title: Advances in Toll-like receptor biology: Modes of activation by diverse stimuli.
abstract: As we learn more about the biology of the Toll-like receptors (TLRs), a wide range of molecules that can activate this fascinating family of pattern recognition receptors emerges. In addition to conserved pathogenic components, endogenous danger signals created upon tissue damage are also sensed by TLRs. Detection of these types of stimuli results in TLR mediated inflammation that is vital to fight pathogenic invasion and drive tissue repair. Aberrant activation of TLRs by pathogenic and endogenous ligands has also been linked with the pathogenesis of an increasing number of infectious and autoimmune diseases, respectively. Most recently, allergen activation of TLRs has also been described, creating a third broad class of TLR stimulus that has helped to shed light on the pathogenesis of allergic disease. To date, microbial activation of TLRs remains best characterized. Each member of the TLR family senses a specific subset of pathogenic ligands, pathogen associated molecular patterns (PAMPS), and a wealth of structural and biochemical data continues to reveal the molecular mechanisms of TLR activation by PAMPs, and to demonstrate how receptor specificity is achieved. In contrast, the mechanisms by which endogenous molecules and allergens activate TLRs remain much more mysterious. Here, we provide an overview of our current knowledge of how very diverse stimuli activate the same TLRs and the structural basis of these modes of immunity.
authors: a Department of Veterinary Medicine and.
authors: Clare E
authors: CE
authors: Bryant
authors: b Department of Biochemistry , University of Cambridge , Cambridge , UK .
authors: Nick J
authors: NJ
authors: Gay
authors: c Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, University of Leuven , Leuven , Belgium .|d ICIN - Netherlands Heart Institute , Utrecht , The Netherlands .
authors: Stephane
authors: S
authors: Heymans
authors: e Brighton & Sussex Medical School, University of Sussex , Brighton , UK .
authors: Sandra
authors: S
authors: Sacre
authors: f Pharmazentrum Frankfurt/ZAFES, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der Goethe-Universität Frankfurt am Main , Frankfurt am Main , Germany , and.
authors: Liliana
authors: L
authors: Schaefer
authors: g Nuffield Department of Orthopaedics , Rheumatology and Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford , Oxford , UK.
authors: Kim S
authors: KS
authors: Midwood
mesh_terms: D000485:Allergens / Q000378:metabolism; D000818:Animals; D015551:Autoimmunity; D005109:Extracellular Matrix / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D008024:Ligands; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008954:Models, Biological; D011487:Protein Conformation; D020033:Protein Isoforms; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000819:agonists* / Q000737:chemistry / Q000378:metabolism
chemical_list: D000485:Allergens; D008024:Ligands; D020033:Protein Isoforms; D051193:Toll-Like Receptors
keywords: Allergens; Toll-like receptors; endogenous stimuli; extracellular matrix; glycoproteins; nucleic acids; pathogen recognition; small leucine rich proteoglycans; structure