Staphylococcus aureus SaeR/S-Regulated Factors Decrease Monocyte-Derived Tumor Necrosis Factor-α to Reduce Neutrophil Bactericidal Activity.
Staphylococcus aureus SaeR/S-Regulated Factors Decrease Monocyte-Derived Tumor Necrosis Factor-α to Reduce Neutrophil Bactericidal Activity.
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金黄色葡萄球菌 SaeR/S 调节因子可减少单核细胞衍生的肿瘤坏死因子-α，从而降低中性粒细胞的杀菌活性。
DOI：
10.1093/infdis/jix652
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Voyich,JovankaM
中科院分区：
文献类型：
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作者：
Sward,EliW;Fones,ElizabethM;Spaan,RusselR;Pallister,KylerB;Haller,BrandonL;Guerra,FerminE;Zurek,OliwiaW;Nygaard,TylerK;Voyich,JovankaM
背景金黄色葡萄球菌逃避人类中性粒细胞杀伤的能力在疾病进展中起重要作用。在这项研究中，我们描述了一个有影响力的作用，为S。方法采用流式细胞术和TNF-α特异性酶联免疫吸附试验，我们鉴定了人血液和纯化的外周血单个核细胞（PBMC）与USA 300和一个同基因SaeR/S缺失突变体相互作用时TNF-α的主要细胞来源（美国300磅/秒）。USA 300和USA 300 β R/S暴露的PBMC的条件培养基的测定被用来调查启动对中性粒细胞杀菌活性。结果与USA 300 β R/S相比，USA 300 β R/S攻击后单核细胞TNF-α的产生显著减少。我们观察到，相对于未致敏的嗜中性粒细胞和用USA 300条件培养基致敏的嗜中性粒细胞，使用来自用USA 300 β R/S刺激的外周血单核细胞的条件培养基致敏嗜中性粒细胞显著增加了嗜中性粒细胞对USA 300的杀菌活性。增加的中性粒细胞杀菌活性与增强的活性氧产生相关，活性氧产生受TNF-α浓度升高的显著影响。金黄色葡萄球菌以阻碍嗜中性粒细胞引发和随后的杀菌活性。
BackgroundThe ability of Staphylococcus aureus to evade killing by human neutrophils significantly contributes to disease progression. In this study, we characterize an influential role for the S. aureus SaeR/S 2-component gene regulatory system in suppressing monocyte production of tumor necrosis factor alpha (TNF-α) to subsequently influence human neutrophil priming.MethodsUsing flow cytometry and TNF-α specific enzyme-linked immunosorbent assays we identify the primary cellular source of TNF-α in human blood and in purified peripheral blood mononuclear cells (PBMCs) during interaction with USA300 and an isogenic saeR/S deletion mutant (USA300∆saeR/S). Assays with conditioned media from USA300 and USA300∆saeR/S exposed PBMCs were used to investigate priming on neutrophil bactericidal activity.ResultsTNF-α production from monocytes was significantly reduced following challenge with USA300 compared to USA300∆saeR/S. We observed that priming of neutrophils using conditioned medium from peripheral blood mononuclear cells stimulated with USA300∆saeR/S significantly increased neutrophil bactericidal activity against USA300 relative to unprimed neutrophils and neutrophils primed with USA300 conditioned medium. The increased neutrophil bactericidal activity was associated with enhanced reactive oxygen species production that was significantly influenced by elevated TNF-α concentrations.ConclusionsOur findings identify an immune evasion strategy used by S. aureus to impede neutrophil priming and subsequent bactericidal activity.