TLR3 deficiency in patients with herpes simplex encephalitis.
Zhang S,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,Casrouge A,Zhang X,Barreiro L,Leonard J,Hamilton C,Lebon P,Héron B,Vallée L,Quintana-Murci L,Hovnanian A,Rozenberg F,Vivier E,Geissmann F,Tardieu M,Abel L,Casanova J
Source :
2007 Sep 18
Pmid / DOI:
17872438
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.