Toll-like receptor signalling
The human Toll-like receptor (TLR) family counts 10 members that sense specific pathogen associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPs). The TLR signalling cascade is mediated through the Toll/IL-1R (TIR)-adaptors MyD88, TIRAP/Mal, TRIF and TRAM. TLR signalling results in activation of transcription factors NFκB and AP-1 for induction of inflammatory cytokines, and/or interferon regulatory factors for induction of type I interferons.
The TLRs that recognize nucleic acids (TLR3, TLR7, TLR8, TLR9) are located on intracellular compartments, whereas TLR1, TLR2, TLR4, TLR5 and TLR6 are found both on the plasma membrane and on intracellular compartments.
Genetic approaches have been important for the discovery of TLRs and their signalling pathways. However, much less is known about how TLR signalling pathways are integrated into the cellular infrastructure in which they operate.
We hope to find new principles of TLR signalling from endosomes and phagosomes by using advanced cell biological methods that represent original approaches to the study of TLR signalling.