Community Research and Development Information Service - CORDIS


Final Report - TOLLICOR (Dissecting pathogen recognition complexes of Toll-like receptors: hunting for new co-receptors and ligands)

Project ID: 220596
Funded under: FP7-PEOPLE


Toll-like receptors (TLRs) are trans-membrane proteins that recognise pathogen associated molecular patterns (PAMPs) and subsequently induce an intracellular signalling cascade that triggers the activation of transcription factors which initiate the expression of host defence proteins. The objective of this project was to identify TLR co-receptor complexes required for viral response in mouse macrophages via tandem affinity purification (TAP).

In this final report, they explain how, in order to broaden their understanding on the mechanisms of TLR action and pathogen recognition they set out to identify novel interactors of endosomal TLRs. To this end they cloned tagged versions of murine endosomal TLRs and transduced them into RAW264.7 murine macrophages. Tandem affinity purification with those receptors was performed and enriched receptor complexes were then analysed by mass spectrometry. Using the support of our bioinformatics department seven high confidence interacting proteins were selected for further validation as putative novel interactors of endosomal TLRs. Further interactors found in the TOLLLICOR screen are under investigation.

The report ends by noting that they have also shown that soluble recombinant CD14 protein can enhance endosomal TLR activation, in addition, a monoclonal antibody that binds to the ectodomain of CD14 can block such response. These are potential therapheutic approaches in the modulation of endosomal TLR signalling.

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