Fig. 1.

a Timeline of TLR2 tolerance induction. Timeline for the 5-week induction of demyelination with 0.2% cuprizone (or normal chow), followed by the 2-week remyelination period on normal chow. WT mice were treated with either low dose P2C or VC during the remyelination period. Mice were sacrificed and analyzed after the 2-week remyelination period. b Timeline of TLR2^−/−. Timeline for the 5-week induction of demyelination with 0.2% cuprizone (or normal chow) followed by the 2-week remyelination period. WT and TLR2^−/− mice were not treated during the remyelination period. Mice were sacrificed and analyzed immediately following the 5-week cuprizone (or normal chow) feeding to evaluate baseline demyelination levels, or after the 2-week remyelination period on normal chow to evaluate myelin recovery. c Systemic TLR2 tolerance induction. At the end of the 2-week remyelination period, WT mice that had been fed for the first 5 weeks with either cuprizone or normal chow and treated with P2C or VC as in a received a single i.v. injection of Pam3CSK₄ (P3C, 100 μg) and 2 h later serum was obtained and analyzed for TNFα by ELISA. Results are expressed as mean values per mouse. N = 9 mice/cohort. Error bars represent the mean ± SEM. Statistical differences were assessed by 2-way ANOVA. ****p < 0.0001. For NS comparisons, VC treated: normal vs cuprizone-fed, p = 0.8118. P2C treated: normal vs cuprizone-fed, p = 0.9972