Signal integration between IFNγ and TLR signalling pathways in macrophages

Macrophages are major effector cells of the innate immune system, and appropriate regulation of macrophage function requires the integration of multiple signalling inputs derived from the recognition of host factors (e.g. interferon-γ/IFNγ) and pathogen products (e.g. toll-like receptor/TLR agonists). The profound effects of IFNγ pre-treatment (“priming”) on TLR-induced macrophage activation have long been recognised, but many of the mechanisms underlying the priming phenotype have only recently been identified. This review summarises the known mechanisms of integration between the IFNγ and TLR signalling pathways. Synergy occurs at multiple levels, ranging from signal recognition to convergence of signals at the promoters of target genes. In particular, the cross-talk between the IFNγ, and LPS and CpG DNA signalling pathways is discussed.