Basophil-mediated protection against gastrointestinal helminths requires IgE-induced cytokine secretion
Basophil-mediated protection against gastrointestinal helminths requires IgE-induced cytokine secretion
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DOI：
10.1073/pnas.1412663111
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发表时间：
2014-12-02
影响因子：
11.1
通讯作者：
Voehringer, David
中科院分区：
文献类型：
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作者：
Schwartz, Christian;Turqueti-Neves, Adriana;Voehringer, David
嗜碱性粒细胞通过胃肠道蠕虫和扁虱来协调对再次感染的保护，但潜在的机制仍然难以捉摸。我们研究了Fc受体在嗜碱性粒细胞上的作用，抗体亚型IgG1和IgE，以及嗜碱性粒细胞衍生的IL-4/IL-13在攻击感染多回螺杆菌和巴西拟青霉时的作用。使用混合骨髓嵌合体，我们发现激活嗜碱性粒细胞上的Fc受体是保护性免疫所必需的，但不是调节嗜碱性粒细胞动态平衡所必需的。此外，在IgE缺陷的小鼠中，快速驱虫受到损害，但在IgG1缺陷的小鼠中则不受影响。嗜碱性细胞促进其他效应细胞在小肠中的募集，并诱导抗蠕虫蛋白抵抗素样分子β和粘蛋白5AC的表达。嗜碱性粒细胞中IL-4/IL-13的选择性缺失会导致蠕虫排出障碍。综上所述，我们的结果表明，IgE介导的嗜碱性粒细胞活化和嗜碱性粒细胞来源的IL-4/IL-13的释放是抗蠕虫保护性免疫的关键步骤。因此，开发有效的蠕虫疫苗应考虑增强免疫系统的IL-4/IgE/嗜碱性粒细胞轴。
Basophils orchestrate protection against reinfections with gastrointestinal helminths and ticks, but the underlying mechanisms remain elusive. We investigated the role of Fc receptors on basophils, the antibody isotypes IgG1 and IgE, and basophil-derived IL-4/IL-13 during challenge infections with Heligmosomoides polygyrus and Nippostrongylus brasiliensis. Using mixed bone marrow chimeras, we found that activating Fc receptors on basophils were required for protective immunity but not for regulation of basophil homeostasis. Furthermore, rapid worm expulsion was impaired in IgE-deficient but not in IgG1-deficient mice. Basophils promoted the recruitment of other effector cells into the small intestine and induced expression of the antihelminthic proteins resistin-like molecule beta and mucin 5ac. Selective deletion of IL-4/IL-13 in basophils resulted in impaired worm expulsion. Collectively, our results indicate that IgE-mediated activation of basophils and the release of basophil-derived IL-4/IL-13 are critical steps in protective immunity against helminths. Therefore, development of effective vaccines against helminths should consider boosting the IL-4/IgE/basophil axis of the immune system.