Herpes simplex virus (HSV) initiates infection in mucosal epithelial cells, forming characteristic lesions before establishing lifelong latency in sensory neurons. The innate immune response to HSV is critically mediated by the Toll-like receptor (TLR) family. Expressed in a cell‑type‑specific manner, TLRs recognize viral components, leading to the production of interferons and pro-inflammatory cytokines. Different cell populations, by virtue of their unique TLR expression profiles and signaling contexts, mount specialized and non-redundant responses to the same viral pathogen. We systematically synthesize current research to elucidate the roles of specific TLRs in major cellular targets of HSV, including mucosal epithelial cells, fibroblasts, plasmacytoid dendritic cells, macrophages, peripheral neurons, and resident central nervous system cells. By examining how TLR-mediated sensing and signaling diverge across this cellular landscape, this article provides an integrated framework for understanding the coordinated, multi-layered immune defense against HSV and highlights the implications for pathogenesis and therapeutic strategies.
Yu et al. (Fri,) studied this question.