Coordinating TLR-activated signaling pathways in cells of the immune system

Toll-like receptor (TLR) signaling leads to the activation of mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways. While the upstream signaling events initiated at the level of adaptors and the activation of the downstream signaling pathways have received a lot of attention, our understanding of how these signaling pathways are coordinated to regulate gene expression is poorly understood. This review gives a selective overview on our current understanding of signaling downstream of TLRs, with an emphasis on how the upstream kinases like the mitogen-activated protein kinase kinase kinases (TAK1 and Tpl2) and inhibitor of kappa-B kinase (IKK) coordinate the signaling events that steer the course of an immune response.