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Mycobacterial hypersensitivity pneumonitis requires TLR9–MyD88 in lung CD11b+CD11c+ cells

H. Daito, T. Kikuchi, T. Sakakibara, K. Gomi, T. Damayanti, J. Zaini, N. Tode, M. Kanehira, S. Koyama, S. Fujimura, M. Ebina, K.J. Ishii, S. Akira, T. Takai, A. Watanabe, T. Nukiwa
European Respiratory Journal 2011; DOI: 10.1183/09031936.00177110
H. Daito
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T. Kikuchi
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T. Sakakibara
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K. Gomi
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T. Damayanti
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J. Zaini
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N. Tode
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M. Kanehira
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S. Koyama
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S. Fujimura
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M. Ebina
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K.J. Ishii
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S. Akira
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T. Takai
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A. Watanabe
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T. Nukiwa
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Abstract

Mycobacteria are among the most common causes of hypersensitivity pneumonitis (HP), but controversy persists with regard to involvement of the infectious potency in mycobacterial HP (hot tub lung). This study aimed to establish a mouse model of hot tub lung to clarify its pathophysiology.

Mice were exposed intranasally to formalin-killed Mycobacterium avium from a patient with hot tub lung (HP strain) or chronic pulmonary infection (non-HP strain), and bronchoalveolar lavage fluids and lung tissues were evaluated for the allergic inflammation.

Dead M. avium HP strain, but not non-HP strain, elicited marked HP-like pulmonary inflammation in wild-type mice. Although the inflammation was induced in mice lacking CD4 or CD8, the induction of HP-like responses was prevented in mice lacking MyD88 or TLR9. Cultured lung CD11c+ cells responded to M. avium in a TLR9-dependent manner, and reconstitution of TLR9−/− mice with lung CD11c+ cells from wild-type mice restored the inflammatory responses. Further investigation revealed that pulmonary exposure to M. avium HP strain increased the number of lung CD11b+CD11c+ cells (dendritic cells) through the TLR9 triggering.

Our results provide evidence that hot tub lung develops via the mycobacterial engagement of the TLR9–MyD88 signaling in lung CD11b+ dendritic cells without the infectious capacity.

  • Dendritic cells
  • hypersensitivity pneumonitis
  • non-tuberculous mycobacteria
  • Toll-like receptors and innate immunity
  • ERS
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Mycobacterial hypersensitivity pneumonitis requires TLR9–MyD88 in lung CD11b+CD11c+ cells
H. Daito, T. Kikuchi, T. Sakakibara, K. Gomi, T. Damayanti, J. Zaini, N. Tode, M. Kanehira, S. Koyama, S. Fujimura, M. Ebina, K.J. Ishii, S. Akira, T. Takai, A. Watanabe, T. Nukiwa
European Respiratory Journal Jan 2011, erj01771-2010; DOI: 10.1183/09031936.00177110

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Mycobacterial hypersensitivity pneumonitis requires TLR9–MyD88 in lung CD11b+CD11c+ cells
H. Daito, T. Kikuchi, T. Sakakibara, K. Gomi, T. Damayanti, J. Zaini, N. Tode, M. Kanehira, S. Koyama, S. Fujimura, M. Ebina, K.J. Ishii, S. Akira, T. Takai, A. Watanabe, T. Nukiwa
European Respiratory Journal Jan 2011, erj01771-2010; DOI: 10.1183/09031936.00177110
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