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Lactobacillus gasseri attenuates allergic airway inflammation through PPARγ activation in dendritic cells

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Abstract

Lactobacilli prevent the early development of allergic diseases in children and experimental asthma in mice. However, the detailed mechanism underlying this action remains unknown. We aimed to explore the activation pathway in the host by Lactobacillus and identify its immunomodulation mechanism in allergic asthma. Continuous administration of 107 cfu, but not 109 cfu, of L. gasseri for 4 weeks prevented Dermatophagoides pteronyssinus (Der p)-induced airway hypersensitivity and inflammation in a mouse model of allergic asthma. DNA microarray analysis of the mesenteric and lung draining lymph nodes revealed a significant decrease in inflammatory chemokines and increase in gene expression in carbohydrate and lipid metabolism, particularly of PPARγ, in 107 cfu L. gasseri-administered mice compared with untreated mice. Compared with WT mice, Der p-sensitized PPARγL/+ mice showed increased airway hyperresponsiveness to methacholine, inflammatory cell infiltration, and inflammatory cytokine secretion in bronchoalveolar fluid. Moreover, the protective effects of L. gasseri were lost in Der p-induced airway inflammation in PPARγL/+ mice, and L. gasseri-induced PPARγ activation in BMDCs inhibited the development of allergic airway inflammation in both PPARγ WT and PPARγL/+ mice. L. gasseri may act via a novel PPARγ activation pathway in DCs to alleviate allergen-induced airway inflammation in allergic asthma.

Key messages

  • L. gasseri prevents mite allergen (Der p)-induced airway inflammation.

  • Prevention of airway inflammation occurs via activation of PPARγ in dendritic cells.

  • L. gasseri administration does not reverse Der p-induced airway inflammation in PPARγ(+/−) mice.

  • L. gasseri-induced PPARγ activation inhibits development of airway inflammation in WT and PPARγ(+/−) mice.

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Acknowledgements

This work was supported by Ministry of Science and Technology (MOST) of Taiwan and research grants 99RC07, 101CB02, 102CB03, and 103CB01 from South Taiwan Science Park, MOST. The authors thank Dr. Yau-Sheng Tsai, Institute of Clinical Medicine, College of Medicine, National Chen Kung University, for providing PPARγ mice. We acknowledge Wallace Academic Editing for English proofreading.

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Authors and Affiliations

  1. Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Miao-Hsi Hsieh & Pei-Chi Chen

  2. Department of Pediatrics, Chi-Mei Medical Center, Liou-Yin, Tainan, Taiwan

    Ren-Long Jan & Jiu-Yao Wang

  3. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan

    Ren-Long Jan

  4. Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan

    Lawrence Shih-Hsin Wu

  5. Center for Allergy and Clinical Immunology Research (ACIR), College of Medicine, National Cheng Kung University, No.1 University Road, Tainan, 70428, Taiwan

    Pei-Chi Chen, Hui-Fang Kao, Wen-Shuo Kuo & Jiu-Yao Wang

  6. Department of Nursing, National Tainan Junior College of Nursing, Tainan, Taiwan

    Hui-Fang Kao

  7. Graduate Institute of Integrated Medicine, School of Chinese Medicine, China Medical University, Taichung, Taiwan

    Jiu-Yao Wang

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  1. Miao-Hsi Hsieh
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Correspondence to Jiu-Yao Wang.

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The animal research in this study is according to the affidavit of approval of animal use protocol National Cheng Kung University, and the Institutional Animal Care and Use Committee (IACUC) approval No is 101096.

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The authors declare that they have no competing interests.

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Hsieh, MH., Jan, RL., Wu, L.SH. et al. Lactobacillus gasseri attenuates allergic airway inflammation through PPARγ activation in dendritic cells. J Mol Med 96, 39–51 (2018). https://doi.org/10.1007/s00109-017-1598-1

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  • DOI: https://doi.org/10.1007/s00109-017-1598-1

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