Modulation of dendritic cell function by cowshed dust extract

Abstract

We have shown previously that inhalation of cowshed dust extract (CDE) resulted in decreased airway reactivity, eosinophilic inflammation and sensitization in a mouse model of allergic asthma. Our data suggested down-regulation of allergic immune response rather than activation of a Th1 response towards the model allergen. However, the precise mechanism of allergy protection is not yet understood in detail. To gain deeper insight into CDE-induced immune modulation, we have analysed the effects of CDE on dendritic cell biology. Dendritic cells were generated from murine bone marrow cells (BMDC). Cells were stimulated with CDE and subsequently used to sensitize mice via the airways. Our results showed that cells were not able to prime mice for allergic immune response when they were treated with CDE 2 days before pulsing with allergen, whereas cells that were stimulated with CDE simultaneously to OVA pulsing induced a fully developed allergic immune response. Surprisingly, CDE-treated cells that were not able to prime mice for allergic immune response exhibit an activated phenotype with high expression of the co-stimulatory surface molecule CD86. Moreover, CDE-treated cells transiently produced high amounts of cytokines such as IL-10, IL-12p70 and TNF-α. Interestingly, blocking of autocrine-produced IL-10 in vitro partially restored the allergy-inducing capacity of CDE-exposed cells. Thus, we conclude that prolonged exposure to CDE reduces the allergy-inducing capacity of dendritic cells. Furthermore, we present evidence that an autocrine IL-10 dependent mechanism seems to be involved in down-regulation of dendritic cell function due to stimulation with CDE.