Chronic hypersensitivity pneumonitis caused by saccharopolyspora rectivirgula is not associated with a switch to a Th2 response

Kelly Andrews, Manik C. Ghosh, Andreas Schwingshackl, Gabriel Rapalo, Charlean Luellen, Christopher M. Waters, Elizabeth A. Fitzpatrick

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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.

Original languageEnglish
Pages (from-to)L393-L402
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number5
StatePublished - Mar 1 2016

Bibliographical note

Funding 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.

Publisher Copyright:
© 2016 the American Physiological Society.


  • Fibrosis
  • Hypersensitivity pneumonitis
  • Toll-like receptors 2 and 9

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


Dive into the research topics of 'Chronic hypersensitivity pneumonitis caused by saccharopolyspora rectivirgula is not associated with a switch to a Th2 response'. Together they form a unique fingerprint.

Cite this