title: Synergistic interaction between Toll-like receptor agonists is required for induction of experimental autoimmune encephalomyelitis in Lewis rats.
abstract: To investigate whether TLR agonists can replace mycobacteria in adjuvant to induce EAE in Lewis rats, we immunized rats with MBP peptide (MBP(68-86)) in IFA, supplemented with TLR agonists. Rats immunized with MBP(68-86) plus CpG-ODN or LPS in IFA did not develop EAE. In contrast, rats immunized with MBP(68-86) plus CpG-ODN and LPS in IFA developed clinical EAE. Spleen cells proliferated and secreted IFN-gamma in response to MBP(68-86), and secreted IL-6 and IL-12p40 in response to CpG-ODN and LPS. However, rats immunized with MBP(68-86) plus CpG-ODN and PolyI:C, a TLR3 agonist, did not develop EAE. We conclude that selected combinations of TLR agonists can facilitate the induction of EAE by MBP peptide via the innate immune system.
authors.affiliation: Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Norbert A
authors.initials: NA
authors.lastname: Wolf
authors.forename: Taba K
authors.initials: TK
authors.lastname: Amouzegar
authors.forename: Robert H
authors.initials: RH
authors.lastname: Swanborg
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D015153:Blotting, Western; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007369:Interferon Inducers / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D011070:Poly I-C / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D051193:Toll-Like Receptors / Q000819:agonists*
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D007369:Interferon Inducers; D015850:Interleukin-6; D008070:Lipopolysaccharides; D004676:Myelin Basic Protein; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; D051193:Toll-Like Receptors; C110235:myelin basic protein 68-86; D018664:Interleukin-12; D007371:Interferon-gamma; D011070:Poly I-C