Abstract
BackgroundInnate immune recognition via Toll-like receptors (TLRs) on barrier cells like epithelial cells has been shown to influence the regulation of local immune responses. Here we determine expression level variations and functionality of TLRs in nasal epithelial cells from healthy donors.MethodsExpression levels of the different TLRs on primary nasal epithelial cells from healthy donors derived from inferior turbinates was determined by RT-PCR. Functionality of the TLRs was determined by stimulation with the respective ligand and evaluation of released mediators by Luminex ELISA.ResultsPrimary nasal epithelial cells express different levels of TLR1-6 and TLR9. We were unable to detect mRNA of TLR7, TLR8 and TLR10. Stimulation with Poly(I:C) resulted in a significant increased secretion of IL-4, IL-6, RANTES, IP-10, MIP-1β, VEGF, FGF, IL-1RA, IL-2R and G-CSF. Stimulation with PGN only resulted in significant increased production of IL-6, VEGF and IL-1RA. Although the expression of TLR4 and co-stimulatory molecules could be confirmed, primary nasal epithelial cells appeared to be unresponsive to stimulation with LPS. Furthermore, we observed huge individual differences in TLR agonist-induced mediator release, which did not correlate with the respective expression of TLRs.ConclusionOur data suggest that nasal epithelium seems to have developed a delicate system of discrimination and recognition of microbial patterns. Hypo-responsiveness to LPS could provide a mechanism to dampen the inflammatory response in the nasal mucosa in order to avoid a chronic inflammatory response. Individual, differential expression of TLRs on epithelial cells and functionality in terms of released mediators might be a crucial factor in explaining why some people develop allergies to common inhaled antigens, and others do not.
Highlights
Innate immune recognition via Toll-like receptors (TLRs) on barrier cells like epithelial cells has been shown to influence the regulation of local immune responses
Our experiments showed that primary nasal epithelial cells from most healthy donors express mRNA for TLR 1–6 and TLR9 and mainly respond to the TLR3 ligand Poly(I:C) and to the TLR2 and TLR5 agonists
We investigate the expression of all TLR receptors in primary nasal epithelial cells of healthy individuals and show an absence of TLR7 and TLR8 together with huge individual differences in mRNA expression level for TLR1-6 and TLR9
Summary
Innate immune recognition via Toll-like receptors (TLRs) on barrier cells like epithelial cells has been shown to influence the regulation of local immune responses. TLR2 is activated by a variety of bacterial lipoproteins, peptidoglycans (PGN), and lipoteichoic acids (LTA), by forming a heterodimer with TLR1 or TLR6 [7, 8]. TLR4 appears to form homodimers and under participation of adaptor molecules like MD-2 and CD14 this TLR recognizes lipopolysaccharide (LPS) from the outer membrane of gram-negative bacteria. Thought to be a receptor only for LPS, TLR4 emerges as a molecule responsible for signalling induced by a broad variety of molecules such as respiratory syncytial virus protein F [9], fungal components [10], or endogenous ligands like heat shock proteins, lung surfactant protein A, and beta-defensin [11,12,13]. DNA-containing CpG motifs are recognized via TLR9 [14, 15]
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