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Interactions of an Emerging Fungal Pathogen Scedosporium aurantiacum with Human Lung Epithelial Cells

Jashanpreet Kaur1,2, Liisa Kautto1,2, Anahit Penesyan1,2

  • 1Department of Molecular Sciences, Macquarie University, Sydney, Australia.

Scientific Reports
|March 24, 2019
PubMed

Insights

Scedosporium aurantiacum conidia attach to lung cells and trigger an immune response. This study reveals the early infection steps and host defense mechanisms against this fungus.

Area of Science:

  • Medical Mycology
  • Infectious Diseases
  • Cell Biology

Background:

  • Scedosporium fungi, including Scedosporium aurantiacum, inhabit diverse environments and can infect humans, particularly those with cystic fibrosis.
  • The precise mechanisms by which Scedosporium fungi initiate infections, especially in the human lung, are not fully understood.
  • Investigating the initial interactions between Scedosporium conidia and lung epithelial cells is crucial for understanding pathogenesis.

Purpose of the Study:

  • To visualize and analyze the initial attachment and early infection steps of Scedosporium aurantiacum conidia on human lung epithelial cells in vitro.
  • To investigate the transcriptomic response of human alveolar epithelial cells upon exposure to S. aurantiacum conidia.
  • To elucidate the host's innate immune response pathways activated by S. aurantiacum infection.

Main Methods:

  • Co-incubation of Scedosporium aurantiacum conidia with A549 human lung epithelial cells.
  • Microscopic visualization to observe conidial attachment and germination.
  • Transcriptomic analysis (RNA sequencing) of A549 cells post-exposure.
  • Network analysis of differentially expressed genes to identify activated pathways.

Main Results:

  • High percentage (75-80%) of S. aurantiacum conidia attached to A549 cells within 4 hours, initiating germ tube formation.
  • Germinating conidia appeared to invade via intercellular spaces; no intracellular uptake by epithelial cells was observed.
  • Transcriptomic analysis revealed upregulation of genes related to cell repair and inflammation, indicating a host defense response.
  • Network analysis identified activation of the NF-kB pathway and subsequent release of pro-inflammatory cytokines.

Conclusions:

  • This study provides the first transcriptomic insight into the response of human alveolar epithelial cells to S. aurantiacum conidia.
  • S. aurantiacum initiates infection by adhering to and germinating on lung epithelial cells, triggering innate immune responses.
  • Understanding these early host-pathogen interactions is vital for developing strategies against Scedosporium-related lung infections.

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