γ Induction by Gram-Negative: Bacteria Based on STAT4 Activation by Type I IFN and IL-18 Signaling¹

By M. Freudenberg, T. Merlin, C. Kalis, Y. Chvatchko, H. Stübig and C. Galanos


IFN-αβ is a potent immunoregulatory cytokine involved in the defense against viral and bacterial infections. In this study, we describe an as yet undefined IFN-αβ-dependent pathway of IFN-γ induction in mice. This pathway is based on a synergism of IFN-αβ and IL-18, and is independent of IL-12 signaling yet dependent on STAT4. In contradiction to current dogma, we show further that IFN-αβ alone induces tyrosine phosphorylation of STAT4 in murine splenocytes of different mouse strains. This pathway participates in the induction of IFN-γ by Gram-negative bacteria and is therefore expected to play a role whenever IFN-α or IFN-β and IL-18 are produced concomitantly during bacterial, viral, or other infections

Year: 2002
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Provided by: MPG.PuRe
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