Influenza-derived peptides cross-react with allergens and provide asthma protection

Publication date: Available online 10 November 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Chrysanthi Skevaki, Christoph Hudemann, Mikhail Matrosovich, Christian Möbs, Sinu Paul, Andreas Wachtendorf, Bilal Alashkar Alhamwe, Daniel P. Potaczek, Stefanie Hagner, Diethard Gemsa, Holger Garn, Alessandro Sette, Harald Renz
BackgroundThe 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.ObjectiveSince little is known about the contribution of respiratory viruses in this context, we evaluated the effect of prior influenza-infection on the development of allergic asthma.MethodsMice were infected with influenza and once recovered, subjected to an ovalbumin or house dust mite-induced experimental asthma protocol. Influenza-polarized T effector memory cells (Tem) were adoptively transferred to allergen sensitized animals prior to 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.ResultsWe found in two murine models a long-lasting preventive effect against experimental asthma features. Protection could be attributed about equally to CD4+ and CD8+ T-effector memory (Tem) cells from influenza-infected mice. An in silico bioinformatic analysis identified four influenza and three allergen-derived MHC-class I and –class II candidate T-cell epitopes with potential antigen-specific cross-reactivity between influenza and allergens. Lymphocytes from influenza-infected mice produced IFNγ and IL-2 but not IL-5 upon stimulation with the aforementioned peptides. Immunization with a mixture of the influenza-peptides conferred asthma protection, and peptide immunized mice transferred protection via CD4+ and CD8+ Tem cells.ConclusionOur results illustrate for the first time heterologous immunity of virus-infected animals towards allergens. This finding extends the original hygiene hypothesis.



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