Cytokine-mediated regulation of toll-like receptor expression in eosinophils

Abstract

Rationale The link between infection and exacerbation of allergic diseases may consist of various pathways, but direct activation of eosinophils by microbe-derived molecules potentially represents an explanation of such mechanisms. Although TLRs have been identified as functionally important receptors for recognition of pathogens, the precise expression profiles and functions of TLRs in eosinophils have remained largely unclear. Methods We quantified the expression levels of TLR mRNA in eosinophils by real-time PCR and studied the functional properties of eosinophil TLRs. We also examined the modulation of eosinophil TLR expression by cytokines. Results Eosinophils constitutively expressed TLR1, TLR4, TLR7, TLR9 and TLR10 mRNAs. Among various TLR ligands, only R-848, a ligand of TLR7 and TLR8, regulated CD11b and L-selectin expression, prolonged survival and induced superoxide generation in eosinophils. Stimulation of eosinophils by R-848 led to p38 MAPK activation and a p38 MAPK inhibitor almost completely attenuated R-848-induced superoxide generation. Although TLR8 mRNA expression was hardly detectable in freshly isolated eosinophils, mRNA expression of TLR8 as well as TLR7 was exclusively up-regulated by IFN-g but not by either IL-4 or IL-5. The up-regulation of the TLRs by IFN-g had potentially functional significance: the extent of R-848-induced modulation of adhesion molecule expression was significantly greater in cells treated with IFN-g compared with untreated cells. Conclusions Although the natural ligands for TLR7 and TLR8 have not yet been identified, our results suggest that eosinophil TLR7/8 systems represent a potentially important mechanism of a host-defensive role against viral infection and mechanism linking exacerbation of allergic inflammation and viral infection.