Dendritic Cells from Mycobacteria-Infected Mice Inhibits Established Allergic Airway Inflammatory Responses to Ragweed via IL-10– and IL-12–Secreting Mechanisms

Abstract

Previous studies have demonstrated that Mycobacterium bovis bacillus Calmette-Guerin (BCG) infection can inhibit de novo and established allergen-induced asthma-like responses. The aim of this study was to examine the role of dendritic cells (DCs) in BCG infection-mediated inhibition of established allergy to a common environmental allergen—ragweed. The results showed that adoptive transfer of DCs from BCG-infected mice (DC[BCG]), in contrast to DCs from naive mice (DC[naive]), significantly inhibited established allergic airway eosinophilia and mucus overproduction. The inhibitory effect was correlated with alterations of allergen-driven cytokine and chemokine production as well as VCAM-1 expression in the lung. Flow cytometric analysis showed higher surface expression of CD8α and costimulatory markers in DC(BCG) than in DC(naive). Moreover, DC(BCG) produced significantly higher levels of IL-10 and IL-12 and expressed higher levels of TLRs than did DC(naive). Furthermore, blockade of IL-10 or IL-12 significantly reversed the inhibitory effect of DC(BCG) on established allergic airway inflammation and Th2 cytokine responses. These findings suggest that DCs play a crucial role in infection-mediated inhibition of established allergic responses, and IL-10 and IL-12 production by these DCs may be a major mechanism for the inhibition.