Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease that develops following repeated exposure to inhaled environmental antigens. The disease results in alveolitis and granuloma formation and may progress to a chronic form associated with fibrosis; a greater understanding of the immunopathogenic mechanisms leading to chronic HP is needed. We used the Saccharopolyspora rectivirgula (SR) mouse model of HP to determine the extent to which a switch to a Th2-type immune response is associated with chronic HP. Exposure of wildtype (WT) and tlr2/9-/- mice to SR for 14 wk resulted in neutrophilic and lymphocytic alveolitis that was not dependent on Toll-like receptors (TLRs) 2 and 9. Long-term exposure of WT mice to SR resulted in a significant increase in collagen deposition, protein leakage, and IL-1α accompanied by a decrease in quasistatic compliance and total lung capacity compared with unexposed mice. This was associated with an increase in IL-17 but not IL-4 production or recruitment of Th2 cells. tlr2/9-/- mice exhibited an increase in protein leakage but less IL-1α and collagen deposition in the lungs compared with WT mice, yet they still displayed a decrease in quasistatic compliance, although total lung capacity was not affected. These mice exhibited an increase in both IL-13 and IL-17, which suggests that IL-13 may ameliorate some of the lung damage caused by long-term SR exposure. Our results suggest that lung pathology following long-term SR exposure in WT mice is associated with the IL-17 response and that TLRs 2 and 9 may inhibit the development of the IL-13/Th2 response.
|Journal||American Journal of Physiology - Lung Cellular and Molecular Physiology|
|State||Published - Mar 1 2016|
Bibliographical noteFunding Information:
This work was supported by National Heart, Lung, and Blood Institute Grants HL-084172 to E.A. Fitzpatrick and HL-094366 and HL-123540 to C.M. Waters.
© 2016 the American Physiological Society.
- Hypersensitivity pneumonitis
- Toll-like receptors 2 and 9
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Physiology (medical)
- Cell Biology