The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling
The function of the fifth adaptor, SARM, has been revealed, which negatively regulates TRIF, and it is shown that it acts as a bridging adaptor in the initiation of TLR signalling.
IFI16 is an innate immune sensor for intracellular DNA
IFI16 (p204) is the first PYHIN protein to their knowledge shown to be involved in IFN-β induction and forms a new family of innate DNA sensors the authors call 'AIM2-like receptors' (ALRs).
The history of Toll-like receptors — redefining innate immunity
Toll-like receptors have a central role in immunity — in this Timeline article, the landmark findings that gave rise to this important field of research are described.
Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction
A protein is described, Mal (MyD88-adapter-like), which joins MyD88 as a cytoplasmic TIR-domain-containing protein in the human genome, which is therefore an adapter in TLR-4 signal transduction.
The human adaptor SARM negatively regulates adaptor protein TRIF–dependent Toll-like receptor signaling
- M. Carty, R. Goodbody, M. Schröder, J. Stack, P. Moynagh, A. Bowie
- BiologyNature Immunology
- 10 September 2006
The fifth mammalian TIR adaptor SARM is a negative regulator of Toll-like receptor signaling, and 'knockdown' of endogenous SARM expression by interfering RNA led to enhanced TRIF-dependent cytokine and chemokine induction.
Immune sensing of DNA.
Structures of the HIN domain:DNA complexes reveal ligand binding and activation mechanisms of the AIM2 inflammasome and IFI16 receptor.
Vaccinia virus protein A46R targets multiple Toll-like–interleukin-1 receptor adaptors and contributes to virulence
The function of the vaccinia virus (VV) protein A46R is defined and it is shown it inhibits intracellular signalling by a range of Toll-like receptors (TLRs) and is functionally distinct from another described VV TLR inhibitor, A52R.
A46R and A52R from vaccinia virus are antagonists of host IL-1 and toll-like receptor signaling.
- A. Bowie, E. Kiss-Toth, J. Symons, G. Smith, S. Dower, L. O’Neill
- BiologyProceedings of the National Academy of Sciences…
- 29 August 2000
Two vaccinia virus ORFs are identified, termed A46R and A52R, that share amino acid sequence similarity with the Toll/IL-1 receptor (TIR) domain, a motif that defines the IL-1/Toll-like receptor (TLR) superfamily of receptors, which have a key role in innate immunity and inflammation.
Viral targeting of DEAD box protein 3 reveals its role in TBK1/IKKε‐mediated IRF activation
A novel VACV protein, K7, is described, which can inhibit PRR‐induced IFN‐β induction by preventing TBK1/IKKε‐mediated IRF activation and Ifnb promoter induction.