TLR3 deficiency in patients with herpes simplex encephalitis

SY Zhang, E Jouanguy, S Ugolini, A Smahi, G Elain… - science, 2007 - science.org
SY Zhang, E Jouanguy, S Ugolini, A Smahi, G Elain, P Romero, D Segal, V Sancho-Shimizu
science, 2007science.org
Some Toll and Toll-like receptors (TLRs) provide immunity to experimental infections in
animal models, but their contribution to host defense in natural ecosystems is unknown. We
report a dominant-negative TLR3 allele in otherwise healthy children with herpes simplex
virus 1 (HSV-1) encephalitis. TLR3 is expressed in the central nervous system (CNS), where
it is required to control HSV-1, which spreads from the epithelium to the CNS via cranial
nerves. TLR3 is also expressed in epithelial and dendritic cells, which apparently use TLR3 …
Some Toll and Toll-like receptors (TLRs) provide immunity to experimental infections in animal models, but their contribution to host defense in natural ecosystems is unknown. We report a dominant-negative TLR3 allele in otherwise healthy children with herpes simplex virus 1 (HSV-1) encephalitis. TLR3 is expressed in the central nervous system (CNS), where it is required to control HSV-1, which spreads from the epithelium to the CNS via cranial nerves. TLR3 is also expressed in epithelial and dendritic cells, which apparently use TLR3-independent pathways to prevent further dissemination of HSV-1 and to provide resistance to other pathogens in TLR3-deficient patients. Human TLR3 appears to be redundant in host defense to most microbes but is vital for natural immunity to HSV-1 in the CNS, which suggests that neurotropic viruses have contributed to the evolutionary maintenance of TLR3.
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