AUTHOR=Hu Rei-Hsing , Wu Chia-Ta , Wu Ting-Shuan , Yu Feng-Yih , Ko Jiunn-Liang , Lue Ko-Huang , Liu Yu-Fan 

TITLE=Systematic Characterization of the Group 2 House Dust Mite Allergen in Dermatophagoides microceras

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=11

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.793559

DOI=10.3389/fcimb.2021.793559

ISSN=2235-2988

ABSTRACT=<sec><title>Background</title><p>Allergic asthma, a chronic airway inflammatory disease, is a critical public health problem. Indoor house dust mites (HDMs) could cause allergic asthma. The prevalence of sensitization to <italic>Dermatophagoides microceras</italic> (<italic>Der m</italic>) was approximately 80% and is related to the immunoglobulin E crossing-reactivity of mites belonging to the same genus, <italic>Dermatophagoides pteronyssinus</italic> (<italic>Der p</italic>) and <italic>Dermatophagoides farina</italic> (<italic>Der f</italic>). However, studies on <italic>Der m</italic> are scant.</p></sec><sec><title>Methods</title><p>We used integrated OMICs approaches to identify and characterize the group 2 mite allergen-like protein in <italic>Der m</italic> (<italic>Der m 2</italic>). We established a <italic>Der m 2</italic>-induced allergic asthma mouse model and treated the mice with a fungal immunomodulatory protein (FIP-<italic>fve</italic>) isolated from <italic>Flammulina veluptipes</italic> to evaluate the allergenicity of <italic>Der m 2</italic> and the immunomodulatory effects of FIP-<italic>fve</italic>.</p></sec><sec><title>Results</title><p>By performing <italic>de novo</italic> draft genome assembly and comparative genome analysis, we identified the putative 144-amino acid <italic>Der m 2 in silico</italic> and further confirmed its existence through liquid chromatography–tandem mass spectrometry. <italic>Der m 2</italic> is a lipopolysaccharides (LPS)-binding protein. Thus, we examined the LPS-binding activity of recombinant <italic>Der m 2</italic> by performing molecular docking analysis, co-immunoprecipitation (Co-IP), and a pull-down assay. <italic>Der m 2</italic> elicited the production of pro-inflammatory cytokines, interleukin (IL)-6, and IL-8 in BEAS-2B cells, a human bronchial epithelial cell line, and induced airway hyperresponsiveness in mice. Furthermore, in mice sensitized with <italic>Der m 2</italic>, the administration of FIP-<italic>fve</italic> in either the earlier stage or the late stage, FIP-<italic>fve</italic> alleviated allergic asthma by moderating airway inflammation and remodeling.</p></sec><sec><title>Conclusions</title><p><italic>Der m 2</italic> induced inflammatory responses in cell and mouse models. FIP-<italic>fve</italic> alleviated inflammation in <italic>Der m 2</italic>-induced asthma in mice by exerting an immunomodulatory effect.</p></sec>