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IFNgamma enhances IL-23 production during Francisella infection of human monocytes
Jonathan P Butchar1, Kishore V L Parsa, Clay B Marsh
1Division of Pulmonary and Critical Care, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA.
Abstract:
We previously demonstrated that monocytes produce IL-23 during Francisella infection, and that IL-23 induces IFNgamma from NK cells. Here, we demonstrate that IFNgamma-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 IFNgamma-treated monocytes revealed a significant induction of the IRFs. Interestingly, IFNgamma-primed monocytes produced IL-12 p70, a more potent inducer of IFNgamma than IL-23. We propose that there exists an amplification loop between monocyte IL-23 and NK/T cell IFNgamma that leads to IL-12 p70 production.
Insights
IFNgamma priming boosts monocyte IL-23 production during Francisella infection, creating an amplification loop that also stimulates IL-12 p70. This enhances the immune response by increasing IFNgamma. Keywords: IFNgamma, IL-23, IL-12 p70, Francisella infection, monocytes, immune response.
Area of Science:
- Immunology
- Microbiology
- Cellular Biology
Background:
- Monocytes are known to produce IL-23 during Francisella infection.
- IL-23 has been shown to induce IFNgamma production from NK cells.
Purpose of the Study:
- To investigate the effect of IFNgamma priming on monocyte IL-23 production during Francisella infection.
- To elucidate the mechanisms underlying enhanced IL-23 and IL-12 p70 production.
Main Methods:
- Monocyte cultures were primed with IFNgamma and subsequently infected with Francisella.
- Microarray analysis was performed on IFNgamma-treated monocytes.
- Cytokine levels (IL-12/23 p40 and IL-12 p70) were measured.
Main Results:
- IFNgamma priming significantly enhanced IL-23 production by monocytes during Francisella infection, specifically the IL-12/23 p40 subunit.
- Microarray analysis revealed significant induction of IRF-1 and IRF-8 transcription factors in IFNgamma-treated monocytes.
- IFNgamma-primed monocytes produced IL-12 p70, a potent inducer of IFNgamma, in addition to IL-23.
Conclusions:
- IFNgamma priming enhances monocyte IL-23 production during Francisella infection.
- An amplification loop involving monocyte-derived IL-23 and NK/T cell-derived IFNgamma may lead to increased IL-12 p70 production.
- This loop potentially amplifies the immune response to Francisella infection.
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