TLR3 deficiency in patients with herpes simplex encephalitis

Shen Ying Zhang, Emmanuelle Jouanguy, Sophie Ugolini, Asma Smahi, Gaëlle Elain, Pedro Romero, David Segal, Vanessa Sancho-Shimizu, Lazaro Lorenzo, Anne Puel, Capucine Picard, Ariane Chapgier, Sabine Plancoulaine, Matthias Titeux, Céline Cognet, Horst Von Bernuth, Cheng Lung Ku, Armanda Casrouge, Xin Xin Zhang, Luis BarreiroJoshua Leonard, Claire Hamilton, Pierre Lebon, Bénédicte Héron, Louis Vallée, Lluis Quintana-Murci, Alain Hovnanian, Flore Rozenberg, Eric Vivier, Frédéric Geissmann, Marc Tardieu, Laurent Abel, Jean Laurent Casanova*

*Corresponding author for this work

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1522-1527
Number of pages6
JournalScience
Volume317
Issue number5844
DOIs
StatePublished - Sep 14 2007

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Cite this

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., ... Casanova, J. L. (2007). TLR3 deficiency in patients with herpes simplex encephalitis. Science, 317(5844), 1522-1527. https://doi.org/10.1126/science.1139522