A murine inhalation model to characterize pulmonary exposure to dry aspergillus fumigatusconidia

Amanda D. Buskirk, Brett J. Green, Angela R. Lemons, Ajay P. Nayak, W. Travis Goldsmith, Michael L. Kashon, Stacey E. Anderson, Justin M. Hettick, Steven Templeton, Dori R. Germolec, Donald H. Beezhold

Research output: Contribution to journalArticle

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Abstract

Most murine models of fungal exposure are based on the delivery of uncharacterized extracts or liquid conidia suspensions using aspiration or intranasal approaches. Studies that model exposure to dry fungal aerosols using whole body inhalation have only recently been described. In this study, we aimed to characterize pulmonary immune responses following repeated inhalation of conidia utilizing an acoustical generator to deliver dry fungal aerosols to mice housed in a nose only exposure chamber. Immunocompetent female BALB/cJ mice were exposed to conidia derived from Aspergillus fumigatus wild-type (WT) or a melanin-deficient (δalb1) strain. Conidia were aerosolized and delivered to mice at an estimated deposition dose of 1×105 twice a week for 4 weeks (8 total). Histopathological and immunological endpoints were assessed 4, 24, 48, and 72 hours after the final exposure. Histopathological analysis showed that conidia derived from both strains induced lung inflammation, especially at 24 and 48 hour time points. Immunological endpoints evaluated in bronchoalveolar lavage fluid (BALF) and the mediastinal lymph nodes showed that exposure to WT conidia led to elevated numbers of macrophages, granulocytes, and lymphocytes. Importantly, CD8+ IL17+ (Tc17) cells were significantly higher in BALF and positively correlated with germination of A. fumigatus WT spores. Germination was associated with specific IgG to intracellular proteins while Dalb1 spores elicited antibodies to cell wall hydrophobin. These data suggest that inhalation exposures may provide a more representative analysis of immune responses following exposures to environmentally and occupationally prevalent fungal contaminants.

Original languageEnglish (US)
Article numbere109855
JournalPLoS One
Volume9
Issue number10
DOIs
StatePublished - Oct 23 2014
Externally publishedYes

Fingerprint

Fungal Spores
Aspergillus
Aerosols
Inhalation
conidia
breathing
lungs
Lung
Fluids
Lymphocytes
Macrophages
Melanins
mice
Suspensions
Aspergillus fumigatus
Immunoglobulin G
Cells
Bronchoalveolar Lavage Fluid
Impurities
Germination

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Buskirk, A. D., Green, B. J., Lemons, A. R., Nayak, A. P., Goldsmith, W. T., Kashon, M. L., ... Beezhold, D. H. (2014). A murine inhalation model to characterize pulmonary exposure to dry aspergillus fumigatusconidia. PLoS One, 9(10), [e109855]. https://doi.org/10.1371/journal.pone.0109855

A murine inhalation model to characterize pulmonary exposure to dry aspergillus fumigatusconidia. / Buskirk, Amanda D.; Green, Brett J.; Lemons, Angela R.; Nayak, Ajay P.; Goldsmith, W. Travis; Kashon, Michael L.; Anderson, Stacey E.; Hettick, Justin M.; Templeton, Steven; Germolec, Dori R.; Beezhold, Donald H.

In: PLoS One, Vol. 9, No. 10, e109855, 23.10.2014.

Research output: Contribution to journalArticle

Buskirk, AD, Green, BJ, Lemons, AR, Nayak, AP, Goldsmith, WT, Kashon, ML, Anderson, SE, Hettick, JM, Templeton, S, Germolec, DR & Beezhold, DH 2014, 'A murine inhalation model to characterize pulmonary exposure to dry aspergillus fumigatusconidia', PLoS One, vol. 9, no. 10, e109855. https://doi.org/10.1371/journal.pone.0109855
Buskirk AD, Green BJ, Lemons AR, Nayak AP, Goldsmith WT, Kashon ML et al. A murine inhalation model to characterize pulmonary exposure to dry aspergillus fumigatusconidia. PLoS One. 2014 Oct 23;9(10). e109855. https://doi.org/10.1371/journal.pone.0109855
Buskirk, Amanda D. ; Green, Brett J. ; Lemons, Angela R. ; Nayak, Ajay P. ; Goldsmith, W. Travis ; Kashon, Michael L. ; Anderson, Stacey E. ; Hettick, Justin M. ; Templeton, Steven ; Germolec, Dori R. ; Beezhold, Donald H. / A murine inhalation model to characterize pulmonary exposure to dry aspergillus fumigatusconidia. In: PLoS One. 2014 ; Vol. 9, No. 10.
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