The minor house dust mite allergen Der p 13 is a fatty acid binding protein and an activator of a TLR2-mediated innate immune response

Satitsuksanoa, P. et al. (2016) The minor house dust mite allergen Der p 13 is a fatty acid binding protein and an activator of a TLR2-mediated innate immune response. Allergy, 71(10), pp. 1425-1434. (doi:10.1111/all.12899) (PMID:27018864)

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Abstract

Background: The house dust mite (HDM) allergen Der p 13 could be a lipid-binding protein able to activate key innate signaling pathways in the initiation of the allergic response. We investigated the IgE reactivity of recombinant Der p 13 (rDer p 13), its lipid binding activities and its capacity to stimulate airway epithelium cells. Methods: Purified rDer p 13 was characterized by mass spectrometry, circular dichroism, fluorescence-based lipid binding assays and in-silico structural prediction. IgE binding activity and allergenic potential of Der p 13 were examined by ELISA, basophil degranulation assays and in-vitro airway epithelial cell activation assays. Results: Protein modeling and biophysical analysis indicated that Der p 13 adopts a β barrel structure with a predominately apolar pocket representing a potential binding site for hydrophobic ligands. Fluorescent lipid binding assays confirmed that the protein is highly selective for ligands and that it binds a fatty acid with a dissociation constant typical of lipid transporter proteins. The low IgE binding frequency (7%, n= 224) in Thai HDM-allergic patients as well as the limited propensity to activate basophil degranulation classifies Der p 13 as a minor HDM allergen. Nevertheless, the protein with its presumptively associated lipid(s) triggered the production of IL-8 and GM-CSF in respiratory epithelial cells through a TLR2-, MyD88-, NF-kB- and MAPK-dependent signaling pathway. Conclusions: Although a minor allergen, Der p 13 may, through its lipid binding capacity, play a role in the initiation of the HDM allergic response through TLR2 activation.

Item Type:Articles
Additional Information:The authors warmly thank the Mite Allergy Research Cohort (MARC) study team for the sera as well as clinical data collections. This work was partly funded by 90th Anniversary of Chulalongkorn University Scholarship under the Ratchadaphisek Somphot Fund, RSA56 Thailand Research Fund and by National Research University project office of Higher Education Commission (WCU003-HR57). Kiat Ruxrungtham is supported by the Senior Research Scholar of the Thailand Research Fund, and the Research Professor Program of Chulalongkorn University, Bangkok, Thailand.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Kennedy, Professor Malcolm and Satitsuksanoa, Miss Pattraporn
Authors: Satitsuksanoa, P., Kennedy, M., Gilis, D., Le Mignon, M., Suratannon, N., Soh, W. T., Wongpiyabovorn, J., Chatchatee, P., Vangveravong, M., Rerkpattanapipat, T., Sangasapaviliya, A., Piboonpocanun, S., Nony, E., Ruxrungtham, K., and Jacquet, A.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Allergy
Publisher:Wiley
ISSN:0105-4538
ISSN (Online):1398-9995
Published Online:29 April 2016
Copyright Holders:Copyright © 2016 Wiley
First Published:First published in Allergy 71(10): 1425-1434
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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