Abstract
BackgroundGiven the complex nature of the responses that can occur in host-pathogen interactions, dual transcriptomics offers a powerful method of elucidating these interactions during infection. The gene expression patterns of Aspergillus fumigatus conidia or host cells have been reported in a number of previous studies, but each focused on only one of the interacting organisms. In the present study, we profiled simultaneously the transcriptional response of both A. fumigatus and human airway epithelial cells (AECs).Methodology16HBE14o- transformed bronchial epithelial cells were incubated with A. fumigatus conidia at 37°C for 6 hours, followed by genome-wide transcriptome analysis using human and fungal microarrays. Differentially expressed gene lists were generated from the microarrays, from which biologically relevant themes were identified. Human and fungal candidate genes were selected for validation, using RT-qPCR, in both 16HBE14o- cells and primary AECs co-cultured with conidia.Principal FindingsWe report that ontologies related to the innate immune response are activated by co-incubation with A. fumigatus condia, and interleukin-6 (IL-6) was confirmed to be up-regulated in primary AECs via RT-qPCR. Concomitantly, A. fumigatus was found to up-regulate fungal pathways involved in iron acquisition, vacuolar acidification, and formate dehydrogenase activity.ConclusionTo our knowledge, this is the first study to apply a dual organism transcriptomics approach to interactions of A. fumigatus conidia and human airway epithelial cells. The up-regulation of IL-6 by epithelia and simultaneous activation of several pathways by fungal conidia warrants further investigation as we seek to better understand this interaction in both health and disease. The cellular response of the airway epithelium to A. fumigatus is important to understand if we are to improve host-pathogen outcomes.
Highlights
Microarray technologies have enabled unbiased gene expression profiling in host-pathogen interactions [1]
A. fumigatus was found to up-regulate fungal pathways involved in iron acquisition, vacuolar acidification, and formate dehydrogenase activity. To our knowledge, this is the first study to apply a dual organism transcriptomics approach to interactions of A. fumigatus conidia and human airway epithelial cells
To assess whether co-incubation would lead to the uptake of A. fumigatus conidia by primary human airway epithelial cells (AECs), co-cultures were first visualized using incremental focal planes, to produce a Z-stack to form a three dimensional image by confocal microscopy
Summary
Microarray technologies have enabled unbiased gene expression profiling in host-pathogen interactions [1] Using such technology, one can interrogate both organisms at the transcriptome level, allowing characterization of the dynamic interaction between microbe and the host environment. One can interrogate both organisms at the transcriptome level, allowing characterization of the dynamic interaction between microbe and the host environment This includes defining mechanisms of microbe survival and the host’s identification of the microbe and its subsequent clearance. Given the complex nature of the responses that can occur in host-pathogen interactions, dual transcriptomics offers a powerful method of elucidating the nature of interactions during infection. Given the complex nature of the responses that can occur in host-pathogen interactions, dual transcriptomics offers a powerful method of elucidating these interactions during infection. We profiled simultaneously the transcriptional response of both A. fumigatus and human airway epithelial cells (AECs)
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