title: Induction of the specific allergic immune response is independent of proteases from the fungus Alternaria alternata.
abstract: We have analyzed the importance of proteases for the induction of allergic responses against the mold Alternaria alternata. Responses induced in vivo with untreated or heat treated (protease inactivated) extracts were compared in BALB/c, C57BL/6, TLR4 KO, and MyD88 KO mice. In BALB/c mice, both extracts induced similar lung inflammation, upregulation of inflammatory mediators, Th2 cytokines, and Alternaria-specific antibodies. However heat inactivation abrogated polyclonal IgE production. Similar results were obtained in C57BL/6 albeit lung expression of some Th2 mediators was decreased in mice stimulated with the heat-treated extract. Treatment of the extract with protease inhibitors did not affect the induction of the allergic response either, except again for the polyclonal IgE response. Th2 responses and lung inflammation were readily induced in TLR4 knockout mice. In contrast, lung inflammation, Th2 responses, cytokine productions, and antibody synthesis were strongly suppressed in MyD88-deficient mice. Early lung IL-33 and IL-1-α expression were also suppressed. In conclusion, albeit some heat labile proteases are required for the stimulation of the polyclonal IgE secretion, fungal proteases, and TLR4 signaling are not required while MyD88 is essential for triggering the systemic immune response and for the development of lung allergic inflammation in response to Alternaria extracts.
authors: Program Allergology, WIV-ISP (site Ukkel), Brussels, Belgium. odenis@wiv-isp.be
authors: Olivier
authors: O
authors: Denis
authors: Muriel
authors: M
authors: Vincent
authors: Xavier
authors: X
authors: Havaux
authors: Sofie
authors: S
authors: De Prins
authors: Greta
authors: G
authors: Treutens
authors: Kris
authors: K
authors: Huygen
mesh_terms: D000528:Alternaria / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004789:Enzyme Activation; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D016207:Cytokines; D000939:Epitopes; D053594:Myeloid Differentiation Factor 88; D051197:Toll-Like Receptor 4; D010447:Peptide Hydrolases