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To determine if differences in the severity of pulmonary infection in cystic fibrosis seen with late isolates of Pseudomonas aeruginosa and Burkholderia cepacia are associated with differences in the initial response of alveolar macrophages (AM) to these pathogens, we assessed gene expression changes in human AM in response to infection with a laboratory strain, early and late clinical isolates of P. aeruginosa, and B. cepacia. Analysis of gene expression changes at the RNA level using oligonucleotide microarrays, following exposure to laboratory P. aeruginosa strain PAK, showed significant (P &lt; 0.01) &gt;2.5-fold upregulation of 42 genes and &gt;2.5-fold downregulation of 45 genes. The majority of the changes in gene expression involved genes as part of inflammatory pathways and signaling systems. Interestingly, similar responses were observed following exposure of AM to early and late clinical isolates of P. aeruginosa, as well as with B. cepacia, suggesting that the more severe clinical outcome of infections with late clinical isolates of P. aeruginosa or with B. cepacia cannot be explained by differences in the early interactions of these organisms with the human AM, as reflected by the similarity of gene expression changes in response to exposure of AM to these pathogens.

Similarity of Gene Expression Patterns in Human Alveolar Macrophages in Response to Pseudomonas aeruginosa and Burkholderia cepacia