Pulmonary immune responses to Aspergillus fumigatus in an immunocompetent mouse model of repeated exposures

Amanda D. Buskirk, Steven Templeton, Ajay P. Nayak, Justin M. Hettick, Brandon F. Law, Brett J. Green, Donald H. Beezhold

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Aspergillus fumigatus is a filamentous fungus that produces abundant pigmented conidia. Several fungal components have been identified as virulence factors, including melanin; however, the impact of these factors in a repeated exposure model resembling natural environmental exposures remains unknown. This study examined the role of fungal melanin in the stimulation of pulmonary immune responses using immunocompetent BALB/c mice in a multiple exposure model. It compared conidia from wild-type A. fumigatus to two melanin mutants of the same strain, Δarp2 (tan) or Δalb1 (white). Mass spectrometry-based analysis of conidial extracts demonstrated that there was little difference in the protein fingerprint profiles between the three strains. Field emission scanning electron microscopy demonstrated that the immunologically inert Rodlet A layer remained intact in melanin-deficient conidia. Thus, the primary difference between the strains was the extent of melanization. Histopathology indicated that each A. fumigatus strain induced lung inflammation, regardless of the extent of melanization. In mice exposed to Δalb1 conidia, an increase in airway eosinophils and a decrease in neutrophils and CD8+ IL-17+ (Tc17) cells were observed. Additionally, it was shown that melanin mutant conidia were more rapidly cleared from the lungs than wild-type conidia. These data suggest that the presence of fungal melanin may modulate the pulmonary immune response in a mouse model of repeated exposures to A. fumigatus conidia.

Original languageEnglish
Pages (from-to)180-189
Number of pages10
JournalJournal of Immunotoxicology
Volume11
Issue number2
DOIs
StatePublished - 2014

Fingerprint

Aspergillus fumigatus
Fungal Spores
Aspergillus
Melanins
Lung
Fungal Structures
Interleukin-17
Virulence Factors
Peptide Mapping
Fungi
Field emission
Environmental Exposure
Mass spectrometry
Eosinophils
Electron Scanning Microscopy
Mass Spectrometry
Pneumonia
Neutrophils
Scanning electron microscopy
Proteins

Keywords

  • Aspergillus fumigatus
  • Immune response
  • Melanin
  • Tc17 cells

ASJC Scopus subject areas

  • Toxicology
  • Immunology
  • Medicine(all)

Cite this

Pulmonary immune responses to Aspergillus fumigatus in an immunocompetent mouse model of repeated exposures. / Buskirk, Amanda D.; Templeton, Steven; Nayak, Ajay P.; Hettick, Justin M.; Law, Brandon F.; Green, Brett J.; Beezhold, Donald H.

In: Journal of Immunotoxicology, Vol. 11, No. 2, 2014, p. 180-189.

Research output: Contribution to journalArticle

Buskirk, Amanda D. ; Templeton, Steven ; Nayak, Ajay P. ; Hettick, Justin M. ; Law, Brandon F. ; Green, Brett J. ; Beezhold, Donald H. / Pulmonary immune responses to Aspergillus fumigatus in an immunocompetent mouse model of repeated exposures. In: Journal of Immunotoxicology. 2014 ; Vol. 11, No. 2. pp. 180-189.
@article{9cd241fcee14436b9bdf92fe7a50e1aa,
title = "Pulmonary immune responses to Aspergillus fumigatus in an immunocompetent mouse model of repeated exposures",
abstract = "Aspergillus fumigatus is a filamentous fungus that produces abundant pigmented conidia. Several fungal components have been identified as virulence factors, including melanin; however, the impact of these factors in a repeated exposure model resembling natural environmental exposures remains unknown. This study examined the role of fungal melanin in the stimulation of pulmonary immune responses using immunocompetent BALB/c mice in a multiple exposure model. It compared conidia from wild-type A. fumigatus to two melanin mutants of the same strain, Δarp2 (tan) or Δalb1 (white). Mass spectrometry-based analysis of conidial extracts demonstrated that there was little difference in the protein fingerprint profiles between the three strains. Field emission scanning electron microscopy demonstrated that the immunologically inert Rodlet A layer remained intact in melanin-deficient conidia. Thus, the primary difference between the strains was the extent of melanization. Histopathology indicated that each A. fumigatus strain induced lung inflammation, regardless of the extent of melanization. In mice exposed to Δalb1 conidia, an increase in airway eosinophils and a decrease in neutrophils and CD8+ IL-17+ (Tc17) cells were observed. Additionally, it was shown that melanin mutant conidia were more rapidly cleared from the lungs than wild-type conidia. These data suggest that the presence of fungal melanin may modulate the pulmonary immune response in a mouse model of repeated exposures to A. fumigatus conidia.",
keywords = "Aspergillus fumigatus, Immune response, Melanin, Tc17 cells",
author = "Buskirk, {Amanda D.} and Steven Templeton and Nayak, {Ajay P.} and Hettick, {Justin M.} and Law, {Brandon F.} and Green, {Brett J.} and Beezhold, {Donald H.}",
year = "2014",
doi = "10.3109/1547691X.2013.819054",
language = "English",
volume = "11",
pages = "180--189",
journal = "Journal of Immunotoxicology",
issn = "1547-691X",
publisher = "Informa Healthcare",
number = "2",

}

TY - JOUR

T1 - Pulmonary immune responses to Aspergillus fumigatus in an immunocompetent mouse model of repeated exposures

AU - Buskirk, Amanda D.

AU - Templeton, Steven

AU - Nayak, Ajay P.

AU - Hettick, Justin M.

AU - Law, Brandon F.

AU - Green, Brett J.

AU - Beezhold, Donald H.

PY - 2014

Y1 - 2014

N2 - Aspergillus fumigatus is a filamentous fungus that produces abundant pigmented conidia. Several fungal components have been identified as virulence factors, including melanin; however, the impact of these factors in a repeated exposure model resembling natural environmental exposures remains unknown. This study examined the role of fungal melanin in the stimulation of pulmonary immune responses using immunocompetent BALB/c mice in a multiple exposure model. It compared conidia from wild-type A. fumigatus to two melanin mutants of the same strain, Δarp2 (tan) or Δalb1 (white). Mass spectrometry-based analysis of conidial extracts demonstrated that there was little difference in the protein fingerprint profiles between the three strains. Field emission scanning electron microscopy demonstrated that the immunologically inert Rodlet A layer remained intact in melanin-deficient conidia. Thus, the primary difference between the strains was the extent of melanization. Histopathology indicated that each A. fumigatus strain induced lung inflammation, regardless of the extent of melanization. In mice exposed to Δalb1 conidia, an increase in airway eosinophils and a decrease in neutrophils and CD8+ IL-17+ (Tc17) cells were observed. Additionally, it was shown that melanin mutant conidia were more rapidly cleared from the lungs than wild-type conidia. These data suggest that the presence of fungal melanin may modulate the pulmonary immune response in a mouse model of repeated exposures to A. fumigatus conidia.

AB - Aspergillus fumigatus is a filamentous fungus that produces abundant pigmented conidia. Several fungal components have been identified as virulence factors, including melanin; however, the impact of these factors in a repeated exposure model resembling natural environmental exposures remains unknown. This study examined the role of fungal melanin in the stimulation of pulmonary immune responses using immunocompetent BALB/c mice in a multiple exposure model. It compared conidia from wild-type A. fumigatus to two melanin mutants of the same strain, Δarp2 (tan) or Δalb1 (white). Mass spectrometry-based analysis of conidial extracts demonstrated that there was little difference in the protein fingerprint profiles between the three strains. Field emission scanning electron microscopy demonstrated that the immunologically inert Rodlet A layer remained intact in melanin-deficient conidia. Thus, the primary difference between the strains was the extent of melanization. Histopathology indicated that each A. fumigatus strain induced lung inflammation, regardless of the extent of melanization. In mice exposed to Δalb1 conidia, an increase in airway eosinophils and a decrease in neutrophils and CD8+ IL-17+ (Tc17) cells were observed. Additionally, it was shown that melanin mutant conidia were more rapidly cleared from the lungs than wild-type conidia. These data suggest that the presence of fungal melanin may modulate the pulmonary immune response in a mouse model of repeated exposures to A. fumigatus conidia.

KW - Aspergillus fumigatus

KW - Immune response

KW - Melanin

KW - Tc17 cells

UR - http://www.scopus.com/inward/record.url?scp=84897586092&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897586092&partnerID=8YFLogxK

U2 - 10.3109/1547691X.2013.819054

DO - 10.3109/1547691X.2013.819054

M3 - Article

C2 - 23919459

AN - SCOPUS:84897586092

VL - 11

SP - 180

EP - 189

JO - Journal of Immunotoxicology

JF - Journal of Immunotoxicology

SN - 1547-691X

IS - 2

ER -