In:
Journal of Innate Immunity, S. Karger AG, Vol. 6, No. 6 ( 2014), p. 846-859
Abstract:
In cystic fibrosis (CF), colonization of the airways with 〈 i 〉 Pseudomonas aeruginosa 〈 /i 〉 is associated with disease deterioration. The mechanism behind the disease progression is not fully understood. The present work shows that the antibacterial chemokine MIG/CXCL9 is present in the airways and in sputum of CF patients. MIG/CXCL9 showed high bactericidal activity against. 〈 i 〉 P. aeruginosa, 〈 /i 〉 including some strains from the airways of CF patients. Full-length MIG/CXCL9 was detected in sputum from healthy controls and CF patients colonized with 〈 i 〉 P. aeruginosa. 〈 /i 〉 However, degraded MIG/CXCL9 was only found in CF sputum. In vitro, elastase of 〈 i 〉 P. aeruginosa 〈 /i 〉 cleaved off a fragment of similar size and two additional fragments from MIG/CXCL9. The fragments showed less bactericidal activity against 〈 i 〉 P. aeruginosa 〈 /i 〉 compared with the full-length protein. The fragments did not activate the MIG/CXCL9 receptor CXCR3 (expressed e.g. by NK cells, mast cells, and activated T cells) but instead displayed noncompetitive inhibition. In vitro, a decrease in CXCR3-bearing cells was found within and in the proximity of the bronchial epithelium of CF lung tissue compared with controls. Taken together, both bactericidal and cell-recruiting activities of MIG/CXCL9 are corrupted by 〈 i 〉 P. aeruginosa 〈 /i 〉 through release of elastase, and this may contribute to impaired airway host defense in CF.
Type of Medium:
Online Resource
ISSN:
1662-811X
,
1662-8128
Language:
English
Publisher:
S. Karger AG
Publication Date:
2014
detail.hit.zdb_id:
2455818-7
