Toll-like receptors as adjuvant receptors.
The mammalian Toll-like receptors (TLRs) are expressed on macrophages and dendritic cells, which are primarily involved in innate immunity. At present, ligands for several of the TLRs, such as TLR2, TLR3, TLR4, TLR5, TLR6, and TLR9, have been identified. Most of these ligands are derived from pathogens, but not found in the host, suggesting that the TLRs are critical to sensing invading microorganisms. Pathogen recognition by TLRs provokes rapid activation of innate immunity by inducing production of proinflammatory cytokines and upregulation of costimulatory molecules. Activated innate immunity subsequently leads to effective adaptive immunity. In this regard, the TLRs are considered to be adjuvant receptors. Distinct TLRs can exert distinct, but overlapping sets of biological effects. Accumulating evidence indicates that this can be attributed to both the common and unique aspects of the signaling mechanisms that mediate TLR family responses. For example, TLR2 and TLR9 require MyD88 as an essential signal transducer, whereas TLR4 can induce costimulatory molecule upregulation in a MyD88-independent manner. Understanding the TLR system should offer invaluable opportunity for manipulating host immune responses.
Kaisho
Tsuneyasu
T
Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
Akira
Shizuo
S
D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic / Q000378:metabolism*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000943:Antigens, Differentiation / Q000378:metabolism; D001419:Bacteria / Q000472:pathogenicity; D018899:CpG Islands; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D029721:Drosophila Proteins; D006801:Humans; D007109:Immunity; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D051200:Toll-Like Receptor 8; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors
D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic; D000943:Antigens, Differentiation; D016207:Cytokines; D029721:Drosophila Proteins; D008024:Ligands; D008070:Lipopolysaccharides; C507779:MYD88 protein, human; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C495342:TLR2 protein, human; C495344:TLR3 protein, human; C495345:TLR4 protein, human; C495346:TLR5 protein, human; C495349:TLR8 protein, human; C495371:TLR9 protein, human; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D051200:Toll-Like Receptor 8; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors