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 Waters, Elizabeth Fitzpatrick

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 (US)
Pages (from-to)L393-L402
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume310
Issue number5
DOIs
StatePublished - Mar 1 2016

Fingerprint

Saccharopolyspora
Extrinsic Allergic Alveolitis
Interleukin-13
Interleukin-17
Toll-Like Receptor 9
Total Lung Capacity
Toll-Like Receptor 2
Interleukin-1
Lung
Compliance
Collagen
Th2 Cells
Interstitial Lung Diseases
Granuloma
Interleukin-4
Proteins
Fibrosis
Pathology
Antigens

All Science Journal Classification (ASJC) codes

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

Cite this

Chronic hypersensitivity pneumonitis caused by saccharopolyspora rectivirgula is not associated with a switch to a Th2 response. / Andrews, Kelly; Ghosh, Manik C.; Schwingshackl, Andreas; Rapalo, Gabriel; Luellen, Charlean; Waters, Christopher; Fitzpatrick, Elizabeth.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 310, No. 5, 01.03.2016, p. L393-L402.

Research output: Contribution to journalArticle

Andrews, Kelly ; Ghosh, Manik C. ; Schwingshackl, Andreas ; Rapalo, Gabriel ; Luellen, Charlean ; Waters, Christopher ; Fitzpatrick, Elizabeth. / Chronic hypersensitivity pneumonitis caused by saccharopolyspora rectivirgula is not associated with a switch to a Th2 response. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2016 ; Vol. 310, No. 5. pp. L393-L402.
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