TLR Downstream Products

Description

Detection of PAMPs by TLRs represents the immune recognition step that accounts for self-nonself discrimination, triggers the innate immune response, and act as efficient molecules for priming and optimizing antigen specific adaptive host response. The TLR gene family and their pathways have been evolutionarily well conserved in both invertebrates and vertebrates. Among the various molecules involved in the successful coordination of the TLR pathway the most important is the adapter protein MyD88 that acts via IRAK1, IRAK2 and TRAF6. Stimulation of MyD88 leads to association with the IL-1R associated kinases, IRAK1, IRAK2 and IRAK4, where IRAK4 is regarded as the central mediator of TLR signaling which acts by activating IRAK1. Activation by these molecules leads to phosphorylation and degradation of IkB leading to the consequent release of NF-kB (p65) and NF-kB (p50). Thus stimulation of TLR by its cognate ligands leads to activation of the NF-kappa-B pathway, cytokine secretion and inflammatory response. TLR4 signaling may require additional molecules like MD-1, important for efficient CD180 cell surface expression and MD-2 to respond to LPS.

Bioinformatics

Alternate Names

Toll like receptors Toll-like receptors