BACKGROUND: The hygiene hypothesis is the leading concept to explain the current asthma epidemic, which is built on the observation that a lack of bacterial contact early in life induces allergic TH2 immune responses. OBJECTIVE: Because little is known about the contribution of respiratory tract viruses in this context, we evaluated the effect of prior influenza infection on the development of allergic asthma. METHODS: Mice were infected with influenza and, once recovered, subjected to an ovalbumin- or house dust mite-induced experimental asthma protocol. Influenza-polarized effector memory T (Tem) cells were transferred adoptively to allergen-sensitized animals before allergen challenge. A comprehensive in silico analysis assessed homologies between virus- and allergen-derived proteins. Influenza-polarized Tem cells were stimulated ex vivo with candidate peptides. Mice were immunized with a pool of virus-derived T-cell epitopes. RESULTS: In 2 murine models we found a long-lasting preventive effect against experimental asthma features. Protection could be attributed about equally to CD4(+) and CD8(+) Tem cells from influenza-infected mice. An in silico bioinformatic analysis identified 4 influenza- and 3 allergen-derived MHC class I and MHC class II candidate T-cell epitopes with potential antigen-specific cross-reactivity between influenza and allergens. Lymphocytes from influenza-infected mice produced IFN-gamma and IL-2 but not IL-5 on stimulation with the aforementioned peptides. Immunization with a mixture of the influenza peptides conferred asthma protection, and peptide-immunized mice transferred protection through CD4(+) and CD8(+) Tem cells. CONCLUSION: For the first time, our results illustrate heterologous immunity of virus-infected animals toward allergens. This finding extends the original hygiene hypothesis.
- Skevaki, C.
- Hudemann, C.
- Matrosovich, M.
- Mobs, C.
- Paul, S.
- Wachtendorf, A.
- Alashkar Alhamwe, B.
- Potaczek, D. P.
- Hagner, S.
- Gemsa, D.
- Garn, H.
- Sette, A.
- Renz, H.
Keywords
- Influenza virus
- asthma
- effector memory cells
- heterologous immunity
- hygiene hypothesis
