Poly(I:C) promotes TNFa/TNFR1-dependent oligodendrocyte death in mixed glial cultures

Steelman, Andrew J; Li, Jianrong

Toll-like receptor expression is not equally represented across different populations of resident CNS cells. Since TLR3, a recognition receptor for double-stranded RNA viruses, is present in all glia, the current study tested the hypothesis that stimulation of mixed glia with the TLR3 ligand poly(I:C) would exhibit different outcomes than those following LPS stimulation. Utilizing poly(I:C) to model the bystander effects of glial activation on preOL viability following RNA viral infection, we found that over-activation of glia, specifically microglia, reduced preOL viability in mixed glial cultures. Mechanistically, this toxicity was dependent on TNFα/TNFR1 signaling. Extending on these findings we observed that activation of TLR1/2 and TLR7/8 had similar effects on preOLs. Thus, our data indicate that uncontrolled production of TNFα in the CNS upon viral infection may consequentially contribute to oligodendrocyte death and demyelination.