Oral and nasal sensitization promote distinct immune responses and lung reactivity in a mouse model of peanut allergy

Oral and nasal sensitization promote distinct immune responses and lung reactivity in a mouse model of peanut allergy
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DOI:
10.1016/s0002-9440(10)61246-1
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发表时间:
2005-12-01
影响因子:
6
通讯作者:
Boyaka, PN
Boyaka, PN
中科院分区:
医学2区
文献类型:
--
作者:
Fischer, R;McGhee, JR;Boyaka, PN

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尽管最初接触胃肠道和鼻腔变应原的部位在结构和功能上存在差异,但很少有动物模型研究粘膜致敏途径对宿主对食物或环境抗原的反应性的影响。为了建立小鼠过敏模型,我们比较了口服和鼻腔花生致敏的途径。在霍乱毒素佐剂存在的情况下,给予花生蛋白致敏小鼠。检测抗体和细胞因子反应,以及对花生或无关抗原鼻腔攻击的呼吸道反应性。与鼻腔致敏相比,口服致敏可提高IgE水平,但降低免疫球蛋白G反应。经口服和鼻腔致敏的小鼠对鼻腔花生刺激均出现呼吸道高反应性。花生刺激还诱导了口服致敏小鼠的肺嗜酸性粒细胞增多和2型辅助T细胞型细胞因子。相反,在鼻致敏小鼠中,花生刺激促进了中性粒细胞和肺MAC-1(+)I-A(B)(低)细胞和炎性细胞因子水平的升高。此外,鼻腔致敏,而不是口服致敏,促进了对无关抗原的肺部炎症反应。综上所述,口服和鼻腔花生致敏都能启动小鼠的呼吸道高反应性,但最初的粘膜致敏途径会影响花生和无关过敏原引起的肺炎症反应的性质。
Despite structural and functional differences between the initial sites of contact with allergens in the gastrointestinal and nasal tracts, few animal models have examined the influence of the mucosal routes of sensitization on host reactivity to food or environmental antigens. We compared the oral and nasal routes of peanut sensitization for the development of a mouse model of allergy. Mice were sensitized by administration of peanut proteins in the presence of cholera toxin as adjuvant. Antibody and cytokine responses were characterized, as well as airway reactivity to nasal challenge with peanut or unrelated antigens. Oral sensitization promoted higher levels of IgE, but lower IgG responses, than nasal sensitization. Both orally and nasally sensitized mice experienced airway hyperreactivity on nasal peanut challenge. The peanut challenge also induced lung eosinophilia and type 2 helper T-cell-type cytokines in orally sensitized mice. In contrast, peanut challenge in nasally sensitized mice promoted neutrophilia and higher levels of lung MAC-1(+) I-A(b) (low) cells and inflammatory cytokines. In addition, nasal but not oral, sensitization promoted lung inflammatory responses to unrelated antigens. In summary, both oral and nasal peanut sensitization prime mice for airway hyperreactivity, but the initial mucosal route of sensitization influences the nature of lung inflammatory responses to peanut and unrelated allergens.