Intestinal helminths protect in a murine model of asthma
Intestinal helminths protect in a murine model of asthma
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DOI：
10.4049/jimmunol.177.3.1628
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发表时间：
2006-08-01
影响因子：
4.4
通讯作者：
Kline, Joel N.
中科院分区：
文献类型：
--
作者：
Kitagaki, Kunihiko;Businga, Thomas R.;Kline, Joel N.
不发达国家相对不受全球哮喘流行的影响；卫生学假说表明，这是因为通过增加接触病原体及其产品来抑制Th2介导的炎症。尽管微生物暴露可以促进抑制Th2的Th1反应，但即使是扭曲Th2的感染，如蠕虫，似乎也会抑制特应性，这为这些观察到的结果提出了另一种解释。为了研究蠕虫诱导的调节反应是否可以对抗过敏性炎症，我们检查了蠕虫感染对特应性哮喘小鼠模型的影响。我们选择了一种胃肠道线虫多回螺旋线虫作为实验蠕虫，这种蠕虫在其生活史中不进入肺部。我们发现，多回毛虫感染以IL-10依赖的方式抑制变应原诱导的气道嗜酸粒细胞增多症、支气管高反应性和体外变应原召回Th2反应；然而，蠕虫感染增加了总IgE和OVA特异性IgE。最后，蠕虫感染的小鼠可以抵抗过继转移OVA刺激的CD4(+)细胞引起的嗜酸性炎症，而从蠕虫感染/OVA暴露的小鼠中转移细胞可以抑制OVA诱导的嗜酸性炎症，这表明调节细胞的作用。线虫感染/卵清蛋白暴露组小鼠胸腺淋巴结中的CD4(+)CD25(+)Foxp3(+)细胞明显增多。蠕虫的定植似乎可以预防哮喘和特应性疾病；调节性细胞因子IL-10可能是一个关键角色。
Underdeveloped nations are relatively protected from the worldwide asthma epidemic; the hygiene hypothesis suggests this is due to suppression of Th2-mediated inflammation by increased exposure to pathogens and their products. Although microbial exposures can promote Th2-suppressing Th1 responses, even Th2-skewing infections, such as helminths, appear to suppress atopy, suggesting an alternate explanation for these observations. To investigate whether induction of regulatory responses by helminths may counter allergic inflammation, we examined the effects of helminth infection in a murine model of atopic asthma. We chose Heligosomoides polygyrus, a gastrointestinal nematode, as the experimental helminth; this worm does not enter the lung in its life cycle. We found that H. polygyrus infection suppressed allergen-induced airway eosinophilia, bronchial hyperreactivity, and in vitro allergen-recall Th2 responses in an IL-10-dependent manner; total and OVA-specific IgE, however, were increased by worm infection. Finally, helminth-infected mice were protected against eosinophilic inflammation induced by adoptive transfer of OVA-stimulated CD4(+) cells, and transfer of cells from helminth-infected/OVA-exposed mice suppressed OVA-induced eosinophilic inflammation, suggesting a role for regulatory cells. Increased CD4(+)CD25(+)Foxp3(+) cells were found in thoracic lymph nodes of helminth-infected/OVA-exposed mice. Helminthic colonization appears to protect against asthma and atopic disorders; the regulatory cytokine, IL-10, may be a critical player.