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Suppression of dust mite allergy by mucosal delivery of a hypoallergenic derivative in a mouse model

  • Applied genetics and molecular biotechnology
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Abstract

Allergic asthma caused by house dust mite (HDM) is becoming a public health problem. Specific immunotherapy is considered to be the only curative treatment, but it is always associated with IgE-mediated side effects in the therapy process. A few studies showed that the disruption of allergen IgE epitopes could reduce IgE reactivity and thus reduce allergenic activity. In this study, a hypoallergenic derivative of the major HDM allergen Der p2 was constructed by genetic engineering. This derivative was confirmed to have a considerably reduced IgE reactivity compared with Der p2. For its application in vivo, recombinant Lactococcus lactis (LL-DM) was engineered to deliver the Der p2 derivative to the intestinal mucosal surface. Oral administration of LL-DM significantly alleviated Der p2-induced airway inflammation, as shown by reduced inflammatory infiltration and a reduction in Th2 cytokines in bronchoalveolar lavage. This protective effect was associated with an up-regulation of specific IgG2a and a decrease in IL-4 level in the spleen which may affect specific IgE response. Moreover, the levels of regulatory T cells in the mesenteric lymph nodes and spleen were markedly increased in mice fed with LL-DM, suggesting that LL-DM can inhibit allergic responses via the induction of regulatory T cell. Our results indicate that the Der p2 derivative is a promising therapeutic molecule for specific immunotherapy and recombinant lactic acid bacteria could be developed as a promising treatment or prevention strategy for allergic diseases.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 31200691), the National Science and Technology Pillar Program (2013BAD18B01), the 111 project B07029, IRT124, and the Priority Academic Program Development of Jiangsu Higher Education Institutions.

Conflict of interest

All authors declared that they have no conflict of interest.

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Authors and Affiliations

  1. State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi, 214122, People’s Republic of China

    Chunqing Ai, Qiuxiang Zhang, Junrong Ding, Chengcheng Ren, Gang Wang, Xiaoming Liu, Fengwei Tian, Jianxin Zhao, Hao Zhang, Yong Q. Chen & Wei Chen

  2. Synergistic Innovation Center for Food Safety and Nutrition, Wuxi, 214122, People’s Republic of China

    Yong Q. Chen & Wei Chen

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  1. Chunqing Ai
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  2. Qiuxiang Zhang
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  4. Chengcheng Ren
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  5. Gang Wang
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  6. Xiaoming Liu
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  7. Fengwei Tian
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  8. Jianxin Zhao
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  9. Hao Zhang
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  10. Yong Q. Chen
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  11. Wei Chen
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Correspondence to Qiuxiang Zhang or Wei Chen.

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Ai, C., Zhang, Q., Ding, J. et al. Suppression of dust mite allergy by mucosal delivery of a hypoallergenic derivative in a mouse model. Appl Microbiol Biotechnol 99, 4309–4319 (2015). https://doi.org/10.1007/s00253-015-6407-6

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  • DOI: https://doi.org/10.1007/s00253-015-6407-6

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