Elucidating the Role of IL-5 in the Pulmonary Response to Inhalation of Aspergillus versicolor and Stachybotrys chartarum Using a Murine IL-5 Knockout Model

Details

• Personal Author:
  Weaver, K. L.
• Description:
  Background and Purpose: A changing climate has resulted in an increased frequency and severity of hurricanes and flooding that devastate communities and leave structures inundated with water. Water damage in buildings promotes growth of fungal species that can be harmful to human health. This is of concern given that humans spend over 90% of their time indoors - whether that be at home, work, or school. Aspergillus versicolor and Stachybotrys chartarum are two fungal species commonly found in damp indoor environments. Inhalation of fungal spores can lead to lung inflammation and development of allergic disease. Interleukin-5 (IL-5) is a mediator of the inflammatory allergic response and is a clinical target for treatment; however, further research is needed to fully understand the role of IL-5 in response to fungal exposure, how sex as a biological variable influences this process, and to ultimately develop tools to assess exposure and treatments to mitigate respiratory ailments. Methods: Male and female C57BL/6J or IL-5 genetic knockout mice were nose-only exposed to HEPA-filtered air, 3x105 viable A. versicolor spores, or 1x104 viable S. chartarum spores for up to one hour, twice weekly, for 13 weeks using an acoustical aerosol generator system. The dose for each fungal species was the estimated pulmonary deposition per exposure. Functional respiratory assessment was performed using whole body plethysmography at week 0, week 4, week 8, and week 13 allowing for repeat measures of individual mice over time. Mice were euthanized 24 hours following the final exposure and immunologically relevant tissues were collected to assess local and systemic immune responses. Pulmonary responses were further assessed by lung histopathology, quantification of immunoglobulins in sera, flow cytometry analysis of immune cell populations in murine tissues, and measurement of Th1 and Th2 associated genes using quantitative polymerase chain reaction. Results: Preliminary data suggests that sex is an important factor to consider in the response to the inhalation of A. versicolor and S. chartarum in this mouse model. Whole body plethysmography indicated that overall, females have lower respiratory function than males in wild-type mice exposed to air only at baseline. Exposure to S. chartarum led to a decrease in respiratory function as measured by tidal volume in IL-5 -/- female mice compared to male mice after 13 weeks of exposures. Histology and flow cytometry showed increases in immune cell infiltration into the lung and the development of adaptive immune responses in mice exposed to fungal spores compared to air only control mice. Preliminary analysis exhibited that the mechanisms by which these pulmonary responses develop differed following A. versicolor and S. chartarum exposure. Conclusions: IL-5 is a clinical target for treatment in allergic airway disease due to its role in the inflammatory response and differentiation of eosinophils. It is imperative to investigate the role of IL-5 in the response to fungal exposure given that anti-IL-5 therapies often inhibit the function of IL-5 in humans. The goal was to understand how the immune response differs following exposure to two common fungal contaminants, focusing specifically on the role of IL-5 and the influence of sex as a biological variable. Together, these data provided insights on the mechanisms of the immune response to fungal exposure that can be applied to the assessment of fungal-related respiratory disease in humans. Description provided by NIOSH
• Subjects:
  • Fungi
  • Hypersensitivity
  • Mycoses
  • Occupational Health
  • Respiratory System
  • Safety
• Keywords:
  • Fungi; Fungal infections; Allergies; Allergic reactions; Lung irritants; Immune reaction; Histopathology; Laboratory animals; Respiratory function
• Source:
  Toxicologist 2025 Mar; 204(S1):252
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  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:
  204
• NIOSHTIC Number:
  nn:20071578
• Federal Fiscal Year:
  2025
• Peer Reviewed:
  False
• Download URL:
  https://stacks.cdc.gov/view/cdc/259353/cdc_259353_DS1.pdf
• File Type:
  [PDF - 279.17 KB]
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:286491d71f4d875073088ae889798c8258e5cfb013f97ecb894333e57cfd6e8d139443124d7c310fd0f9051712e280aba6bf5feaac7b15dcbd6402db34a59fdc