Differential gene expression of Aspergillus fumigatus and Aspergillus niger interacting with epithelial lung cells

Objective: Aspergillus fumigatus is the main causative agent of aspergillosis. Most infections occur in immunocompromised individuals, indicating an efficient clearance of conidia by the pulmonary defence system in immunocompetent individuals. Infections by other aspergilli like Aspergillus niger can occur, but to lesser extent. Previous studies showed that A. fumigatus and A. niger behave differently in the presence of type II alveolar A549 epithelial cells. A. fumigatus is more efficiently internalized by the A549 cells and shows a delay in germination, when compared to A. niger. The hyphae of A. fumigatus, that escaped the epithelial cells grow parallel to the epithelium, while the A. niger hyphae grow away from the epithelial cell layer. This study focusses on the gene expression of A. fumigatus and A. niger after co-cultivation with A549 cells. Our hypothesis is that the difference in lifestyle between the two aspergilli is also observed in the gene expression profiles. Methods: RNA of the co-cultivation of the A549 cells with A. fumigatus or A. niger was isolated and sequenced. The obtained RNA sequences were analysed with custom R and python scripts to obtain the differentially expressed genes and GO terms. Results: The obtained RNA sequences show big differences in the global gene expression of A. fumigatus and A. niger upon contact with A549 cells. A total of 545 and 473 genes for respectively A. fumigatus and A. niger were differently expressed when compared to growth in absence of A549 cells. Of these genes only 53 (∼10%) were shared between both species. The different response was also illustrated by the fact that only 4 GO terms were shared between the differentially expressed genes of both gene sets. Genes described in hypoxia regulation and heat shock were found up-regulated in A. fumigatus and their homologs in A. niger. The A. fumigatus thioredoxin reductase and allergen genes were found up-regulated in this fungus, but homologous genes were down-regulated in A. niger. After co-cultivation with A. fumigatus 62 genes were up and 47 genes were down-regulated in the A549 cells. Co-cultivation with A. niger resulted in 17 up and 34 down-regulated genes. GO term related with the immune response were down-regulated in the A549 cells upon exposure to A. fumigatus, but not in the case of A. niger. This is a strong indication that A. fumigatus reprograms the A549 cells to be immunologically less alert. Conclusion: Our dual transcriptome analysis supports earlier observations of a markedly difference in life style between A. fumigatus and A. niger when grown in presence of type II epithelial lung cells. These results show an important difference in gene expression, amongst others the downregulation of immune response genes in epithelial cells by A. fumigatus and not by A. niger