IL-17A-mediated expression of epithelial IL-17C promotes inflammation during acute Pseudomonas aeruginosa pneumonia.
Lung epithelial cells are suggested to promote pathogen-induced pulmonary inflammation by the release of chemokines, resulting in enhanced recruitment of circulating leukocytes. Recent studies have shown that the interleukin-17C (IL-17C) regulates innate immune functions of epithelial cells in an autocrine manner. The aim of this study was to investigate the contribution of IL-17C to pulmonary inflammation in a mouse model of acute Pseudomonas aeruginosa pneumonia. Infection with P. aeruginosa resulted in an increased expression of IL-17C in lung tissue of wild-type mice. Numbers of neutrophils and the expression of the neutrophil-recruiting chemokines keratinocyte-derived chemokine and macrophage inflammatory protein 2 were significantly decreased in lungs of IL-17C-deficient (IL-17C-/-) mice infected with P. aeruginosa at 24 h. Systemic concentrations of interleukin-6 (IL-6) were significantly decreased in infected IL-17C-/-mice at 24 h and the survival of IL-17C-/-mice was significantly increased at 48 h. The expression of IL-17C was reduced in infected mice deficient for interleukin-17A (IL-17A), whereas pulmonary concentrations of IL-17A were not affected by the deficiency for IL-17C. Stimulation of primary alveolar epithelial cells with IL-17A resulted in a significantly increased expression of IL-17C in vitro. Our data suggest that IL-17A-mediated expression of epithelial IL-17C amplifies the release of chemokines by epithelial cells and thereby contributes to the recruitment of neutrophils and systemic inflammation during acute P. aeruginosa pneumonia.
Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg, Germany.
Lisa
L
Wolf
Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland, Saarbrücken, Germany; and.
Sandra
S
Sapich
Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg, Germany.
Anja
A
Honecker
Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg, Germany.
Christopher
C
Jungnickel
Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg, Germany.
Frederik
F
Seiler
Institute of Medical Microbiology and Hygiene, Saarland University, Homburg, Germany.
Markus
M
Bischoff
Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg, Germany.
Bodo
B
Wonnenberg
Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg, Germany.
Christian
C
Herr
Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland, Saarbrücken, Germany; and.
Nicole
N
Schneider-Daum
Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland, Saarbrücken, Germany; and.|Biopharmaceutics and Pharmaceutical Technology, Department of Pharmacy, Saarland University, Saarbrücken, Germany.
Claus-Michael
CM
Lehr
Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg, Germany.
Robert
R
Bals
Department of Internal Medicine V-Pulmonology, Allergology and Respiratory Critical Care Medicine, Saarland University, Homburg, Germany; christoph.beisswenger@uks.eu.
Christoph
C
Beisswenger
D056809:Alveolar Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D020381:Interleukin-17 / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050296:Microbial Viability; D020556:Neutrophil Infiltration; D011014:Pneumonia / Q000150:complications / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D016019:Survival Analysis
D020381:Interleukin-17
IL-17A; IL-17C; P. aeruginosa; inflammation; pathology; pneumonia; sepsis