Innate immune responses of airway epithelium to house dust mite are mediated through beta-glucan-dependent pathways.
BACKGROUND
House dust mite (HDM) induces allergic asthma in sensitized individuals, although the mechanisms by which HDM is sensed and recognized by the airway mucosa, leading to dendritic cell (DC) recruitment, activation, and subsequent T(H)2-mediated responses, are unknown.


OBJECTIVE
We sought to define the pathways by which HDM activates respiratory epithelium to induce allergic airway responses.


METHODS
Using a human airway epithelial cell line (16HBE14o-), we studied secretion of the DC chemokine CCL20 after exposure to HDM or other allergens, investigated components of the HDM responsible for the induction of chemokine release, and examined activation of signaling pathways. Central findings were also confirmed in primary human bronchial cells.


RESULTS
We demonstrate that exposure of airway epithelium to HDM results in specific and rapid secretion of CCL20, a chemokine attractant for immature DCs. The induction of CCL20 secretion is dose and time dependent and quite specific to HDM because other allergens, such as ragweed pollen and cockroach antigen, fail to significantly induce CCL20 secretion. Induction of CCL20 secretion is not protease or Toll-like receptor 2/4 dependent but, interestingly, relies on beta-glucan moieties within the HDM extract, as evidenced by the ability of other beta-glucans to competitively inhibit its secretion and by the fact that disruption of these structures by treatment of HDM with beta-glucanase significantly reduces subsequent chemokine secretion.


CONCLUSIONS
Taken together, our results describe a novel mechanism for specific pattern recognition of HDM-derived beta-glucan moieties, which initiates allergic airway inflammation and, through recruitment of DCs, might link innate pattern recognition at the airway surface with adaptive immune responses.
Nathan
Amy T
AT
Division of Neonatology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. Amy.Nathan@cchmc.org
Peterson
Elizabeth A
EA
Chakir
Jamila
J
Wills-Karp
Marsha
M
D000328:Adult; D000485:Allergens / Q000276:immunology*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology* / Q000494:pharmacology; D060829:Arthropod Proteins; D002460:Cell Line; D002478:Cells, Cultured; D054418:Chemokine CCL20 / Q000096:biosynthesis / Q000187:drug effects / Q000276:immunology*; D003546:Cysteine Endopeptidases; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D047908:Intracellular Signaling Peptides and Proteins / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010447:Peptide Hydrolases / Q000276:immunology / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D039981:Pyroglyphidae / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology; D000072377:Syk Kinase; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism; D047071:beta-Glucans / Q000276:immunology* / Q000378:metabolism
D000485:Allergens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; C108355:CCL20 protein, human; D054418:Chemokine CCL20; D047908:Intracellular Signaling Peptides and Proteins; D013267:Stilbenes; D051193:Toll-Like Receptors; D047071:beta-Glucans; C041525:3,3',4,5'-tetrahydroxystilbene; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1