Rhinovirus infection enhances Th2-type allergic airways disease associated production of mucus and IgE
Session IV – Bartlett, Nathan
Title of Contribution: Rhinovirus infection enhances Th2-type allergic airways disease associated production of mucus and IgE
Author(s): Nathan W. Bartlett, Ross P. Walton, Gary R. Mclean, Simon D. Message and Sebastian L. Johnston
Affiliation(s): Imperial College London
Abstract:
Rhinovirus (RV) infection appears to be the dominant individual cause of acute exacerbations in both adults and children. Despite the enormous associated morbidity the mechanisms of RV induced asthma exacerbations are poorly understood. Numerous studies have shown that cytokines expressed by Th2 cells regulate disease processes commonly associated with allergic asthma such as and mucus hyper-secretion and IgE production. Whilst there is substantial evidence that Th2-type immune responses are important drivers in rhinovirus-induced asthma exacerbations, we know very little about how RV infections influence allergen-specific Th2 responses to cause an asthma attack. The MUC5AC and MUC5B proteins are major components of secreted respiratory mucus which can form plugs that occlude airways during asthma attacks. In a human study atopic asthmatic and non-asthmatic subjects were experimentally infected with RV and MUC5B protein in BAL fluid was measured at baseline and day 4. At baseline MUC5B protein was significantly increased (P<0.05) in asthmatic BAL compared to non-asthmatic subjects. At day 4 after infection BAL from normal subjects contained significantly increased (3 fold, P<0.01) levels of MUC5B. Interestingly MUC5B protein in asthmatic BAL, although higher than normal at baseline, did not appear further increased following RV infection. In mice we have developed a RV-induced asthma exacerbation model in which Th2 polarized, OVA-specific DO11.10 CD4+ lymphocytes were transferred to naïve congenic Balb/c mice. Mice were then challenged intransally with OVA and/or infected with RV. At day 6 we observed significantly increased MUC5AC and MUC5B protein in BAL from the RV infected/OVA treated mice. In these mice we also observed 3 fold increased (P<0.05) OVA-specific serum IgE compared to uninfected OVA treated mice. A clear Th2 skewing of OVA-specific serum IgG responses was evident with significant levels of IgG1 (but no IgG2a) detected in RV-OVA and OVA-only treated mice. However, unlike IgE, RV infection did not increase OVA-specific IgG1 levels over that observed in uninfected mice dosed with OVA. OVA-specific IgE, IgG1 or IgG2a were undetectable in serum from mice that were not intranasally dosed with OVA indicating that RV infection, in the absence of allergen in the airways, is not sufficient to induce allergen-specific serum antibodies despite the presence of transferred allergen specific Th2 cells. These studies provide evidence that RV infection can augment important pathogenic mechanisms in asthma (mucus production and allergen specific-IgE), demonstrating the potential benefit of anti-rhinoviral therapy to treat asthma exacerbations.
