生物谷報道：究人員報告說,，免疫細胞受體TLR3的一個變異能使個體易感單純皰疹I(lǐng)型病毒腦炎,，但看來對免疫系統(tǒng)沒有其他影響,。這個TLR家族的受體過去被認為在抗病毒免疫中起廣泛的作用，但是Shen-YingZhang和同事發(fā)現(xiàn),，TLR3看來只致力于保護身體不受一個具體病毒的感染,，對其他病原體沒有明顯影響。這個發(fā)現(xiàn)提出,，單純皰疹I(lǐng)型病毒在TLR3受體進化上起過作用,，該病毒能在兒童中通過口鼻傳播到中樞神經(jīng)系統(tǒng)引起腦炎。（科學(xué)時報）
原始出處：
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: [email protected]
