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

Bidula, S and Sexton, DW and Yates, M and Abdolrasouli, A and Shah, A and Wallis, R and Reed, A and Armstrong-James, D and Schelenz, S (2015) H-ficolin binds Aspergillus fumigatus leading to activation of the lectin complement pathway and modulation of lung epithelial immune responses. Immunology. ISSN 1365-2567

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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 utilised 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 (BAL) 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 IL-8 production from A549 cells which involved activation of the intracellular signalling pathways MEK 1/2, p38 MAPK and JNK. Finally, H-ficolin concentrations were significantly higher in BAL of patients with lung infections compared to control subjects (n=16; p=0.00726). ROC curve analysis further highlighted the potential of H-ficolin as a diagnostic marker for lung infection (AUC=0.77; p<0.0001). Thus, H-ficolin participates in A. fumigatus defence via activation of the lectin complement pathway, enhanced fungal-host interactions and modulated immune responses. This article is protected by copyright. All rights reserved.

Item Type: Article
Additional Information: This is the accepted version of the following article: "H-ficolin binds Aspergillus fumigatus leading to activation of the lectin complement pathway and modulation of lung epithelial immune responses", which has been published in final form at http://dx.doi.org/doi:10.1111/imm12501. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Uncontrolled Keywords: 1107 Immunology, 1114 Paediatrics And Reproductive Medicine
Subjects: R Medicine > RC Internal medicine
R Medicine > RS Pharmacy and materia medica
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Wiley
Related URLs:
Date Deposited: 09 Jul 2015 13:56
Last Modified: 07 Sep 2015 14:44
DOI or Identification number: 10.1111/imm.12501
URI: http://researchonline.ljmu.ac.uk/id/eprint/1550

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