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Cytokines Involved in Interferon-γ Production by Human Macrophages

2009; Karger Publishers; Volume: 2; Issue: 1 Linguagem: Inglês

10.1159/000247156

1662-8128

Cory M. Robinson, Dawn M. O’Dee, T. Hamilton, Gerard J. Nau,

Immune Response and Inflammation

Interferon (IFN)-γ is important to the immune defense against intracellular pathogens and specifically the ability of macrophages to control <i>Mycobacterium tuberculosis</i> (MTB). Increasing evidence has accumulated to support the idea that macrophages produce IFN-γ. We describe here the cytokine interactions that determine IFN-γ expression and secretion during MTB infection of human macrophages. Detection of biologically important IFN-γ levels in culture supernatants of MTB-infected human macrophages requires the addition of interleukin (IL)-12. IL-18 augmented IFN-γ production from human macrophages in response to the combination of MTB and supplemental IL-12. Although IL-18 gene expression was generally unchanged, IL-18 protein secretion was enhanced by the combination of MTB and IL-12, and functioned primarily to stimulate IFN-γ release. Importantly, IL-27 induced by MTB infection opposed IFN-γ production by antagonizing IL-18 activity in human macrophages. Neutralization of IL-27 increased the expression of the IL-18 receptor β-chain. Additionally, IL-27 blocked NF-ĸB activation in response to IL-18. These results define the signals required for IFN-γ production by human macrophages and highlight the interactions between cytokines produced during MTB infection. Together, they identify a novel role for IL-27 in regulating macrophage function by disrupting IL-18 activity.