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Role of atopic status in Toll-like receptor (TLR)7- and TLR9-mediated activation of human eosinophils.

Journal of leukocyte biology (2009-01-09)
Anne Månsson, Lars-Olaf Cardell
ABSTRACT

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.

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Atto 488 NHS ester, BioReagent, suitable for fluorescence, ≥80% (coupling to amines)
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Atto 488, suitable for fluorescence, ≥90% (HPCE)
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Atto 488-Biotin, BioReagent, suitable for fluorescence, ~75% (HPCE)
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Atto 488 maleimide, BioReagent, suitable for fluorescence, ≥90% (coupling to thiols)
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Atto 488 amine
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Atto 488 azide
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Atto 488 iodoacetamide

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