Abstract
Mycobacteria are among the most common causes of hypersensitivity pneumonitis (HP), but controversy persists with regard to the involvement of the infectious potency of the organism 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 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 myeloid differentiation factor (MyD)88 or Toll-like receptor (TLR)9. 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 TLR9 signalling.
Our results provide evidence that hot tub lung develops via the mycobacterial engagement of TLR9–MyD88 signalling in lung CD11b+ dendritic cells independent of the mycobacterial infectious capacity.
- Dendritic cells
- hypersensitivity pneumonitis
- innate immunity
- nontuberculous mycobacteria
- Toll-like receptors
Footnotes
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Support Statement
These studies were supported, in part, by the Ministry of Education, Culture, Sports, Science, and Technology (Tokyo, Japan), the Core Research for Evolutional Science and Technology Program of the Japan Science and Technology Agency (Tokyo, Japan), and the Adaptable and Seamless Technology Transfer Program of the Japan Science and Technology Agency (Tokyo, Japan).
Statement of Interest
None declared.
- Received November 16, 2010.
- Accepted January 6, 2011.
- ©ERS 2011