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Adenoviral infection inhibits allergic airways inflammation in mice

Authors


Jordana McMaster University, Department of Pathology, Room 4H-21, 1200 Main Street West, Hamilton, Ontario, Canada.

Abstract

Background

Recent epidemiological studies have suggested that exposure to certain viruses and bacteria influences the development of allergy and allergic diseases, such as asthma. However, there is a paucity of experimental evidence examining the consequences of concurrent exposure to allergen and infectious agents, and the potential mechanisms by which allergic disease might 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, could inhibit ovalbumin (OVA)-induced airways eosinophilic inflammation.

Methods

C57BL/6 mice were infected intramuscularly with RDA 16 h prior to intraperitoneal OVA sensitization. Cellular and cytokine responses in the lung/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 with untreated, mice. RDA infection had no effect on IgE synthesis. The levels of IL-5, IL-4 and IFNγ in the BAL after antigen challenge were significantly lower in RDA-treated mice. In vitro production of cytokines by splenocytes in response to OVA restimulation revealed a shift from IL-4 in sensitized, PBS-treated mice, to IFNγ in sensitized mice treated with RDA. Flow cytometric analysis revealed that RDA infection increased the proportion of CD8 T cells in the BAL; this change in T-cell subsets was accompanied by an increase in both CD4 and CD8 T cells positive for intracellular IFNγ. Inhibition of antigen-induced airways inflammation was IFNγ-dependent but did not require IL-12, as RDA-treatment inhibited airways inflammation in IL-12 but not IFNγ knock-out mice.

Conclusion

This study demonstrates that an immune response against a replication-deficient adenovirus during the initial exposure to OVA inhibits the development of airways inflammation after antigen aerosol challenge.

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