Staphylococcal protein A-formulated immune complexes suppress enterotoxin-induced cellular responses in nasal polyps
Staphylococcal protein A-formulated immune complexes suppress enterotoxin-induced cellular responses in nasal polyps
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DOI：
10.1016/j.jaci.2014.10.058
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发表时间：
2015-08-01
影响因子：
14.2
通讯作者：
Nishizaki, Kazunori
中科院分区：
文献类型：
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作者：
Okano, Mitsuhiro;Fujiwara, Tazuko;Nishizaki, Kazunori
背景：近年来的研究表明，金黄色葡萄球菌及其成分参与嗜酸性气道疾病的发病机制，如慢性鼻窦炎伴鼻息肉。目的：我们试图确定来自金黄色葡萄球菌的葡萄球菌蛋白A （SpA）是否调节鼻息肉的细胞反应，特别是当它与免疫复合物（ic）中的免疫球蛋白偶联时。方法：用SpA体外培养分散鼻息肉细胞（DNPCs）或外周血单核细胞，在IgG存在或不存在的情况下，检测上清液中IL-5、IL-13、ifn - γ、IL-17A和IL-10的水平。我们还检测了SpA暴露对葡萄球菌肠毒素b诱导的DNPCs在IgG、IgA和自体血清存在和不存在的情况下产生细胞因子的影响。结果：暴露于SpA诱导的DNPCs产生的IL-10、IL-13和IL-17A水平明显高于未暴露SpA的DNPCs，但IL-17A的增加幅度小于IL-10和IL-13。SpA诱导IL-10的产生主要来自粘附的DNPCs，且IgG的存在显著增强了IL-10的产生；在外周血单核细胞中也观察到类似的结果。用天然聚丙烯酰胺凝胶电泳证实SpA与IgG之间形成IC （SpA-IgG IC）。SpA- igg ic，但不是SpA单独，几乎完全抑制葡萄球菌肠毒素b诱导的DNPCs产生IL-5、IL-13、ifn - γ和IL-17A；在IgA或自体血清存在的情况下，用SpA处理的DNPCs也有类似的抑制作用。结论：本研究提示SpA可通过偶联免疫球蛋白调节慢性鼻窦炎伴鼻息肉患者肠毒素性炎症的发病机制。
Background: Recent studies have revealed that Staphylococcus aureus and its components participate in the pathogenesis of eosinophilic airway diseases, such as chronic rhinosinusitis with nasal polyps.Objective: We sought to determine whether staphylococcal protein A (SpA) from S aureus regulated cellular responses in nasal polyps, especially when coupled to immunoglobulins in immune complexes (ICs).Methods: Dispersed nasal polyp cells (DNPCs) or peripheral blood monocytes were cultured in vitro with SpA in the presence or absence of IgG, and IL-5, IL-13, IFN-gamma, IL-17A, and IL-10 levels were measured in the supernatants. The effect of SpA exposure on staphylococcal enterotoxin B-induced cytokine production by DNPCs in the presence and absence of IgG, IgA, and autologous serum was also examined.Results: Exposure to SpA induced DNPCs to produce significantly higher IL-10, IL-13, and IL-17A levels than DNPCs without SpA, although the magnitude of the IL-17A increase was less than that of IL-10 and IL-13. SpA induced IL-10 production mainly from adherent DNPCs, and this was significantly enhanced in the presence of IgG; similar results were observed in peripheral blood monocytes. IC formation between SpA and IgG (SpA-IgG ICs) was confirmed by using native polyacrylamide gel electrophoresis. SpA-IgG ICs, but not SpA alone, almost completely suppressed staphylococcal enterotoxin B-induced IL-5, IL-13, IFN-gamma, and IL-17A production by DNPCs; similar inhibition was observed in DNPCs treated with SpA in the presence of either IgA or autologous serum.Conclusions: Our results suggest that SpA can regulate the pathogenesis of enterotoxin-induced inflammation in patients with chronic rhinosinusitis with nasal polyps through coupling to immunoglobulins.