Toll-like receptor 2-independent and MyD88-dependent gene expression in the mouse brain.
Toll-like receptors (TLRs) are essential to mount a rapid innate immune reaction to pathogens. Although TLR2 is the key receptor for pathogen-associated molecular patterns from Gram-positive bacteria, a robust transcriptional activation of the gene encoding this receptor takes place in the brain of mice exposed to the TLR4 ligand lipopolysaccharide (LPS). TLR2 gene expression is actually used as a reliable marker of activated microglia in vivo, but its functions remain unknown. The present study investigated the role of this receptor in mediating LPS-induced gene expression in the mouse brain. Immune genes were measured using both in situ hybridization and real time RT-PCR. Despite the robust microglial TLR2 expression, this receptor does not modulate transcriptional activity by TLR4 signaling. TLR2-deficient mice and their wild-type littermates had similar IkappaBalpha mRNA levels and induction of innate immune genes from 6 h to 10 days after LPS injection. In contrast, NF-kappaB activity, cytokine, chemokine, TLR2 and CD14 transcripts were no longer detected in MyD88-deficient mice. Indeed, the hybridization signal for most of the transcripts measured in this study was similar in the brain of MyD88(-/-) mice exposed to either saline or LPS. These data indicate that while TLR2 transcription is dependent on MyD88 signaling in microglia, this innate immune receptor is not involved in the immune response to LPS. On the other hand, MyD88 pathway is essential for the endotoxin to induce expression of immune genes in the central nervous system.
Naert
Gaëlle
G
Laboratory of Molecular Endocrinology, CHUL Research Center and Department of Anatomy and Physiology, Laval University, Québec, Québec, Canada.
Laflamme
Nathalie
N
Rivest
Serge
S
D000818:Animals; D001921:Brain / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*
D016207:Cytokines; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2