title: The expression of Toll-like receptor 4, 7 and co-receptors in neurochemical sub-populations of rat trigeminal ganglion sensory neurons.
abstract: The recent discovery that mammalian nociceptors express Toll-like receptors (TLRs) has raised the possibility that these cells directly detect and respond to pathogens with implications for either direct nociceptor activation or sensitization. A range of neuronal TLRs have been identified, however a detailed description regarding the distribution of expression of these receptors within sub-populations of sensory neurons is lacking. There is also some debate as to the composition of the TLR4 receptor complex on sensory neurons. Here we use a range of techniques to quantify the expression of TLR4, TLR7 and some associated molecules within neurochemically-identified sub-populations of trigeminal (TG) and dorsal root (DRG) ganglion sensory neurons. We also detail the pattern of expression and co-expression of two isoforms of lysophosphatidylcholine acyltransferase (LPCAT), a phospholipid remodeling enzyme previously shown to be involved in the lipopolysaccharide-dependent TLR4 response in monocytes, within sensory ganglia. Immunohistochemistry shows that both TLR4 and TLR7 preferentially co-localize with transient receptor potential vallinoid 1 (TRPV1) and purinergic receptor P2X ligand-gated ion channel 3 (P2X3), markers of nociceptor populations, within both TG and DRG. A gene expression profile shows that TG sensory neurons express a range of TLR-associated molecules. LPCAT1 is expressed by a proportion of both nociceptors and non-nociceptive neurons. LPCAT2 immunostaining is absent from neuronal profiles within both TG and DRG and is confined to non-neuronal cell types under naïve conditions. Together, our results show that nociceptors express the molecular machinery required to directly respond to pathogenic challenge independently from the innate immune system.
authors.affiliation: School of Dentistry, Plymouth University Peninsula Schools of Medicine & Dentistry, Plymouth University, Plymouth, Devon PL4 8AA, UK.
authors.forename: M P
authors.initials: MP
authors.lastname: Helley
authors.affiliation: School of Biomedical & Healthcare Science, Plymouth University Peninsula Schools of Medicine & Dentistry, Plymouth University, Plymouth, Devon PL4 8AA, UK.
authors.forename: W
authors.initials: W
authors.lastname: Abate
authors.affiliation: School of Biomedical & Healthcare Science, Plymouth University Peninsula Schools of Medicine & Dentistry, Plymouth University, Plymouth, Devon PL4 8AA, UK.
authors.forename: S K
authors.initials: SK
authors.lastname: Jackson
authors.affiliation: School of Dentistry, Plymouth University Peninsula Schools of Medicine & Dentistry, Plymouth University, Plymouth, Devon PL4 8AA, UK.
authors.forename: J H
authors.initials: JH
authors.lastname: Bennett
authors.affiliation: School of Biomedical & Healthcare Science, Plymouth University Peninsula Schools of Medicine & Dentistry, Plymouth University, Plymouth, Devon PL4 8AA, UK. Electronic address: stephen.thompson@plymouth.ac.uk.
authors.forename: S W N
authors.initials: SW
authors.lastname: Thompson
mesh_terms: D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000378:metabolism; D000818:Animals; D005727:Ganglia, Spinal / Q000378:metabolism*; D008297:Male; D009619:Nociceptors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D051199:Toll-Like Receptor 7 / Q000378:metabolism*; D012668:Trigeminal Ganglion / Q000378:metabolism*
chemical_list: D051197:Toll-Like Receptor 4; D051199:Toll-Like Receptor 7; D008243:1-Acylglycerophosphocholine O-Acyltransferase
keywords: Toll-like receptor; cell signaling; dorsal root ganglion; pain; sensory neuron; trigeminal ganglion