Toll-like receptors in multiple sclerosis mouse experimental models.
Certain pathogen molecules trigger innate immune responses and drive subsequent adaptive immune responses toward an antigen presented simultaneously. Such bacterial or viral molecules constitute pathogen-associated molecular patterns (PAMPs) that bind to pattern-recognition receptors such as toll-like receptors (TLRs). Recently, endogenous molecules were identified that ligate the same receptors. The role of these receptors' response to complete Freund's adjuvant during initiation of CD4 T cell responses in EAE, the animal model for multiple sclerosis, is here discussed. Myeloid differentiation primary response gene 88 (MyD88) is necessary for the induction of experimental autoimmune encephalomyelitis (EAE), and it is required for the activation of myeloid dendritic cells and differentiation of T helper 17 cells. The role of individual TLR, in particular TLR3, TLR4, and TLR9, signaling in modulation of EAE inflammation varies with the experimental model employed and the immune cells that drive pathology. The TLR-dependent production of proinflammatory cytokines is regulated by mechanisms that dampen the pathway and prevent excess damage. Development of TLR antagonists to treat autoimmune diseases must acknowledge the possibility of interference with regulatory mechanisms.
Marta
Monica
M
Neuroimmunology, Neuroscience Centre, ICMS, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. m.calado-marta@qmul.ac.uk
D000818:Animals; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology*; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology*
D020381:Interleukin-17; D053594:Myeloid Differentiation Factor 88; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9