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Cutting Edge |
Induction by Gram-Negative Bacteria Based on STAT4 Activation by Type I IFN and IL-18 Signaling1
* Max-Planck-Institut für Immunbiologie, Freiburg, Germany; and
Serono Pharmaceutical Research Institute, Geneva, Switzerland
IFN-
is a potent immunoregulatory cytokine involved
in the defense against viral and bacterial infections. In this study,
we describe an as yet undefined IFN--dependent pathway of IFN-
induction in mice. This pathway is based on a synergism of IFN-
and IL-18, and is independent of IL-12 signaling yet dependent
on STAT4. In contradiction to current dogma, we show further that
IFN- alone induces tyrosine phosphorylation of
STAT4 in murine splenocytes of different mouse strains. This pathway
participates in the induction of IFN- by Gram-negative bacteria and
is therefore expected to play a role whenever IFN- or IFN- and
IL-18 are produced concomitantly during bacterial, viral, or other
infections.
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