H‐ficolin binds Aspergillus fumigatus leading to activation of the lectin complement pathway and modulation of lung epithelial immune responses

Stefan Bidula, Darren Sexton, Matthew Yates, Alireza Abdolrasouli, Anand Shah, Russell Wallis, Anna Reed, Darius Armstrong-James, Silke Schelenz

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Aspergillus fumigatus is an opportunistic fungal pathogen that typically infects the lungs of immunocompromised patients leading to a high mortality. H-Ficolin, an innate immune opsonin, is produced by type II alveolar epithelial cells and could participate in lung defences against infections. Here, we used the human type II alveolar epithelial cell line, A549, to determine the involvement of H-ficolin in fungal defence. Additionally, we investigated the presence of H-ficolin in bronchoalveolar lavage fluid from transplant patients during pneumonia. H-Ficolin exhibited demonstrable binding to A. fumigatus conidia via l-fucose, d-mannose and N-acetylglucosamine residues in a calcium- and pH-dependent manner. Moreover, recognition led to lectin complement pathway activation and enhanced fungal association with A549 cells. Following recognition, H-ficolin opsonization manifested an increase in interleukin-8 production from A549 cells, which involved activation of the intracellular signalling pathways mitogen-activated protein kinase MAPK kinase 1/2, p38 MAPK and c-Jun N-terminal kinase. Finally, H-ficolin concentrations were significantly higher in bronchoalveolar lavage fluid of patients with lung infections compared with control subjects (n = 16; P = 0·00726). Receiver operating characteristics curve analysis further highlighted the potential of H-ficolin as a diagnostic marker for lung infection (area under the curve = 0·77; P < 0·0001). Hence, H-ficolin participates in A. fumigatus defence through the activation of the lectin complement pathway, enhanced fungus–host interactions and modulated immune responses.
Original languageEnglish
Pages (from-to)281-291
Number of pages11
JournalImmunology
Volume146
Issue number2
Early online date24 Aug 2015
DOIs
Publication statusPublished - Oct 2015

Fingerprint

Mannose-Binding Lectin Complement Pathway
Aspergillus fumigatus
Lung
MAP Kinase Kinase 1
Alveolar Epithelial Cells
Bronchoalveolar Lavage Fluid
MAP Kinase Kinase 2
Infection
Opsonin Proteins
Fungal Spores
Fucose
Acetylglucosamine
ficolin
JNK Mitogen-Activated Protein Kinases
Complement Activation
Immunocompromised Host
p38 Mitogen-Activated Protein Kinases
Mannose
Interleukin-8
ROC Curve

Keywords

  • Aspergillus
  • complement
  • ficolin
  • innate immunity

Cite this

H‐ficolin binds Aspergillus fumigatus leading to activation of the lectin complement pathway and modulation of lung epithelial immune responses. / Bidula, Stefan; Sexton, Darren; Yates, Matthew; Abdolrasouli, Alireza; Shah, Anand; Wallis, Russell; Reed, Anna; Armstrong-James, Darius; Schelenz, Silke.

In: Immunology, Vol. 146, No. 2, 10.2015, p. 281-291.

Research output: Contribution to journalArticle

Bidula, S, Sexton, D, Yates, M, Abdolrasouli, A, Shah, A, Wallis, R, Reed, A, Armstrong-James, D & Schelenz, S 2015, 'H‐ficolin binds Aspergillus fumigatus leading to activation of the lectin complement pathway and modulation of lung epithelial immune responses', Immunology, vol. 146, no. 2, pp. 281-291. https://doi.org/10.1111/imm.12501
Bidula, Stefan ; Sexton, Darren ; Yates, Matthew ; Abdolrasouli, Alireza ; Shah, Anand ; Wallis, Russell ; Reed, Anna ; Armstrong-James, Darius ; Schelenz, Silke. / H‐ficolin binds Aspergillus fumigatus leading to activation of the lectin complement pathway and modulation of lung epithelial immune responses. In: Immunology. 2015 ; Vol. 146, No. 2. pp. 281-291.
@article{9b1c74e510e44c139eeae39be41bd952,
title = "H‐ficolin binds Aspergillus fumigatus leading to activation of the lectin complement pathway and modulation of lung epithelial immune responses",
abstract = "Aspergillus fumigatus is an opportunistic fungal pathogen that typically infects the lungs of immunocompromised patients leading to a high mortality. H-Ficolin, an innate immune opsonin, is produced by type II alveolar epithelial cells and could participate in lung defences against infections. Here, we used the human type II alveolar epithelial cell line, A549, to determine the involvement of H-ficolin in fungal defence. Additionally, we investigated the presence of H-ficolin in bronchoalveolar lavage fluid from transplant patients during pneumonia. H-Ficolin exhibited demonstrable binding to A. fumigatus conidia via l-fucose, d-mannose and N-acetylglucosamine residues in a calcium- and pH-dependent manner. Moreover, recognition led to lectin complement pathway activation and enhanced fungal association with A549 cells. Following recognition, H-ficolin opsonization manifested an increase in interleukin-8 production from A549 cells, which involved activation of the intracellular signalling pathways mitogen-activated protein kinase MAPK kinase 1/2, p38 MAPK and c-Jun N-terminal kinase. Finally, H-ficolin concentrations were significantly higher in bronchoalveolar lavage fluid of patients with lung infections compared with control subjects (n = 16; P = 0·00726). Receiver operating characteristics curve analysis further highlighted the potential of H-ficolin as a diagnostic marker for lung infection (area under the curve = 0·77; P < 0·0001). Hence, H-ficolin participates in A. fumigatus defence through the activation of the lectin complement pathway, enhanced fungus–host interactions and modulated immune responses.",
keywords = "Aspergillus , complement, ficolin, innate immunity",
author = "Stefan Bidula and Darren Sexton and Matthew Yates and Alireza Abdolrasouli and Anand Shah and Russell Wallis and Anna Reed and Darius Armstrong-James and Silke Schelenz",
note = "Acknowledgements The authors would like to acknowledge Professor Christopher Thornton (University of Exeter) for providing lateral-flow devices and Dr Chris Furze for providing complement reagents. S.B., A.A., M.Y., A.S and A.R. per-formed the experiments. S.B., D.W.S., R.W., D.A.J. and S.S designed the experiments. S.B., D.W.S. and S.S. wrote the manuscript. This work was supported by the Imperial College Healthcare Biomedical Research Centre, the Royal Brompton and Harefield Respiratory Biomedical Research Unit, the Medical Research Council (MR/K002708/1 to A.A., A.S., A.R. and D.A.J.) and the Faculty of Health,University of East Anglia (PhD studentship FMH 04.4.66C4 to S.B., D.W.S. and S.S.)",
year = "2015",
month = "10",
doi = "10.1111/imm.12501",
language = "English",
volume = "146",
pages = "281--291",
journal = "Immunology",
issn = "0019-2805",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - H‐ficolin binds Aspergillus fumigatus leading to activation of the lectin complement pathway and modulation of lung epithelial immune responses

AU - Bidula, Stefan

AU - Sexton, Darren

AU - Yates, Matthew

AU - Abdolrasouli, Alireza

AU - Shah, Anand

AU - Wallis, Russell

AU - Reed, Anna

AU - Armstrong-James, Darius

AU - Schelenz, Silke

N1 - Acknowledgements The authors would like to acknowledge Professor Christopher Thornton (University of Exeter) for providing lateral-flow devices and Dr Chris Furze for providing complement reagents. S.B., A.A., M.Y., A.S and A.R. per-formed the experiments. S.B., D.W.S., R.W., D.A.J. and S.S designed the experiments. S.B., D.W.S. and S.S. wrote the manuscript. This work was supported by the Imperial College Healthcare Biomedical Research Centre, the Royal Brompton and Harefield Respiratory Biomedical Research Unit, the Medical Research Council (MR/K002708/1 to A.A., A.S., A.R. and D.A.J.) and the Faculty of Health,University of East Anglia (PhD studentship FMH 04.4.66C4 to S.B., D.W.S. and S.S.)

PY - 2015/10

Y1 - 2015/10

N2 - Aspergillus fumigatus is an opportunistic fungal pathogen that typically infects the lungs of immunocompromised patients leading to a high mortality. H-Ficolin, an innate immune opsonin, is produced by type II alveolar epithelial cells and could participate in lung defences against infections. Here, we used the human type II alveolar epithelial cell line, A549, to determine the involvement of H-ficolin in fungal defence. Additionally, we investigated the presence of H-ficolin in bronchoalveolar lavage fluid from transplant patients during pneumonia. H-Ficolin exhibited demonstrable binding to A. fumigatus conidia via l-fucose, d-mannose and N-acetylglucosamine residues in a calcium- and pH-dependent manner. Moreover, recognition led to lectin complement pathway activation and enhanced fungal association with A549 cells. Following recognition, H-ficolin opsonization manifested an increase in interleukin-8 production from A549 cells, which involved activation of the intracellular signalling pathways mitogen-activated protein kinase MAPK kinase 1/2, p38 MAPK and c-Jun N-terminal kinase. Finally, H-ficolin concentrations were significantly higher in bronchoalveolar lavage fluid of patients with lung infections compared with control subjects (n = 16; P = 0·00726). Receiver operating characteristics curve analysis further highlighted the potential of H-ficolin as a diagnostic marker for lung infection (area under the curve = 0·77; P < 0·0001). Hence, H-ficolin participates in A. fumigatus defence through the activation of the lectin complement pathway, enhanced fungus–host interactions and modulated immune responses.

AB - Aspergillus fumigatus is an opportunistic fungal pathogen that typically infects the lungs of immunocompromised patients leading to a high mortality. H-Ficolin, an innate immune opsonin, is produced by type II alveolar epithelial cells and could participate in lung defences against infections. Here, we used the human type II alveolar epithelial cell line, A549, to determine the involvement of H-ficolin in fungal defence. Additionally, we investigated the presence of H-ficolin in bronchoalveolar lavage fluid from transplant patients during pneumonia. H-Ficolin exhibited demonstrable binding to A. fumigatus conidia via l-fucose, d-mannose and N-acetylglucosamine residues in a calcium- and pH-dependent manner. Moreover, recognition led to lectin complement pathway activation and enhanced fungal association with A549 cells. Following recognition, H-ficolin opsonization manifested an increase in interleukin-8 production from A549 cells, which involved activation of the intracellular signalling pathways mitogen-activated protein kinase MAPK kinase 1/2, p38 MAPK and c-Jun N-terminal kinase. Finally, H-ficolin concentrations were significantly higher in bronchoalveolar lavage fluid of patients with lung infections compared with control subjects (n = 16; P = 0·00726). Receiver operating characteristics curve analysis further highlighted the potential of H-ficolin as a diagnostic marker for lung infection (area under the curve = 0·77; P < 0·0001). Hence, H-ficolin participates in A. fumigatus defence through the activation of the lectin complement pathway, enhanced fungus–host interactions and modulated immune responses.

KW - Aspergillus

KW - complement

KW - ficolin

KW - innate immunity

U2 - 10.1111/imm.12501

DO - 10.1111/imm.12501

M3 - Article

VL - 146

SP - 281

EP - 291

JO - Immunology

JF - Immunology

SN - 0019-2805

IS - 2

ER -