IL-17A-expressing T cells are essential for bacterial clearance in a murine model of hypersensitivity pneumonitis.
Hypersensitivity pneumonitis (HP) is an inflammatory lung disease characterized by a diffuse mononuclear cell infiltrate in the lung that can progress to pulmonary fibrosis with chronic exposure to an inhaled Ag. We previously reported that C57BL/6 mice repeatedly exposed to the ubiquitous microorganism Bacillus subtilis develop mononuclear infiltrates in the lung that contain Vgamma6/Vdelta1(+) gammadelta T cells. In the absence of this T cell subset, mice treated with B. subtilis had significantly increased collagen deposition in the lung, suggesting a regulatory role for Vgamma6/Vdelta1(+) gammadelta T cells. To further investigate the role of Vgamma6/Vdelta1(+) gammadelta T cells in B. subtilis-induced lung fibrosis, we exposed transgenic Vgamma6/Vdelta1 mice to this microorganism and found decreased collagen content in the lung compared with wild-type C57BL/6 mice. Cytokine analysis of lung homogenates from wild-type C57BL/6 mice demonstrated increased IL-17A concentrations with repeated exposure to B. subtilis. In the absence of IL-17 receptor signaling, IL-17ra(-/-) mice had delayed clearance of B. subtilis with increased lung inflammation and fibrosis. Although IL-17A was predominantly expressed by Vgamma6/Vdelta1(+) T cells, a compensatory increase in IL-17A expression by CD4(+) T cells was seen in the absence of gammadelta T cells that resulted in similar levels of IL-17A in the lungs of TCRdelta(-/-) and wild-type C57BL/6 mice. In combination, our data suggest an important role for IL-17A-expressing T lymphocytes, both gammadelta and alphabeta T cells, in eliminating this microorganism that prevents excessive inflammation and eventual lung fibrosis in this murine model of B. subtilis-induced hypersensitivity pneumonitis.
Simonian
Philip L
PL
Department of Medicine, University of Colorado Denver, Aurora, CO 80045, USA. philip.simonian@ucdenver.edu
Roark
Christina L
CL
Wehrmann
Fabian
F
Lanham
Allison M
AM
Born
Willi K
WK
O'Brien
Rebecca L
RL
Fontenot
Andrew P
AP
D000542:Alveolitis, Extrinsic Allergic / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D000818:Animals; D001412:Bacillus subtilis; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D016908:Gram-Positive Bacterial Infections / Q000276:immunology* / Q000473:pathology; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011658:Pulmonary Fibrosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D053722:Receptors, Interleukin-17 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D016207:Cytokines; C491673:Il17ra protein, mouse; D020381:Interleukin-17; D053722:Receptors, Interleukin-17; D003094:Collagen