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: 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 Barreiro, Joshua 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
• Journal: Science (New York, N.Y.) (Science) Vol. 317 Issue 5844 Pg. 1522-7 (Sep 14 2007) ISSN: 1095-9203 [Electronic] United States
• PMID: 17872438 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• TLR3 protein, human
• Toll-Like Receptor 3
• Interferons
• Poly I-C

Topics

• 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)