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TLR3 deficiency in patients with herpes simplex encephalitis
Shen-Ying Zhang1, Emmanuelle Jouanguy, Sophie Ugolini
1Human Genetics of Infectious Diseases, Institut National de la Santé et de la Recherche Médicale (INSERM), U550, Faculty Necker, Paris 75015, France.
Science (New York, N.Y.)
|September 18, 2007
Summary
A Toll-like receptor 3 (TLR3) gene variant causes herpes simplex virus 1 (HSV-1) encephalitis in children. TLR3 is crucial for controlling HSV-1 in the central nervous system, suggesting evolutionary pressure from neurotropic viruses.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- Toll and Toll-like receptors (TLRs) are known to confer immunity in experimental infections.
- Their role in host defense within natural ecosystems remains largely uncharacterized.
- Herpes simplex virus 1 (HSV-1) encephalitis is a severe neurological condition.
Purpose of the Study:
- To investigate the role of Toll-like receptor 3 (TLR3) in natural host defense against viral infections, specifically HSV-1.
- To identify genetic factors contributing to susceptibility to HSV-1 encephalitis.
Main Methods:
- Genetic analysis of children diagnosed with HSV-1 encephalitis.
- Expression analysis of TLR3 in the central nervous system (CNS) and peripheral cells.
- Assessment of TLR3-independent pathways in host defense.
Main Results:
- A dominant-negative TLR3 allele was identified in otherwise healthy children with HSV-1 encephalitis.
- TLR3 expression in the CNS is essential for controlling HSV-1 spread from the epithelium to the brain via cranial nerves.
- Epithelial and dendritic cells utilize TLR3-independent pathways for HSV-1 containment and defense against other pathogens in TLR3-deficient individuals.
Conclusions:
- Human TLR3 plays a redundant role in defense against most microbes but is vital for natural immunity against HSV-1 in the CNS.
- The critical role of TLR3 in controlling neurotropic viruses like HSV-1 may have driven its evolutionary maintenance.
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