Author: Zhang, S.-Y.; Jouanguy, E.; Ugolini, S.; Smahi, A.; Elain, G.; Romero, P.; Segal, D.; Sancho-Shimizu, V.; Lorenzo, L.; Puel, A.; Picard, C.; Chapgier, A.; Plancoulaine, S.; Titeux, M.; Cognet, C.; von Bernuth, H.; Ku, C.-L.; Casrouge, A.; Zhang, X.-X.; Barreiro, L.; Leonard, J.; Hamilton, C.; Lebon, P.; Heron, B.; Vallee, L.; Quintana-Murci, L.; Hovnanian, A.; Rozenberg, F.; Vivier, E.; Geissmann, F.; Tardieu, M.; Abel, L.; Casanova, J.-L.
Description: 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.
Subject headings: Alleles; CD8-Positive T-Lymphocytes/immunology; Cell Line; Child, Preschool; Dendritic Cells/immunology; Encephalitis, Herpes Simplex/genetics/immunology; Female; Fibroblasts/immunology/metabolism/virology; Genes, Dominant; Herpesvirus 1, Human/physiology; Heterozygote; Humans; Immunity, Innate; Infant; Interferons/biosynthesis; Keratinocytes/immunology; Killer Cells, Natural/immunology; Leukocytes, Mononuclear/immunology; Mutation; Poly I-C/pharmacology; Toll-Like Receptor 3/chemistry/deficiency/genetics/physiology
Publication year: 2007
Journal or book title: Science
Volume: 317
Issue: 5844
Pages: 1522-1527
Find the full text: https://www.science.org/doi/full/10.1126/science.1139522
Find more like this one (cited by): https://scholar.google.com/scholar?cites=17122416076756913923&as_sdt=1000005&sciodt=0,16&hl=en
Type: Journal Article
Serial number: 1730