1 Department of Otolaryngology Head and Neck Surgery, Beijing Institute of Otolaryngology, Beijing TongRen Hospital, Capital Medical University, Beijing, China.
2 Upper Airways Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium.
Am J Respir Crit Care Med. 2018 Aug 15;198(4):452-463. doi: 10.1164/rccm.201710-2112OC.
Chronic rhinosinusitis with nasal polyps is characterized by a T-helper cell type 2-skewed upper airway inflammation. Mucosal Staphylococcus aureus colonization is found in the majority of patients with nasal polyps. S. aureus is known to induce type 2 cytokine release via enterotoxins.
To investigate the impact of non-enterotoxin-producing S. aureus on type 2 cytokine release.
TSLP (thymic stromal lymphopoietin), IL-33, and type 2 cytokines were assessed in a human mucosal tissue model upon S. aureus infection.
S. aureus exposure increased the expression of IL-33, TSLP, IL-5, and IL-13 in nasal polyp tissue, accompanied by elevated expression levels of TSLP and IL-33 receptors, predominantly on CD3 T cells. S. aureus infection led to the release of TSLP, but not IL-33, IL-5, or IL-13, from healthy inferior turbinate tissue. In contrast, S. epidermidis did not induce any epithelial cell-derived cytokines in nasal polyp or healthy tissue. S. aureus infection also increased the release of IL-33 and TSLP in BEAS-2B epithelial cells, accompanied by activation of NF-κB (nuclear factor κB) pathways. Incubation with CU-CPT22, a specific Toll-like receptor 2 antagonist, significantly reduced the S. aureus-induced release of TSLP and IL-33, and the activity of the NF-κB signal in BEAS-2B cells.
This study demonstrates for the first time that S. aureus can directly induce epithelial cell-derived cytokine release via binding to Toll-like receptor 2, and may thereby propagate type 2 cytokine expression in nasal polyp tissue.
伴有鼻息肉的慢性鼻-鼻窦炎的特征在于 2 型辅助性 T 细胞（Th2 细胞）为主的气道炎症。大多数鼻息肉患者存在金黄色葡萄球菌（S. aureus）定植。金黄色葡萄球菌已知通过肠毒素诱导 2 型细胞因子释放。
研究非产肠毒素的金黄色葡萄球菌对 2 型细胞因子释放的影响。
在人黏膜组织模型中，检测金黄色葡萄球菌感染后 TSLP（胸腺基质淋巴细胞生成素）、IL-33 和 2 型细胞因子的变化。
金黄色葡萄球菌暴露增加了鼻息肉组织中 IL-33、TSLP、IL-5 和 IL-13 的表达，同时 TSLP 和 IL-33 受体的表达水平升高，主要在 CD3 T 细胞上。金黄色葡萄球菌感染导致健康下鼻甲组织释放 TSLP，但不释放 IL-33、IL-5 或 IL-13。相比之下，表皮葡萄球菌在鼻息肉或健康组织中均未诱导任何上皮细胞衍生的细胞因子。金黄色葡萄球菌感染还增加了 BEAS-2B 上皮细胞中 IL-33 和 TSLP 的释放，并伴有 NF-κB（核因子 κB）途径的激活。用 CU-CPT22（一种特异性 Toll 样受体 2 拮抗剂）孵育可显著减少金黄色葡萄球菌诱导的 TSLP 和 IL-33 释放以及 BEAS-2B 细胞中 NF-κB 信号的活性。
本研究首次证明金黄色葡萄球菌可通过与 Toll 样受体 2 结合直接诱导上皮细胞衍生细胞因子的释放，并可能由此在鼻息肉组织中促进 2 型细胞因子的表达。
