Sputum from People with Cystic Fibrosis Reduces the Killing of Methicillin-Resistant Staphylococcus aureus by Neutrophils and Diminishes Phagosomal Production of Reactive Oxygen Species.
Sputum from People with Cystic Fibrosis Reduces the Killing of Methicillin-Resistant Staphylococcus aureus by Neutrophils and Diminishes Phagosomal Production of Reactive Oxygen Species.
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DOI：
10.3390/pathogens12091148
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发表时间：
2023-09-09
期刊：
影响因子：
--
通讯作者：
Rada B
中科院分区：
文献类型：
--
作者：
Fantone KM;Goldberg JB;Stecenko AA;Rada B
囊性纤维化 (CF) 气道疾病的特征是慢性多种微生物感染和中性粒细胞 (PMN) 浸润。金黄色葡萄球菌是 CF 中最常见的呼吸道病原体。特别是，耐甲氧西林金黄色葡萄球菌（MRSA）由于与肺部疾病和抗生素耐药性增加相关，给 CF 带来了巨大的临床负担。在 CF 中，PMN 无法杀死和清除 MRSA。其原因很大程度上仍不清楚。我们的研究发现，CF PMN 与健康 PMN 一样能够杀死 MRSA。然而，我们发现 CF 痰会显着削弱人类 PMN 杀死 CF MRSA 分离株的能力。在没有 CF 痰的情况下，PMN 通过吞噬作用介导的细胞内机制杀死 MRSA，而不是通过 NET 形成的细胞外机制。 CF 痰不影响健康或 CF PMN 对 MRSA 的吞噬作用。我们的结果表明，CF 痰暴露会损害 MRSA 吞噬 PMN 中活性氧 (ROS) 的吞噬体水平。虽然在 CF 痰暴露后，MRSA 与主要颗粒标记物、髓过氧化物酶和组织蛋白酶 D 的吞噬体共定位显着减少，但第三种嗜天青颗粒标记物、中性粒细胞弹性蛋白酶的吞噬体共定位不受影响。这表明 CF 痰不会损害初级颗粒与吞噬体的融合，而是通过另一种可能更具体的机制降低吞噬体 ROS 水平。总的来说，我们认为气道环境是限制中性粒细胞针对 MRSA 的 CF 氧化杀菌活性的重要因素。这些结果提供了 CF 肺中复杂的宿主-病原体相互作用的新细节。
Cystic fibrosis (CF) airway disease is characterized by chronic polymicrobial infections and an infiltration of neutrophils (PMNs). Staphylococcus aureus has been the most prevalent respiratory pathogen in CF. In particular, methicillin-resistant S. aureus (MRSA) represents a huge clinical burden in CF due to its association with lung disease and increased resistance to antibiotics. In CF, PMNs are unable to kill and clear MRSA. The reason for this remains largely unknown. Our study found that CF PMNs are as equally capable of killing MRSA as healthy PMNs. We show that the CF sputum, however, significantly impairs the ability of human PMNs to kill CF MRSA isolates. In the absence of CF sputum, PMNs kill MRSA via intracellular mechanisms mediated by phagocytosis, rather than extracellular mechanisms via NET formation. CF sputum does not affect the phagocytosis of MRSA via healthy or CF PMNs. Our results demonstrate that CF sputum exposure impairs phagosomal levels of reactive oxygen species (ROS) in MRSA-phagocytosing PMNs. While phagosomal co-localizations of MRSA with primary granule markers, myeloperoxidase and cathepsin D, were significantly reduced upon CF sputum exposure, that of a third azurophilic granule marker, neutrophil elastase, remained unaffected. This suggests that CF sputum does not compromise the fusion of primary granules with phagosomes but diminishes phagosomal ROS levels via another, likely more specific, mechanism. Overall, we identified the airway environment as an important factor that restricts neutrophils’ oxidative microbicidal activities in CF against MRSA. These results deliver new details of the complex host–pathogen interactions present in the CF lung.
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影响因子：
7.3
作者：
Hayes E;Murphy MP;Pohl K;Browne N;McQuillan K;Saw LE;Foley C;Gargoum F;McElvaney OJ;Hawkins P;Gunaratnam C;McElvaney NG;Reeves EP
通讯作者：
Reeves EP
影响因子：
5.3
作者：
Dwyer M;Shan Q;D'Ortona S;Maurer R;Mitchell R;Olesen H;Thiel S;Huebner J;Gadjeva M
通讯作者：
Gadjeva M
影响因子：
3.1
作者：
Ahlgren HG;Benedetti A;Landry JS;Bernier J;Matouk E;Radzioch D;Lands LC;Rousseau S;Nguyen D
通讯作者：
Nguyen D
影响因子：
3.1
作者：
Akil, Nour;Muhlebach, Marianne S.
通讯作者：
Muhlebach, Marianne S.
影响因子：
3.7
作者：
De Jong, Nienke W. M.;Van Kessel, Kok P. M.;Van Strijp, Jos A. G.
通讯作者：
Van Strijp, Jos A. G.