Pseudomonas Aeruginosa Counteracts the Host Defense Functions of Mig/Cxcl9

Pseudomonas aeruginosa is a frequent colonizer and cause of exacerbations in cystic fibrosis (CF) and other chronic pulmonary diseases. CF is a monogenic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. One feature of the disease is a reduction or absence of chloride transport and dysregulation of sodium transport to the airway epithelium surface. In this study, we show that the antibacterial chemokine MIG/CXCL9 (monokine induced by IFN-γ) is expressed by bronchial epithelial cells and could be detected in sputum from patients suffering from CF. MIG/CXCL9 showed high bactericidal activity against P. aeruginosa in vitro, also at salt concentrations similar to those seen in CF. P. aeruginosa strains equipped with efflux-pumps, showed a high degree of resistance to MIG/CXCL9. Elastase from P. aeruginosa and neutrophils respectively, both cleaved of a distinct fragment from the MIG/CXCL9 holoprotein. Taken together, our data indicates that the activity of antimicrobial proteins, as exemplified by MIG/CXCL9, is not foremost hampered by salt but rather efflux-pumps and proteases. The latter released both by the bacteria and neutrophils.