Abstract
BackgroundAspergillus fumigatus is the main causative agent of aspergillosis. Infections rarely occur in immunocompetent individuals, indicating efficient clearance of conidia by pulmonary defense mechanisms. Other aspergilli like Aspergillus niger also cause infections but to a much lesser extent. Our previous studies showed that A. fumigatus and A. niger have different behavior in the presence of type II alveolar A549 epithelial cells. A. fumigatus conidia are more efficiently internalized by these cells and germination is delayed when compared to A. niger. In addition, hyphae that have escaped the epithelial cells grow parallel to the epithelium, while A. niger grows away from this cell layer.ResultsHere it is shown that global gene expression of A. fumigatus and A. niger is markedly different upon contact with A549 cells. A total of 545 and 473 genes of A. fumigatus and A. niger, respectively, were differentially expressed when compared to growth in the absence of A549 cells. Notably, only 53 genes (approximately 10%) were shared in these gene sets. The different response was also illustrated by the fact that only 4 out of 75 GO terms were shared that were enriched in the differentially expressed gene sets. The orthologues of A. fumigatus genes involved in hypoxia regulation and heat shock were also up-regulated in A. niger, whereas thioredoxin reductase and allergen genes were found up-regulated in A. fumigatus but down-regulated in A. niger. Infection with A. fumigatus resulted in only 62 up and 47 down-regulated genes in A549. These numbers were 17 and 34 in the case of A. niger. GO terms related with immune response were down-regulated upon exposure to A. fumigatus but not in the case of A. niger. This indicates that A. fumigatus reprograms A549 to be less immunologically alert.ConclusionsOur dual transcriptomic analysis supports earlier observations of a marked difference in life style between A. fumigatus and A. niger when grown in the presence of type II epithelial cells. The results indicate important differences in gene expression, amongst others down regulation of immune response genes in lung epithelial cells by A. fumigatus but not by A niger.
Highlights
Aspergillus fumigatus is the main causative agent of aspergillosis
Differential gene expression of A. fumigatus and A. niger during co-cultivation with A549 cells As previously described [18], we observed that a large proportion of conidia of A. fumigatus and A. niger were internalized and part of them had germinated 12 h after addition to A549 cells
Our study revealed that expression profiles of A. fumigatus and A. niger differed drastically after 12 h upon contact with A549 cell
Summary
Aspergillus fumigatus is the main causative agent of aspergillosis. Infections rarely occur in immunocompetent individuals, indicating efficient clearance of conidia by pulmonary defense mechanisms. Other aspergilli like Aspergillus niger cause infections but to a much lesser extent. Aspergillus fumigatus is an opportunistic pathogen that is distributed globally and found in a large variety of substrates such as soil, organic matter, and water bodies [1]. This saprophytic fungus mainly reproduces asexually by producing large amounts of 2–3 μm wide conidia that are dispersed to enable colonization of new substrates [2]. A. fumigatus is recognized as the causative agent in 90% of the cases of aspergillosis, indicating that this fungus has acquired a specific life style that favors colonization of humans and allows establishment of serious infections [6]. Mortality rates of intensive care unit patients with aspergillosis range between 30 and 90% depending on the immune state of the host and the stage of the infection [10]
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