Impaired respiratory burst contributes to infections in PKCδ-deficient patients.
Impaired respiratory burst contributes to infections in PKCδ-deficient patients.
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DOI：
10.1084/jem.20210501
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发表时间：
2021-09-06
期刊：
影响因子：
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通讯作者：
Bustamante J
中科院分区：
文献类型：
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作者：
Neehus AL;Moriya K;Nieto-Patlán A;Le Voyer T;Lévy R;Özen A;Karakoc-Aydiner E;Baris S;Yildiran A;Altundag E;Roynard M;Haake K;Migaud M;Dorgham K;Gorochov G;Abel L;Lachmann N;Dogu F;Haskologlu S;İnce E;El-Benna J;Uzel G;Kiykim A;Boztug K;Roderick MR;Shahrooei M;Brogan PA;Abolhassani H;Hancioglu G;Parvaneh N;Belot A;Ikinciogullari A;Casanova JL;Puel A;Bustamante J
这项研究描述了 PKCδ 缺陷患者吞噬细胞产生的活性氧减少，这是遗传性人类 PKCδ 缺陷导致对传染病易感性的可能机制。常染色体隐性蛋白激酶 C δ (PKCδ) 缺陷患者患有儿童期发病的自身免疫性疾病，包括系统性红斑狼疮。他们还遭受反复感染，与慢性肉芽肿病 (CGD) 患者的感染重叠，慢性肉芽肿病是一种由吞噬细胞 NADPH 氧化酶缺陷和活性氧 (ROS) 生成缺乏引起的疾病。我们研究了 17 名 PKCδ 缺陷患者的国际队列，发现他们的 EBV-B 细胞和单核细胞来源的吞噬细胞仅产生少量 ROS，并且在 PMA 或调理金黄色葡萄球菌刺激后不会正常磷酸化 p40phox。此外，患者的循环吞噬细胞显示出异常低水平的 ROS 产生，并且中性粒细胞胞外陷阱的形成显着减少，这一切都表明 PKCδ 在 NADPH 氧化酶复合物的激活中发挥着作用。因此，我们的研究结果表明，PKCδ 缺乏的患者在各种骨髓亚群中的 NADPH 氧化酶活性受损，这可能导致其 CGD 样感染表型。
This study describes decreased production of reactive oxygen species by phagocytes of PKCδ-deficient patients as a possible mechanism by which inherited human PKCδ deficiency contributes to susceptibility to infectious diseases. Patients with autosomal recessive protein kinase C δ (PKCδ) deficiency suffer from childhood-onset autoimmunity, including systemic lupus erythematosus. They also suffer from recurrent infections that overlap with those seen in patients with chronic granulomatous disease (CGD), a disease caused by defects of the phagocyte NADPH oxidase and a lack of reactive oxygen species (ROS) production. We studied an international cohort of 17 PKCδ-deficient patients and found that their EBV-B cells and monocyte-derived phagocytes produced only small amounts of ROS and did not phosphorylate p40phox normally after PMA or opsonized Staphylococcus aureus stimulation. Moreover, the patients’ circulating phagocytes displayed abnormally low levels of ROS production and markedly reduced neutrophil extracellular trap formation, altogether suggesting a role for PKCδ in activation of the NADPH oxidase complex. Our findings thus show that patients with PKCδ deficiency have impaired NADPH oxidase activity in various myeloid subsets, which may contribute to their CGD-like infectious phenotype.