Investigating the Role of Airway Epithelium in Shaping Immune Response to Indoor Fungal Contaminant Exposure

Details

• Personal Author:
  Snoderly, Hunter ; Lemons, Angela R. ; Blackwood, Catherine ; Weaver, Kelly ; Green, Brett J. ; Croston, Tara L.
• Description:
  Rationale: The fungal contaminants Stachybotrys chartarum and Aspergillus versicolor modulate pulmonary immune responses in murine models of repeated exposure. These complex responses exhibit features of Th1 and Th2 immunity and are poorly defined. The respiratory epithelium acts as a barrier to inhaled fungi and modulates innate and adaptive immunity. Understanding how the respiratory epithelium facilitates anti-fungal immunity will support development of more advanced in vitro fungal exposure paradigms mimicking in vivo exposures. Methods: Murine pulmonary epithelial cells (MLE-12) were stimulated with five doses of live or heat-inactivated (HIC) S. chartarum or A. versicolor conidia for 48 hours; these were extrapolated from fungal deposition levels that provoked an immune response in prior murine exposures. To evaluate cytotoxicity, lactate dehydrogenase release was measured at four timepoints followed by a tetrazolium-based assay (MTS). Epithelial cell-secreted cytokines will be assessed by a multiplex bead-based immunoassay to define how these relate to responses observed during in vivo exposures. Results: Preliminary data indicate S. chartarum and A. versicolor impact in vitro epithelial cell viability, with S. chartarum producing toxicity at significantly (p<0.05, n=3 independent experiments) lower doses than A. versicolor. This occurred independently of conidia viability. In this model, calculated LC50s for live and HIC S. chartarum were 4.68*103 and 2.37*103 conidia/mL, respectively. For live and HIC A. versicolor, LC50s were 1.87*106 and 6.14*105 conidia/mL, respectively. Conclusions: This study illustrates that S. chartarum is more acutely toxic to MLE-12 cells than A. versicolor. Ongoing cytokine characterization may reveal how immune responses to these fungal contaminants are initiated and sustained. Description provided by NIOSH
• Subjects:
  • Fungi
  • Lung
  • Mycoses
  • Occupational Health
  • Safety
• Keywords:
  • Fungi; Fungal infections; Immune reaction; Lung cells; Cytokines; In vitro studies; Cellular effects; Inhalation
• Source:
  J Allergy Clin Immunol 2025 Feb; 155(2)(Suppl):AB126
• ISSN:
  0091-6749
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Chicago Region OSHA ; Indiana ; Philadelphia Region OSHA ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  2 pdf pages
• Volume:
  155
• Issue:
  2
• NIOSHTIC Number:
  nn:20071563
• Federal Fiscal Year:
  2025
• Peer Reviewed:
  False
• Download URL:
  https://stacks.cdc.gov/view/cdc/259338/cdc_259338_DS1.pdf
• File Type:
  [PDF - 262.50 KB]
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5d524138b7d3d9931142a6600ad8488e62f99a3acc0687dc64a5e99620b34097fc0a892c105882ceb26b31e294710edd926b91b2b86669fb2694aa56c4cb8a46