Adenoviral infection inhibits allergic airways inflammation in mice

Background Recent epidemiological studies have suggested that exposure to c ertain viruses and bacteria influences the development of allergy and aller gic diseases, such as asthma. However, there is a paucity of experimental e vidence examining the consequences of concurrent exposure to allergen and i nfectious agents, and the potential mechanisms by which allergic disease mi ght be averted as a result. Objective To model this situation experimentally, we investigated whether a virally induced immune response, elicited by a replication-deficient human type 5 adenovirus (RDA) administered at a site distant from the airways, c ould inhibit ovalbumin (OVA)-induced airways eosinophilic inflammation. Methods C57BL/6 mice were infected intramuscularly with RDA 16 h prior to i ntraperitoneal OVA sensitization. Cellular and cytokine responses in the lu ng/airways were examined after an OVA aerosol challenge. Results RDA infection significantly inhibited the inflammatory response in the lung tissue after antigen challenge. In the bronchoalveolar lavage (BAL ), total cell number, eosinophils and lymphocytes were decreased by 70, 85 and 65%, respectively, after antigen challenge in RDA-treated, compared wit h untreated, mice. RDA infection had no effect on IgE synthesis. The levels of IL-5, IL-4 and IFN gamma in the BAL after antigen challenge were signif icantly lower in RDA-treated mice. In vitro production of cytokines by sple nocytes in response to OVA restimulation revealed a shift from IL-4 in sens itized, PBS-treated mice, to IFN gamma in sensitized mice treated with RDA. Flow cytometric analysis revealed that RDA infection increased the proport ion of CD8 T cells in the BAL; this change in T-cell subsets was accompanie d by an increase in both CD4 and CD8 T cells positive for intracellular IFN gamma. Inhibition of antigen-induced airways inflammation was IFN gamma-de pendent but did not require IL-12, as RDA-treatment inhibited airways infla mmation in IL-12 but not IFN gamma knock-out mice. Conclusion This study demonstrates that an immune response against a replic ation-deficient adenovirus during the initial exposure to OVA inhibits the development of airways inflammation after antigen aerosol challenge.