Staphylococcus aureus enterotoxin B disrupts nasal epithelial barrier integrity
Staphylococcus aureus enterotoxin B disrupts nasal epithelial barrier integrity
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DOI：
10.1111/cea.13760
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发表时间：
2020-10-31
影响因子：
6.1
通讯作者：
Steelant, Brecht
中科院分区：
文献类型：
--
作者：
Martens, Katleen;Seys, Sven F.;Steelant, Brecht
金黄色葡萄球菌定植和肠毒素B（SE B）的释放与严重慢性鼻窦炎伴鼻息肉（CRSwNP）有关。目的探讨SEB对鼻黏膜上皮屏障功能的影响方法将SEB分别应用于CRSwNP患者和健康对照的鼻黏膜上皮细胞和鼻息肉的气液界面（air-liquid interface，ALI）培养中，观察SEB对鼻黏膜上皮屏障功能的影响。评价上皮细胞完整性和紧密连接表达。用TLR 2单克隆抗体在体外和tlr 2（-/-）基因敲除小鼠体内研究了TLR 2激活的参与。结果SEB应用于ALI培养的息肉上皮细胞，通过减少闭合蛋白和闭合小带（ZO）-1蛋白的表达，降低上皮细胞的完整性。拮抗TLR 2防止SEB诱导的屏障破坏。SEB应用于对照小鼠的鼻中增加了粘膜渗透性并降低了occludin和ZO-1的mRNA表达，而tlr 2（-/-）小鼠的粘膜完整性和紧密连接表达保持不变。此外，体外SEB刺激导致鼻息肉上皮细胞产生IL-6和IL-8，这是由TLR 2抑制的。结论与临床相关性SEB通过触发CRSwNP中的TLR 2损伤鼻息肉上皮细胞的完整性。我们的研究结果表明，SEB可能是疾病恶化的驱动因素，而不是CRSwNP上皮缺陷的因果因素。干扰TLR 2触发可能提供一种避免S.金黄色葡萄球菌对CRSwNP中炎症的影响。
Background Staphylococcus aureus colonization and release of enterotoxin B (SEB) has been associated with severe chronic rhinosinusitis with nasal polyps (CRSwNP). The pathogenic mechanism of SEB on epithelial barriers, however, is largely unexplored.Objective We investigated the effect of SEB on nasal epithelial barrier function.Methods SEB was apically administered to air-liquid interface (ALI) cultures of primary polyp and nasal epithelial cells of CRSwNP patients and healthy controls, respectively. Epithelial cell integrity and tight junction expression were evaluated. The involvement of Toll-like receptor 2 (TLR2) activation was studied in vitro with TLR2 monoclonal antibodies and in vivo in tlr2(-/-) knockout mice.Results SEB applied to ALI cultures of polyp epithelial cells decreased epithelial cell integrity by diminishing occludin and zonula occludens (ZO)-1 protein expression. Antagonizing TLR2 prevented SEB-induced barrier disruption. SEB applied in the nose of control mice increased mucosal permeability and decreased mRNA expression of occludin and ZO-1, whereas mucosal integrity and tight junction expression remained unaltered in tlr2(-/-) mice. Furthermore, in vitro SEB stimulation resulted in epithelial production of IL-6 and IL-8, which was prevented by TLR2 antagonization.Conclusion & Clinical relevance SEB damages nasal polyp epithelial cell integrity by triggering TLR2 in CRSwNP. Our results suggest that SEB might represent a driving factor of disease exacerbation, rather than a causal factor for epithelial defects in CRSwNP. Interfering with TLR2 triggering might provide a way to avoid the pathophysiological consequences of S. aureus on inflammation in CRSwNP.