Honey Bee (Apis mellifera) Venom Induces AIM2 Inflammasome Activation in Human Keratinocytes

Allergy, 2012 Sep 13BACKGROUND:Following allergen exposure, cytokines and otherpro-inflammatory signals play an important role in the immunological cascadeleading to allergic sensitization. Inflammasomes sense exogenous and endogenousdanger signals and trigger IL-1β and IL-18 activation which in turn shape Th2responses. Honey bee venom (BV) allergies are very common; however, the localinflammatory cascade leading to the initiation of allergic sensitization ispoorly understood. In this study, the local inflammatory cascades in skin afterexposure to BV were investigated.METHODS:The mechanisms of inflammasome activation in human skin andin cultured keratinocytes upon BV exposure were analyzed by ELISA, Westernblot, flow cytometry, siRNA techniques, and immunofluorescence.RESULTS:In an ex vivo bee sting model, BV induced IL-1β releasesuggesting the activation of inflammasomes. Indeed, in cultured keratinocytes,the BV component melittin triggered IL-1β and IL-18 release via the AIM2inflammasome. AIM2 is a cytosolic DNA receptor, and mitochondrial as well asgenomic DNA was detected in the cytosol of melittin-treated keratinocytes astriggers of inflammasome activation. As a mechanism, melittin mediateddestruction of mitochondrial membranes leading to the leakage of mitochondrial DNAinto the cytosolic compartment.CONCLUSION:These data suggest that upon BV exposure, keratinocytes areinvolved in an innate immune response by the activation of the AIM2inflammasome and subsequent IL-1β and IL-18 release triggered by endogenous DNA.As IL-1β and IL-18 are involved in Th2- and IgE-mediated immune reactions,these results could add to the understanding of the role of the tissuemicroenvironment to subsequent allergic responses.