title: Chronic hypersensitivity pneumonitis caused by Saccharopolyspora rectivirgula is not associated with a switch to a Th2 response.
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 wild-type (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.
authors.affiliation: Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee;
authors.forename: Kelly
authors.initials: K
authors.lastname: Andrews
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee; and.
authors.forename: Manik C
authors.initials: MC
authors.lastname: Ghosh
authors.affiliation: Mattel Children's Hospital at University of California Los Angeles, Department of Pediatrics, Los Angeles, California.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schwingshackl
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee; and.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Rapalo
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee; and.
authors.forename: Charlean
authors.initials: C
authors.lastname: Luellen
authors.affiliation: Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee; and.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Waters
authors.affiliation: Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee; efitzpatrick@uthsc.edu.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Fitzpatrick
mesh_terms: D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology* / Q000473:pathology*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D020381:Interleukin-17 / Q000276:immunology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016930:Saccharopolyspora; D018418:Th2 Cells / Q000166:cytology* / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000172:deficiency / Q000378:metabolism
chemical_list: D016207:Cytokines; D020381:Interleukin-17; C493486:Tlr2 protein, mouse; C495370:Tlr9 protein, mouse; D051195:Toll-Like Receptor 2; D051217:Toll-Like Receptor 9
keywords: Toll-like receptors 2 and 9; fibrosis; hypersensitivity pneumonitis