Science：一个出乎意料的选择性免疫受体
生物谷报道：究人员报告说，免疫细胞受体TLR3的一个变异能使个体易感单纯疱疹I型病毒脑炎，但看来对免疫系统没有其他影响。这个TLR家族的受体过去被认为在抗病毒免疫中起广泛的作用，但是Shen-YingZhang和同事发现，TLR3看来只致力于保护身体不受一个具体病毒的感染，对其他病原体没有明显影响。这个发现提出，单纯疱疹I型病毒在TLR3受体进化上起过作用，该病毒能在儿童中通过口鼻传播到中枢神经系统引起脑炎。（科学时报）
原始出处：
Science 14 September 2007:
Vol. 317. no. 5844, pp. 1522 - 1527
DOI: 10.1126/science.1139522
TLR3 Deficiency in Patients with Herpes Simplex Encephalitis
Shen-Ying Zhang,1,2,3 Emmanuelle Jouanguy,1,2,3 Sophie Ugolini,4 Asma Smahi,5 Gaëlle Elain,6 Pedro Romero,7 David Segal,8 Vanessa Sancho-Shimizu,1,2 Lazaro Lorenzo,1,2 Anne Puel,1,2 Capucine Picard,1,2,9 Ariane Chapgier,1,2 Sabine Plancoulaine,1,2 Matthias Titeux,10 Céline Cognet,4 Horst von Bernuth,1,2 Cheng-Lung Ku,1,2 Armanda Casrouge,1,2 Xin-Xin Zhang,3 Luis Barreiro,11 Joshua Leonard,8 Claire Hamilton,1,2 Pierre Lebon,12 Bénédicte Héron,13 Louis Vallée,14 Lluis Quintana-Murci,11 Alain Hovnanian,10 Flore Rozenberg,12 Eric Vivier,4 Frédéric Geissmann,6 Marc Tardieu,15 Laurent Abel,1,2 Jean-Laurent Casanova1,2,3,16*
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.
1 Human Genetics of Infectious Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM), U550, Faculty Necker, Paris 75015, France.
2 University Paris René Descartes, Paris 75015, France.
3 French-Chinese Laboratory of Genetics and Life Sciences, Rui Jin Hospital, Shanghai Jiao Tong University, Shanghai 200025, China.
4 Marseille-Luminy Immunology Institute, Marseille 13288, France.
5 Department of Genetics, INSERM, U781, Necker Hospital, Paris 75015, France.
6 Laboratory of Mononuclear Cell Biology, INSERM, U838, Necker Hospital, Paris 75015, France.
7 Ludwig Institute for Cancer Research, Lausanne Branch, University Hospital, Lausanne 1005, Switzerland.
8 Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
9 Center for the Study of Immunodeficiencies, Necker Hospital, Paris 75015, France.
10 INSERM, U563, University Toulouse Paul Sabatier, Toulouse 31000, France.
11 Centre National de la Recherche Scientifique, URA3012, Pasteur Institute, Paris 75015, France.
12 Virology, Cochin-Saint-Vincent de Paul Hospital, University Paris René Descartes, Paris 75014, France.
13 Pediatric Neurology, Trousseau Hospital, Paris 75012, France.
14 Pediatric Neurology, University Hospital, Lille 59037, France.
15 Pediatric Neurology, Bicêtre Hospital, University Paris Sud, Kremlin-Bicêtre 94270, France.
16 Pediatric Hematology-Immunology, Necker Hospital, Paris 75015, France.
* To whom correspondence should be addressed. E-mail: casanova@necker.fr
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