TLR3 and herpes simplex encephalitis: Later, the identification of a heterozygous mutation within the predicted dsRNA binding cleft of TLR3 discovered in two unrelated children with HSE, together with HSV-1 infection experiments in neuronal cells reprogrammed from induced pluripotent stem cells (iPSCs) generated from these HSE patients, highlighted that TLR3 signaling is essential within the CNS compartment upon HSV-1 encounter [49, 50] (Fig. 2).