IFNγ enhances IL-23 production during Francisella infection of human monocytes

We previously demonstrated that monocytes produce IL-23 during Francisella infection, and that IL-23 induces IFN gamma from NK cells. Here, we demonstrate that IFN gamma-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 IFN gamma-treated monocytes revealed a significant induction of the IRFs. Interestingly, IFN gamma-primed monocytes produced IL-12 p70, a more potent inducer of IFN gamma than IL-23. We propose that there exists an amplification loop between monocyte IL-23 and NK/T cell IFN gamma that leads to IL-12 p70 production. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.