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Role of atopic status in Toll‐like receptor (TLR)7‐ and TLR9‐mediated activation of human eosinophils
Author(s) -
Månsson Anne,
Cardell LarsOlaf
Publication year - 2009
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0808494
Subject(s) - immunology , tlr9 , eosinophil , biology , tlr7 , cytokine , interleukin 5 , allergic inflammation , eosinophil cationic protein , allergy , toll like receptor , innate immune system , immune system , interleukin , gene expression , biochemistry , asthma , dna methylation , gene
Viral respiratory infections are increasingly implicated in allergic exacerbations. The mechanisms behind this are not known, but a virus‐induced activation of eosinophils through TLRs could be involved. Herein, we investigated the expression and function of TLR7 and TLR9 in purified eosinophils from peripheral blood and assessed their role in allergic airway inflammation. Eosinophils expressed TLR7 and TLR9 proteins. Stimulation with the cognate ligands R‐837 and CpG was found to prolong survival, up‐regulate expression of CD11b and conversely down‐regulate L‐selectin expression, increase expression of the activation marker CD69, facilitate the chemotactic migration, and enhance IL‐8 secretion by eosinophils. Also, CpG induced release of eosinophil‐derived neurotoxin (EDN), and R‐837 failed to do so. Analogously, eosinophils activated by CpG, but not R‐837, promoted airway epithelial cell death and cytokine release. Priming with the allergic mediators histamine, IL‐4, and most prominently IL‐5, augmented the TLR‐induced IL‐8 and EDN secretion, revealing an ability to sensitize eosinophils for TLR7 and TLR9 activation. Moreover, the TLR responses of eosinophils were higher in allergic as compared with healthy subjects, manifested by an increase in IL‐8 and EDN release. Correspondingly, allergic subjects displayed an elevated serum level of IL‐5, suggesting increased IL‐5‐mediated priming. This study shows that activation via TLR7 and TLR9 affects several eosinophil functions and that the atopic status of the donor and the presence of a Th2‐like cytokine milieu affect the outcome of the response. Thus, eosinophil activation via TLR7 and TLR9 might engender a link between viral infection and allergic exacerbations.