Multiple toll-like receptor agonists act as potent adjuvants in the induction of autoimmunity.
Infections can trigger or exacerbate the course of Multiple Sclerosis, and both bacterial and viral agents have been implicated. These agents are recognized by host cells via pathogen-associated molecular patterns activating TLRs. We investigated the role that PAMPs play in the animal model Experimental Autoimmune Encephalomyelitis, and found various MyD88-dependent PAMPs can participate as the adjuvant to induce EAE. Studies with IRAK1-deficient mice suggest that signaling through TLRs is not required in the target organ to develop disease. This suggests that PAMPs play an important role in priming of autoreactive T cells in EAE and potentially MS.
Hansen
Baranda S
BS
Department of Neurology, UT Southwestern Medical Center, 5323 Harry Hines Blvd. Dallas, TX 75390, USA.
Hussain
Rehana Z
RZ
Lovett-Racke
Amy E
AE
Thomas
James A
JA
Racke
Michael K
MK
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000277:Adjuvants, Pharmaceutic / Q000494:pharmacology*; D000818:Animals; D015551:Autoimmunity / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced*; D006023:Glycoproteins / Q000494:pharmacology; D053592:Interleukin-1 Receptor-Associated Kinases; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein; D053594:Myeloid Differentiation Factor 88; D010446:Peptide Fragments / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency; D013154:Spleen / Q000473:pathology; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D051193:Toll-Like Receptors / Q000819:agonists*; D014316:Tritium / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D000277:Adjuvants, Pharmaceutic; D016207:Cytokines; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; C507780:Myd88 protein, mouse; D063308:Myelin-Oligodendrocyte Glycoprotein; D053594:Myeloid Differentiation Factor 88; D010446:Peptide Fragments; D051193:Toll-Like Receptors; C445081:myelin oligodendrocyte glycoprotein (35-55); D014316:Tritium; D053592:Interleukin-1 Receptor-Associated Kinases; C507769:Irak1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D013936:Thymidine