Expression profile analysis reveals that Aspergillus fumigatus but not Aspergillus niger makes type II epithelial
Natalia Escobar1, Ivan D Valdes1, Esther M Keizer1
1Microbiology & Institute of Biomembranes, Department of Biology, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands.
Background:
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 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.
Results:
Here 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.
Conclusions:
Our 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.
Insights
Aspergillus fumigatus and Aspergillus niger exhibit distinct interactions with lung epithelial cells, influencing gene expression differently. A. fumigatus actively suppresses immune responses in these cells, unlike A. niger.
Area of Science:
- Microbiology
- Immunology
- Genomics
Background:
- Aspergillus fumigatus is a primary cause of aspergillosis, with infections rare in immunocompetent individuals due to effective pulmonary defenses.
- Distinct behaviors of A. fumigatus and Aspergillus niger have been observed when interacting with type II alveolar A549 epithelial cells, including differences in conidia internalization and hyphal growth patterns.
Purpose of the Study:
- To investigate the global gene expression differences between A. fumigatus and A. niger upon contact with A549 epithelial cells.
- To elucidate the molecular mechanisms underlying the differential interactions of these two Aspergillus species with lung epithelial cells.
Main Methods:
- Dual transcriptomic analysis comparing gene expression of A. fumigatus and A. niger grown with and without A549 cells.
- Gene Ontology (GO) term enrichment analysis to identify functional differences in gene expression.
Main Results:
- Marked differences in global gene expression were observed for both A. fumigatus (545 genes) and A. niger (473 genes) upon contact with A549 cells, with only ~10% shared genes.
- A. fumigatus infection led to the downregulation of immune response-related GO terms in A549 cells, indicating a reprogramming of the host cells.
- Specific gene sets, including those related to hypoxia and heat shock, were differentially regulated between the two species.
Conclusions:
- Dual transcriptomic analysis confirms distinct lifestyles of A. fumigatus and A. niger in the presence of type II epithelial cells.
- A. fumigatus actively downregulates immune response genes in lung epithelial cells, a mechanism not observed with A. niger, contributing to its pathogenic potential.
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