TLR3 deficiency in patients with herpes simplex encephalitis.
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.
Zhang
Shen-Ying
SY
Human Genetics of Infectious Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM), U550, Faculty Necker, Paris 75015, France.
Jouanguy
Emmanuelle
E
Ugolini
Sophie
S
Smahi
Asma
A
Elain
Gaëlle
G
Romero
Pedro
P
Segal
David
D
Sancho-Shimizu
Vanessa
V
Lorenzo
Lazaro
L
Puel
Anne
A
Picard
Capucine
C
Chapgier
Ariane
A
Plancoulaine
Sabine
S
Titeux
Matthias
M
Cognet
Céline
C
von Bernuth
Horst
H
Ku
Cheng-Lung
CL
Casrouge
Armanda
A
Zhang
Xin-Xin
XX
Barreiro
Luis
L
Leonard
Joshua
J
Hamilton
Claire
C
Lebon
Pierre
P
Héron
Bénédicte
B
Vallée
Louis
L
Quintana-Murci
Lluis
L
Hovnanian
Alain
A
Rozenberg
Flore
F
Vivier
Eric
E
Geissmann
Frédéric
F
Tardieu
Marc
M
Abel
Laurent
L
Casanova
Jean-Laurent
JL
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
C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D007372:Interferons; D011070:Poly I-C