Induction of the specific allergic immune response is independent of proteases from the fungus Alternaria alternata
Induction of the specific allergic immune response is independent of proteases from the fungus Alternaria alternata
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DOI：
10.1002/eji.201242630
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发表时间：
2013-04-01
影响因子：
5.4
通讯作者：
Huygen, Kris
中科院分区：
文献类型：
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作者：
Denis, Olivier;Vincent, Muriel;Huygen, Kris
我们已经分析了蛋白酶对霉菌链格孢菌过敏反应的诱导的重要性。在BALB/c、C57 BL/6、TLR 4 KO和MyD 88 KO小鼠中比较了未处理或热处理（蛋白酶灭活）提取物在体内诱导的反应。在BALB/c小鼠中，两种提取物诱导相似的肺部炎症，炎症介质，Th 2细胞因子和链格孢特异性抗体的上调。然而，热灭活废除了多克隆IgE的生产。在C57 BL/6中获得了类似的结果，尽管在用热处理提取物刺激的小鼠中一些Th 2介质的肺表达降低。用蛋白酶抑制剂处理提取物也不影响过敏反应的诱导，除了多克隆IgE反应。在TLR 4敲除小鼠中容易诱导Th 2应答和肺部炎症。相比之下，MyD 88缺陷小鼠的肺部炎症、Th 2应答、细胞因子产生和抗体合成受到强烈抑制。早期肺IL-33和IL-1表达也受到抑制。总之，尽管需要一些热不稳定蛋白酶来刺激多克隆IgE分泌，但不需要真菌蛋白酶和TLR 4信号传导，而MyD 88对于触发全身免疫应答和响应于链格孢属提取物的肺变应性炎症的发展是必需的。
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- 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.