Fig. 1
(Adapted from Bustamante et al. [2]). RORC, SPPL2A, L23R and their protein products are not indicated in this figure but have also been implicated in MSMD and IFN-γ-mediated immunity)
The IL-12-IFN-γ cytokine pathways. The IFN-γ-IL-12 pathway is involved in the host response to infection with certain intracellular viral and bacterial pathogens such as Mycobacteria and Salmonella. Upon recognition of the pathogen (indicated in red), phagocytes (such as macrophages and dendritic cells (DCs)) secrete IL-12 which bind to their receptors on T lymphocytes and NK cells, inducing the production of IFN-γ. IL-12 production is enhanced by a CD40-triggered, NEMO/NFκB-dependent pathway. The proteins encoded by genes that have been associated with MSMD are indicated in blue. Mutations in IFNGR1, IFNGR2, CYBB, STAT1, JAK1 and IRF8 impair the action of IFN-γ while mutations in IL12B, IL12RB1, IL12RB2, ISG15, IKBKG (NEMO) and IRF8 impairs the function of IFN-γ.