Influenza-derived peptides cross-react with allergens and provide asthma protection - 06/09/18
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Abstract |
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-γ 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.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Influenza virus, asthma, hygiene hypothesis, effector memory cells, heterologous immunity
Abbreviations used : BAL, BLAST, CD62L, dpi, HBV, HDM, H1N1, IEDB, IFV, NP, OVA, PA, PAS, PB, PBST, TCR, Tem
Plan
Supported by the Deutsche Forschungsgemeinschaft (DFG)–funded SFB 1021, the German Center for Lung Research (DZL; 82DZL00502/A2), and the German Academic Exchange Service (DAAD; B.A.A., personal reference number: 91559386). |
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Disclosure of potential conflict of interest: C. Skevaki has received grants from the German Research Foundation (DFG), the German Center for Lung Research (DZL), and the European Union FP7 PREDICTA, and has received payment for research projects from Hycor and Mead Johnson Nutritional and has received consultation fees from Hycor and Bencard. M. Matrosovich has received a grant from the German Research Foundation. H. Renz has received a grant from the German Research Foundation and payment for lectures from Allergopharma, Novartis, Thermo Fisher, Danone, Mead Johnson Nutritional, and Bencard and has received payment for research and development projects from Hycor, Mead Johnson, and Beckman Coulter. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 142 - N° 3
P. 804-814 - septembre 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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