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 T_H2 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.

中文翻译：

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流感衍生肽与过敏原交叉反应并提供哮喘保护

背景

卫生假说是解释当前哮喘流行的主要概念，该观点建立在观察到生命早期缺乏细菌接触会引起过敏性T _H 2免疫反应的基础上。

客观的

由于在这种情况下对呼吸道病毒的贡献知之甚少，因此我们评估了先前的流感感染对过敏性哮喘发展的影响。

方法

小鼠感染了流感，一旦康复，就受到卵白蛋白或屋尘螨诱导的实验性哮喘方案的感染。在过敏原激发之前，将流感极化的效应记忆T（Tem）细胞过继转移给过敏原致敏的动物。全面的计算机分析可以评估病毒和过敏原蛋白之间的同源性。用候选肽离体刺激流感极化的Tem细胞。用一组病毒衍生的T细胞表位免疫小鼠。

结果

在2种小鼠模型中，我们发现了针对实验性哮喘特征的长期预防作用。保护作用可以大致等同于来自流感感染小鼠的CD4 ⁺和CD8 ⁺ Tem细胞。一个在硅片的生物信息学分析鉴定4流行性感冒和3的变应原衍生的MHC I类和MHC II类候选T细胞表位与流感和过敏原之间的潜在抗原特异的交叉反应性。来自流感感染的小鼠的淋巴细胞经上述肽刺激后产生IFN-γ和IL-2，但不产生IL-5。混合流感肽可预防哮喘，肽免疫小鼠可通过CD4 ⁺和CD8 ⁺ Tem细胞转移保护。

结论

我们的结果首次说明了病毒感染的动物对变应原的异源免疫。这一发现扩展了原始的卫生假说。