title: TLR2 & Co: a critical analysis of the complex interactions between TLR2 and coreceptors.
abstract: TLRs play a major role in microbe-host interactions and innate immunity. Of the 10 functional TLRs described in humans, TLR2 is unique in its requirement to form heterodimers with TLR1 or TLR6 for the initiation of signaling and cellular activation. The ligand specificity of TLR2 heterodimers has been studied extensively, using specific bacterial and synthetic lipoproteins to gain insight into the structure-function relationship, the minimal active motifs, and the critical dependence on TLR1 or TLR6 for activation. Different from that for specific well-defined TLR2 agonists, recognition of more complex ligands like intact microbes or molecules from endogenous origin requires TLR2 to interact with additional coreceptors. A breadth of data has been published on ligand-induced interactions of TLR2 with additional pattern recognition receptors such as CD14, scavenger receptors, integrins, and a range of other receptors, all of them important factors in TLR2 function. This review summarizes the roles of TLR2 in vivo and in specific immune cell types and integrates this information with a detailed review of our current understanding of the roles of specific coreceptors and ligands in regulating TLR2 functions. Understanding how these processes affect intracellular signaling and drive functional immune responses will lead to a better understanding of host-microbe interactions and will aid in the design of new agents to target TLR2 function in health and disease.
authors.affiliation: 1.PO Box 80141, 3508 TC Utrecht, The Netherlands. jeroen.vanbergen@danone.com.
authors.forename: Jeroen
authors.initials: J
authors.lastname: van Bergenhenegouwen
authors.forename: Theo S
authors.initials: TS
authors.lastname: Plantinga
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.forename: Gert
authors.initials: G
authors.lastname: Folkerts
authors.forename: Aletta D
authors.initials: AD
authors.lastname: Kraneveld
authors.forename: Johan
authors.initials: J
authors.lastname: Garssen
authors.forename: Arjan P
authors.initials: AP
authors.lastname: Vos
mesh_terms: D000818:Animals; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D016023:Integrins / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins; D037102:Lectins / Q000502:physiology; D018950:Lipopolysaccharide Receptors / Q000502:physiology; D008070:Lipopolysaccharides / Q000502:physiology; D021962:Membrane Microdomains / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D055503:Protein Multimerization; D019718:Receptors, CXCR4 / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology*; D051192:Receptors, Pattern Recognition / Q000502:physiology; D051116:Receptors, Scavenger / Q000502:physiology; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*
chemical_list: D018836:Inflammation Mediators; D016023:Integrins; D036341:Intercellular Signaling Peptides and Proteins; D037102:Lectins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D019718:Receptors, CXCR4; D011971:Receptors, Immunologic; D051192:Receptors, Pattern Recognition; D051116:Receptors, Scavenger; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; C517340:ZG16B protein, human; C009900:lipoteichoic acid
keywords: DAMP; MAMP; TLR2 function; pattern recognition receptor; toll like receptor