title: Dual organism transcriptomics of airway epithelial cells interacting with conidia of Aspergillus fumigatus.
abstract: BACKGROUND
  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. 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).
  
  
  METHODS
  16HBE14o- 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  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. 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.
authors.affiliation: UBC James Hogg Research Centre, Institute for HEART+LUNG Health, Providence Health Care, Vancouver, British Columbia, Canada.
authors.forename: Jean L
authors.initials: JL
authors.lastname: Oosthuizen
authors.forename: Pol
authors.initials: P
authors.lastname: Gomez
authors.forename: Jian
authors.initials: J
authors.lastname: Ruan
authors.forename: Tillie L
authors.initials: TL
authors.lastname: Hackett
authors.forename: Margo M
authors.initials: MM
authors.lastname: Moore
authors.forename: Darryl A
authors.initials: DA
authors.lastname: Knight
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Tebbutt
mesh_terms: D001232:Aspergillus fumigatus / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism* / Q000382:microbiology*; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D018613:Microscopy, Confocal; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013172:Spores, Fungal / Q000235:genetics* / Q000502:physiology
chemical_list: D015850:Interleukin-6