Extracellular eosinophilic traps in association with Staphylococcus aureus at the site of epithelial barrier defects in patients with severe airway inflammation
Extracellular eosinophilic traps in association with Staphylococcus aureus at the site of epithelial barrier defects in patients with severe airway inflammation
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DOI：
10.1016/j.jaci.2017.01.019
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发表时间：
2017-06-01
影响因子：
14.2
通讯作者：
Bachert, Claus
中科院分区：
文献类型：
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作者：
Gevaert, Elien;Zhang, Nan;Bachert, Claus
背景：慢性鼻窦炎伴鼻息肉以T（H）2偏嗜酸性炎症为特征。嗜酸性粒细胞已被证明在类似的病理条件下产生所谓的细胞外嗜酸性粒细胞陷阱（EET）。目的：我们的目的是调查EET形成和金黄色葡萄球菌（一种经常定植在上呼吸道的生物体）在疾病的人体粘膜部位的存在之间的可能联系。方法：分别使用免疫荧光染色和PNA-Fish测定法研究组织切片中是否存在Escherichia coli和金黄色葡萄球菌。使用离体人粘膜疾病组织模型人工感染金黄色葡萄球菌。应用免疫组化、Luminex Multiplex检测、ELISA、PCR和免疫印迹分析细胞标志物，并将其与Escherichia coli的存在联系起来。结果：患者鼻息肉组织中约8.8% ± 4.8%的浸润性嗜酸性粒细胞显示Escherichia coli。Escherichia的形成与IL-5（P <0.05）和骨膜蛋白（P <0.05）组织水平的增加以及金黄色葡萄球菌的定植（P <0.05）相关。通过使用离体人粘膜疾病组织模型，暴露于金黄色葡萄球菌而非表皮葡萄球菌时诱导EET形成（4.2 +/-0.9倍）。嗜酸性粒细胞向金黄色葡萄球菌迁移（P <0.01），并在粘膜组织内外捕获细菌。结论：嗜酸性粒细胞可能被金黄色葡萄球菌和其他微生物特异性地募集，并在气道上皮损伤部位形成EET，以保护慢性鼻窦炎鼻息肉患者的宿主免受感染。
Background: Chronic rhinosinusitis with nasal polyps is characterized by T(H)2-biased eosinophilic inflammation. Eosinophils have been shown to generate so-called extracellular eosinophilic traps (EETs) under similar pathologic conditions.Objective: Our aim was to investigate a possible link between EET formation and the presence of Staphylococcus aureus, an organism frequently colonizing the upper airways, at the human mucosal site of the disease.Methods: Tissue slides were investigated for the presence of EETs and S aureus by using immunofluorescent staining and the PNA-Fish assay, respectively. An ex vivo human mucosal disease tissue model was used for artificial infection with S aureus. Cell markers were analyzed by using immunohistochemistry, the Luminex Multiplex assay, ELISA, PCR, and immunoblotting and linked to the presence of EETs.Results: About 8.8% +/- 4.8% of the infiltrating eosinophils exhibited EETs in patients' nasal polyp tissues. Formation of EETs was associated with increased IL-5 (P < .05) and periostin (P < .05) tissue levels and colonization with S aureus (P < .05). By using an ex vivo human mucosal disease tissue model, EET formation was induced (4.2 +/- 0.9-fold) on exposure to S aureus but not Staphylococcus epidermidis. Eosinophils were shown to migrate (P < .01) toward S aureus and entrap the bacteria both inside and outside the mucosal tissue. Blocking NAPDH oxidase activity led to a complete inhibition (P < .05) of EET formation by S aureus.Conclusion: Eosinophils are likely to be specifically recruited to S aureus and possibly other microorganisms and form EETs at sites of airway epithelial damage to protect the host from infections in patients with chronic rhinosinusitis with nasal polyps.