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Abstract: We previously demonstrated that monocytes produce IL-23 during Francisella infection, and that IL-23 induces IFNγ from NK cells. Here, we demonstrate that IFNγ-priming of monocytes enhances IL-23 production during Francisella infection. This effect was seen on the IL12/23 p40 subunit. Induction of IL-12/23 p40 is reported to be enhanced by IRF-1 and IRF-8. Consistently, microarray analysis of IFNγ-treated monocytes revealed a significant induction of the IRFs. Interestingly, IFNγ-primed monocytes produced IL-12 p70, a more potent inducer of IFNγ than IL-23. We propose that there exists an amplification loop between monocyte IL-23 and NK/T cell IFNγ that leads to IL-12 p70 production. [Copyright &y& Elsevier]