House dust mite allergic airway inflammation facilitates neosensitization to inhaled allergen in mice.

Background The mechanism by which many monosensitized allergic individuals progress to polysensitization over time remains to be elucidated. Mouse models have contributed greatly to the understanding of sensitization to inhaled allergens in healthy airways but hardly any studies have addressed sensitization during established allergy. We hypothesized that an allergic inflammatory milieu might facilitate sensitization to inhaled allergens by the presence of mature dendritic cells (DCs) and IL-4. Methods Mice with house dust mite (HDM)-induced allergic airway inflammation received a single intratracheal dose of ovalbumin (OVA), 2days after the last HDM exposure. Ten days later, sensitization was assessed by rechallenge with OVA. We evaluated the following factors for their importance in neosensitization: (1) maturation and recruitment of DCs to the airways, (2) dependency on DCs using CD11cDTR conditional knockout mice, (3) presence of ongoing airway inflammation by comparing sensitization at day 2 and day 14 after the last HDM exposure and (4) dependency on IL-4 by treatment with blocking antibodies. Results House dust mite -induced inflammation facilitated neosensitization to OVA. HDM-induced inflammation increased the number of airway DCs with a mature phenotype but a DC reduction of 93% did not inhibit sensitization. Neosensitization to OVA was dependent on ongoing inflammation and in particular on IL-4. Conclusions These findings show that HDM-induced allergic airway inflammation facilitates neosensitization to a second inhaled allergen in an IL-4-dependent manner and provide insight into the underlying mechanism of the frequently observed progression to polysensitization in HDM-monosensitized individuals.