In an effort to review our current understanding of the host-pathogen interface driving CF pulmonary disease, we discuss (i) the progression of disease within the primitive CF lung, specifically focusing on the role of host versus bacterial factors; (ii) critical, neutrophil-derived innate immune effectors that are implicated in CF pulmonary disease, including reactive oxygen species (ROS) and antimicrobial peptides (e.g., LL-37); (iii) <i>P. aeruginosa</i> virulence factors and adaptive mutations that enable evasion of the host response; and (iv) ongoing work examining the distribution and colocalization of host and bacterial factors within distinct anatomical niches of the CF lung.
The pulmonary mucus of cystic fibrosis (CF) patients displays elevated levels of the cathelicidin antimicrobial peptideLL-37, and the aim of this work was to assess the effect of LL-37 on the growth of <i>Aspergillus fumigatus</i>, a common pathogen of CF patients.Exposure of <i>A. fumigatus</i> to LL-37 and its derived fragment RK-31 (1.95 μg/ml) for 24 h had a positive effect on growth (199.94% ± 6.172% [<i>P</i> < 0.05] and 218.20% ± 4.63% [<i>P</i> < 0.05], respectively), whereas scrambled LL-37 peptide did not (85.12% ± 2.92%).
CAP18 levels were elevated in CF and COPD patients compared to control subjects, while asthma patients had reduced CAP18 levels. uPA levels were similar but uPAR was elevated in CF and COPD patients more so than in asthma patients, while PAI-1 levels were elevated in all three disease groups.
Exposure of CF xenografts to an adenovirus expressing the human cathelicidin LL-37/hCAP-18 increased levels of this peptide in the ASF three- to fourfold above the normal concentrations, which were equivalent in ASF from CF and normal xenografts before gene transfer.