title: TLR3 deficiency in patients with herpes simplex encephalitis.
abstract: 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.
authors.affiliation: Human Genetics of Infectious Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM), U550, Faculty Necker, Paris 75015, France.
authors.forename: Shen-Ying
authors.initials: SY
authors.lastname: Zhang
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Jouanguy
authors.forename: Sophie
authors.initials: S
authors.lastname: Ugolini
authors.forename: Asma
authors.initials: A
authors.lastname: Smahi
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Elain
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.forename: David
authors.initials: D
authors.lastname: Segal
authors.forename: Vanessa
authors.initials: V
authors.lastname: Sancho-Shimizu
authors.forename: Lazaro
authors.initials: L
authors.lastname: Lorenzo
authors.forename: Anne
authors.initials: A
authors.lastname: Puel
authors.forename: Capucine
authors.initials: C
authors.lastname: Picard
authors.forename: Ariane
authors.initials: A
authors.lastname: Chapgier
authors.forename: Sabine
authors.initials: S
authors.lastname: Plancoulaine
authors.forename: Matthias
authors.initials: M
authors.lastname: Titeux
authors.forename: Céline
authors.initials: C
authors.lastname: Cognet
authors.forename: Horst
authors.initials: H
authors.lastname: von Bernuth
authors.forename: Cheng-Lung
authors.initials: CL
authors.lastname: Ku
authors.forename: Armanda
authors.initials: A
authors.lastname: Casrouge
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Zhang
authors.forename: Luis
authors.initials: L
authors.lastname: Barreiro
authors.forename: Joshua
authors.initials: J
authors.lastname: Leonard
authors.forename: Claire
authors.initials: C
authors.lastname: Hamilton
authors.forename: Pierre
authors.initials: P
authors.lastname: Lebon
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Héron
authors.forename: Louis
authors.initials: L
authors.lastname: Vallée
authors.forename: Lluis
authors.initials: L
authors.lastname: Quintana-Murci
authors.forename: Alain
authors.initials: A
authors.lastname: Hovnanian
authors.forename: Flore
authors.initials: F
authors.lastname: Rozenberg
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.forename: Frédéric
authors.initials: F
authors.lastname: Geissmann
authors.forename: Marc
authors.initials: M
authors.lastname: Tardieu
authors.forename: Laurent
authors.initials: L
authors.lastname: Abel
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
mesh_terms: D000483:Alleles; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002675:Child, Preschool; D003713:Dendritic Cells / Q000276:immunology; D020803:Encephalitis, Herpes Simplex / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000821:virology; D005799:Genes, Dominant; D018259:Herpesvirus 1, Human / Q000502:physiology; D006579:Heterozygote; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D007372:Interferons / Q000096:biosynthesis; D015603:Keratinocytes / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D009154:Mutation; D011070:Poly I-C / Q000494:pharmacology; D051196:Toll-Like Receptor 3 / Q000737:chemistry / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
chemical_list: C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D007372:Interferons; D011070:Poly I-C