Gene expression in lung epithelial cells following interaction with Pneumocystis carinii and its specific life forms yields insights into host gene responses to infection.

Abstract

Pneumocystis spp. interacts with epithelial cells in the alveolar spaces of the lung. It is thought that the binding of Pneumocystis to host cell epithelium is needed for life cycle completion and proliferation. The effect of this interaction on lung epithelial cells has previously shown that the trophic form of this organism greatly inhibits p34cdc2 activity, a serine/threonine kinase required for transition from the G2 to M phase in the cell cycle. To gain further insight into the host response during Pneumocystis pneumonia infection, we used microarray technology to profile epithelial cell (A549) gene expression patterns following Pneumocystis carinii interaction. Furthermore, we isolated separate populations of cyst and trophic forms of P. carinii, which were then applied to the lung epithelial cells. Differential expression of genes involved in various cellular functions dependent on the specific P. carinii life form in contact with the A549 cell was identified. The reliability of our data was further confirmed by Northern blot analysis on a number of selected upregulated or downregulated transcripts. The transcriptional response to P. carinii was dominated by cytokines, apoptotic, and antiapoptosis-related genes. These results reveal several previously unknown effects of P. carinii on the lung epithelial cell and provide insight into the complex interactions of host and pathogen.