Induction of the specific allergic immune response is independent of proteases from the fungus <i><scp>A</scp>lternaria alternata</i>

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, C 57 BL /6, TLR 4 KO , and M y D 88 KO mice. In BALB /c mice, both extracts induced similar lung inflammation, upregulation of inflammatory mediators, T h2 cytokines, and A lternaria ‐specific antibodies. However heat inactivation abrogated polyclonal I g E production. Similar results were obtained in C 57 BL /6 albeit lung expression of some T h2 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 I g E response. T h2 responses and lung inflammation were readily induced in TLR 4 knockout mice. In contrast, lung inflammation, T h2 responses, cytokine productions, and antibody synthesis were strongly suppressed in M y D 88‐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 I g E secretion, fungal proteases, and TLR 4 signaling are not required while M y D 88 is essential for triggering the systemic immune response and for the development of lung allergic inflammation in response to A lternaria extracts.