Αρχειοθήκη ιστολογίου

Δευτέρα 22 Ιανουαρίου 2018

The Blomia tropicalis allergen Blo t 7 stimulates innate immune signaling pathways through TLR2

Abstract

Background

Although the house dust mite species Blomia tropicalis is a leading cause of allergic diseases in tropical and subtropical regions, the identification and characterization of the allergenic proteins remains incomplete.

Objective

We aimed to characterize a recombinant form of Blo t 7 (rBlo t 7) in terms of IgE reactivity, lipid binding activity and ability to stimulate innate immunity.

Methods

The mature Blo t 7 cDNA was cloned by PCR methods for the expression of a secreted form of the allergen in P. pastoris. The IgE reactivity to purified rBlo t 7 as well as the potential cross-reactivity with Der p 7 were determined by ELISA. The lipid binding capacity of rBlo t 7 was assayed using fluorescent lipid probes. The stimulation of TLR2 signaling pathway by rBlo t 7 was examined in cell activation and reporter assays.

Results

The amplified mature Blo t 7 cDNA revealed the presence of a 60 base pair insertion compared with the reference sequence registered in the GENBANK database. Multiple protein sequence alignments of group 7 mite allergens confirmed that this longer deduced amino acid sequence was the authentic Blo t 7 polypeptide chain. Analysis of IgE reactivity can classify rBlo t 7 as an intermediate B. tropicalis allergen which displayed weak cross-reactivity with Der p 7. Purified rBlo t 7 was shown to bind selectively the naturally fluorescent lipid probe cis-parinaric (cPNA) with a dissociation constant of 2 μM. The group 7 Blomia allergen stimulated the TLR2-, NF-kB- and MAPK-dependent production of IL-8 and GM-CSF in respiratory epithelial cells.

Conclusions & Clinical Relevance

Through its propensity to transport fatty acids/lipids and to stimulate TLR2 signaling pathways in airway epithelial cells, Blo t 7 can represent a key allergen for the initiation of the B. tropicalis-induced airway inflammation.

This article is protected by copyright. All rights reserved.



from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2G7h1CQ

Δεν υπάρχουν σχόλια:

Δημοσίευση σχολίου