Allergic lung inflammation decreases the anti-viral response to vaccinia virus (175.3)

Abstract

Abstract Despite the global eradication of smallpox following widespread vaccination with vaccinia virus (VV), other members of the poxviridae family persist and continue to infect animal and human hosts. Although the lung is the most lethal route of poxvirus infection, there is little known about the local immune response to pulmonary VV infection. Moreover, VV vaccination is contraindicated in patients with atopic dermatitis as the pro-allergic milieu diminishes anti-VV responses. Our goal was to determine the role of allergic airway disease (AAD) on the local immune response to VV infection. Our studies demonstrated increased weight loss, airway hyperreactivity, mucus gene expression, lung pathology and virus titer in mice with AAD. In contrast to observations from cells exposed to pro-allergic cytokines, expression of antimicrobial peptide genes in the lung tissue of infected mice was similar in control mice, and mice with AAD. At 4 days post infection (dpi) there was a more robust innate response in mice with AAD as evidenced by increased infiltration of lung macrophages and granulocytes. By 10 dpi, there were increased numbers of IL-10+CD8+ and IFNγ+CD8+ T cells and enhanced secretion of IL-10 and IFNγ in the bronchoalveolar lavage fluid of mice with AAD, compared to controls. Mice with AAD also had increased VV-specific IgG1 and IgM serum antibodies. These studies suggest the allergic lung microenvironment may influence the anti-viral immune response to pulmonary VV infection.