期刊
CLINICAL AND EXPERIMENTAL ALLERGY
卷 49, 期 3, 页码 378-390出版社
WILEY
DOI: 10.1111/cea.13278
关键词
allergen; Der p 5; house dust mite; innate immune signalling pathways; lipid binding protein; TLR2
资金
- National Research University Project, Office of Higher Education Commission [NRU59-003-HR]
- Chulalongkorn University [GRB-BSS_83_59_30_24]
- Wellcome Trust [083625]
- Center of Excellence on Medical Biotechnology (CEMB), S&T Postgraduate Education and Research Development Office (PERDO) [SB-60-003-03]
- Thai Research Fund [TRG5680005]
BackgroundProtein crystallographic studies suggest that the house dust mite (HDM) allergen Der p 5 potentially interacts with hydrophobic ligands. Der p 5, in association with its ligand(s), might therefore trigger innate immune signalling pathways in the airway epithelium and influence the initiation of the HDM-allergic response. ObjectiveWe investigated the lipid binding propensities of recombinant (r)Der p 5 and characterized the signalling pathways triggered by the allergen in airway epithelial cells. MethodsrDer p 5 was produced in Pichia pastoris and characterized by mass spectrometry, multi-angle light scattering and circular dichroism. Its interactions with hydrophobic ligands were investigated in fluorescence-based lipid binding assays and in-silico docking simulations. Innate immune signalling pathways triggered by rDer p 5 were investigated in airway epithelial cell activation assays invitro. ResultsBiophysical analysis showed that rDer p 5 was monomeric and adopted a similar -helix-rich fold at both physiological and acidic pH. Spectrofluorimetry experiments showed that rDer p 5 is able to selectively bind lipid ligands, but only under mild acidic pH conditions. Computer-based docking simulations identified potential binding sites for these ligands. This allergen, with putatively associated lipid(s), triggered the production of IL-8 in respiratory epithelial cells through a TLR2-, NF-kB- and MAPK-dependent signalling pathway. Conclusions and Clinical RelevanceDespite the fact that Der p 5 represents a HDM allergen of intermediate prevalence, our findings regarding its lipid binding and activation of TLR2 indicate that it could participate in the initiation of the HDM-allergic state.
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