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Inflammation Research

, Volume 65, Issue 3, pp 235–244 | Cite as

A critical role of Dectin-1 in hypersensitivity pneumonitis

  • Mari Higashino-Kameda
  • Toshiki Yabe-Wada
  • Shintaro Matsuba
  • Kazuya Takeda
  • Kazushi Anzawa
  • Takashi Mochizuki
  • Koichi Makimura
  • Shinobu Saijo
  • Yoichiro Iwakura
  • Hirohisa Toga
  • Akira Nakamura
Original Research Paper

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.

Keywords

Dectin-1 Hypersensitivity pneumonitis Th17 Trichosporon asahii 

Notes

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.).

Compliance with ethical standards

Conflict of interest

The authors have no financial conflict of interest.

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Copyright information

© Springer International Publishing 2015

Authors and Affiliations

  • Mari Higashino-Kameda
    • 1
    • 2
  • Toshiki Yabe-Wada
    • 2
  • Shintaro Matsuba
    • 2
  • Kazuya Takeda
    • 2
  • Kazushi Anzawa
    • 3
  • Takashi Mochizuki
    • 3
  • Koichi Makimura
    • 4
  • Shinobu Saijo
    • 5
  • Yoichiro Iwakura
    • 6
  • Hirohisa Toga
    • 1
  • Akira Nakamura
    • 2
  1. 1.Department of Respiratory MedicineKanazawa Medical UniversityUchinadaJapan
  2. 2.Department of ImmunologyKanazawa Medical UniversityUchinadaJapan
  3. 3.Department of DermatologyKanazawa Medical UniversityUchinadaJapan
  4. 4.Laboratory of Space and Environmental MedicineTeikyo UniversityHachiojiJapan
  5. 5.Division of Molecular Immunology, Medical Mycology Research CenterChiba UniversityChibaJapan
  6. 6.Center for Animal Disease Models, Research Institute for Biological SciencesTokyo University of ScienceNodaJapan

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