Upper Airways Research Laboratory, Faculty of Medicine, Ghent University, Ghent, Belgium.
Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium.
J Allergy Clin Immunol. 2017 Jun;139(6):1849-1860.e6. doi: 10.1016/j.jaci.2017.01.019. Epub 2017 Feb 17.
Chronic rhinosinusitis with nasal polyps is characterized by T2-biased eosinophilic inflammation. Eosinophils have been shown to generate so-called extracellular eosinophilic traps (EETs) under similar pathologic conditions.
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.
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.
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.
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.
伴有鼻息肉的慢性鼻-鼻窦炎的特征是 T2 偏向性嗜酸性粒细胞炎症。已经表明，在类似的病理条件下，嗜酸性粒细胞会产生所谓的细胞外嗜酸性粒细胞陷阱（EETs）。
我们旨在研究 EET 形成与金黄色葡萄球菌（一种经常定植在上呼吸道的生物体）在疾病的人类黏膜部位存在之间可能存在的联系。
通过免疫荧光染色和 PNA-Fish 检测分别研究组织切片中 EETs 和金黄色葡萄球菌的存在。使用体外人黏膜疾病组织模型进行金黄色葡萄球菌的人工感染。通过免疫组织化学、Luminex 多重分析、ELISA、PCR 和免疫印迹分析细胞标志物，并将其与 EETs 的存在联系起来。
在患者鼻息肉组织中，约 8.8%±4.8%的浸润嗜酸性粒细胞表现出 EETs。EETs 的形成与 IL-5（P<.05）和periostin（P<.05）组织水平的增加以及金黄色葡萄球菌的定植（P<.05）相关。通过使用体外人黏膜疾病组织模型，金黄色葡萄球菌暴露可诱导 EET 形成（4.2±0.9 倍），但表皮葡萄球菌不能。嗜酸性粒细胞被证明会向金黄色葡萄球菌迁移（P<.01），并在黏膜组织内外捕获细菌。阻断 NADPH 氧化酶活性可完全抑制金黄色葡萄球菌诱导的 EET 形成（P<.05）。
嗜酸性粒细胞可能被特异性招募到金黄色葡萄球菌和其他可能的微生物，并在气道上皮损伤部位形成 EETs，以保护患有伴有鼻息肉的慢性鼻-鼻窦炎的宿主免受感染。
