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A critical role of Dectin-1 in hypersensitivity pneumonitis

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Abstract

Objectives and design

Hypersensitivity pneumonitis (HP) is a pulmonary disease caused by repeated exposure to various aspiration antigens, including bacteria and fungi. Although TLRs are known to be required for the generation of HP triggered by bacteria, the significance of fungal receptors remains unclear. The present study aimed to investigate whether Dectin-1 and Dectin-2 contribute to the development of experimental HP triggered by the fungus Trichosporon asahii (T. asahii) that causes summer-type HP.

Materials and methods

We investigated the binding between Dectin-Fc protein and T. asahii by a dot blot assay. We performed the histological and flow cytometric analysis in the HP model using Dectin-1-deficient (Dectin-1−/−) and Dectin-2−/− mice. We also investigated Th17/Th1 responses in lung cells, and measured an IL-17-promoting cytokine IL-23 from bone marrow-derived dendritic cells (BMDCs) by ELISA.

Results

Dectin-1 bound more strongly to T. asahii than Dectin-2. Dectin-1−/− mice barely developed HP, whereas both wild-type mice and Dectin-2−/− mice developed similar lung diseases. Dectin-1 deficiency decreased the infiltration of neutrophils and monocyte-derived macrophages and repressed the expansion of lung CD4+IL-17A+ cells. The production of IL-23 p19 was reduced in Dectin-1−/− BMDCs.

Conclusions

These data suggested Dectin-1 plays a critical role in the development of fungus-induced HP.

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Acknowledgments

We thank Ms. Hiromi Nakamura for technical assistance. This work was supported in part by Grant for Precursory Alumni Research (B) from Kanazawa Medical University (PR 2012-15 to M. H -K.). This work was also supported in part by a grant-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan (22590431 and 2546060 to A. N.).

Author information

Authors and Affiliations

  1. Department of Respiratory Medicine, Kanazawa Medical University, Uchinada, Ishikawa, Japan

    Mari Higashino-Kameda & Hirohisa Toga

  2. Department of Immunology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa Prefecture, 920-0293, Japan

    Mari Higashino-Kameda, Toshiki Yabe-Wada, Shintaro Matsuba, Kazuya Takeda & Akira Nakamura

  3. Department of Dermatology, Kanazawa Medical University, Uchinada, Ishikawa, Japan

    Kazushi Anzawa & Takashi Mochizuki

  4. Laboratory of Space and Environmental Medicine, Teikyo University, Hachioji, Tokyo, Japan

    Koichi Makimura

  5. Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, Japan

    Shinobu Saijo

  6. Center for Animal Disease Models, Research Institute for Biological Sciences, Tokyo University of Science, Noda, Chiba, Japan

    Yoichiro Iwakura

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  1. Mari Higashino-Kameda
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  2. Toshiki Yabe-Wada
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Correspondence to Akira Nakamura.

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Responsible Editor: Yoshiya Tanaka.

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Higashino-Kameda, M., Yabe-Wada, T., Matsuba, S. et al. A critical role of Dectin-1 in hypersensitivity pneumonitis. Inflamm. Res. 65, 235–244 (2016). https://doi.org/10.1007/s00011-015-0910-1

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  • DOI: https://doi.org/10.1007/s00011-015-0910-1

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