The innate immune facet of brain: human neurons express TLR-3 and sense viral dsRNA.
Inflammation is an important factor in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease or multiple sclerosis, and during microbial infections of the nervous system. Glial cells were thought to be the main contributor for cytokine and chemokine production and Toll-like receptor (TLR) expression in the brain. Here, we report that human neurons express TLR-3, a major receptor in virus-mediated innate immune response. We established that these cells can mount a strong inflammatory response characterized by the expression of inflammatory cytokines (TNF-alpha, IL-6), chemokines (CCL-5 and CXCL-10), and antiviral molecules (2'5'OAS and IFN-beta) after treatment with dsRNA - a by-product of viral infection and ligand of TLR-3. This work firmly establishes that human neurons, in absence of glia, have the intrinsic machinery to trigger robust inflammatory, chemoattractive, and antiviral responses.
Lafon
Monique
M
Unité de Neuroimmunologie Virale, Department of Neuroscience, Institut Pasteur, 75724 Paris, France. mlafon@pasteur.fr
Megret
Françoise
F
Lafage
Mireille
M
Prehaud
Christophe
C
D001921:Brain / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000276:immunology; D007370:Interferon Type I / Q000494:pharmacology; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000276:immunology / Q000378:metabolism*; D009928:Organ Specificity; D011070:Poly I-C / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051194:Toll-Like Receptor 1 / Q000235:genetics; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051196:Toll-Like Receptor 3 / Q000096:biosynthesis* / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D014777:Virus Diseases / Q000276:immunology
D018925:Chemokines; D016207:Cytokines; D007370:Interferon Type I; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D011994:Recombinant Proteins; C495342:TLR2 protein, human; C495344:TLR3 protein, human; C495345:TLR4 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D016899:Interferon-beta; D011070:Poly I-C