Staphylococcal protein A modulates inflammation by inducing interferon signaling in human nasal epithelial cells.
Staphylococcal protein A modulates inflammation by inducing interferon signaling in human nasal epithelial cells.
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DOI：
10.1007/s00011-022-01656-1
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发表时间：
2023-02
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金黄色葡萄球菌（金黄色葡萄球菌）是人类呼吸道感染的主要原因之一。葡萄球菌蛋白A （Staphylococcal protein A, SpA）在金黄色葡萄球菌（S. aureus）细菌膜上表达并在环境中释放，其对人鼻上皮细胞（HNECs）的作用尚未完全阐明。本研究通过干扰素γ受体1(IFNGR1)/磷酸化Janus激酶2 （p-JAK2）通路检测SpA在慢性鼻窦炎患者金黄色葡萄球菌中的表达，探讨SpA对HNECs炎症的影响。采用RNA谱分析方法研究金黄色葡萄球菌慢性鼻窦炎（CRS）小鼠模型的炎症激活。采用ELISA法测定金黄色葡萄球菌临床分离株的SpA释放量。采用乳酸脱氢酶法和流式细胞术评估金黄色葡萄球菌临床分离株纯化SpA和富集SpA条件培养基对HNECs细胞毒性、细胞凋亡和炎性细胞因子释放的影响。采用qPCR、免疫荧光和western blot检测HNECs中SpA依赖性IFNGR1和p-JAK2的表达。49个基因在金黄色葡萄球菌CRS小鼠中被显著诱导，表明干扰素信号被激活。慢性鼻鼻窦炎伴鼻息肉（CRSwNP）患者的金黄色葡萄球菌临床分离株的SpA释放量明显较高。纯化的SpA显著提高了HNECs中IFNGR1 mRNA和蛋白的表达。SpA诱导细胞毒性作用，并以IFNGR1依赖的方式诱导白细胞介素6 （IL-6）和IL-8的释放。SpA通过激活IFNGR1-JAK-2通路诱导干扰素信号传导，这为了解金黄色葡萄球菌SpA如何影响上呼吸道炎症过程提供了线索。在线版本包含补充材料，下载地址为10.1007/s00011-022-01656-1。
Staphylococcus aureus (S. aureus) is one of the leading causes of human respiratory tract infections. The function of Staphylococcal protein A (SpA), expressed on the S. aureus bacterial membrane and released in the environment, on human nasal epithelial cells (HNECs) have not been fully elucidated. In this study, we tested the SpA expression in S. aureus from chronic rhinosinusitis patients and investigated the effects of SpA on HNECs inflammation through Interferon Gamma Receptor 1(IFNGR1)/phosphorylated Janus Kinase 2 (p-JAK2) pathway. RNA profiling was performed to investigate inflammatory activation in a S. aureus chronic rhinosinusitis (CRS) mouse model. SpA release by S. aureus clinical isolates was determined using ELISA. The effect of purified SpA and SpA enriched conditioned media from S. aureus clinical isolates on HNECs cytotoxicity, apoptosis and release of inflammatory cytokines was evaluated using lactate dehydrogenase assays, and flow cytometry. SpA dependent IFNGR1 and p-JAK2 expression were assessed by qPCR, immunofluorescence and western blot in HNECs. 49 genes were significantly induced in S. aureus CRS mice indicative of activation of interferon signaling. SpA release was significantly higher in S. aureus clinical isolates from chronic rhinosinusitis with nasal polyps (CRSwNP) patients. Purified SpA significantly increased IFNGR1 mRNA and protein expression in HNECs. SpA induced cytotoxic effects and induced the release of Interleukin-6 (IL-6) and IL-8 in an IFNGR1 dependent way. SpA induces interferon signaling through activation of the IFNGR1-JAK-2 pathway, which provides an understanding of how S. aureus SpA affects the inflammatory process in the upper airways. The online version contains supplementary material available at 10.1007/s00011-022-01656-1.
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影响因子：
7.3
作者：
Jang YJ;Lim JY;Kim S;Lee Y;Kweon MN;Kim JH
通讯作者：
Kim JH
影响因子：
6.4
作者：
Falugi F;Kim HK;Missiakas DM;Schneewind O
通讯作者：
Schneewind O
DOI：
10.1126/science.1176667
发表时间：
2009-08-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fischbach MA;Walsh CT
通讯作者：
Walsh CT
影响因子：
6.3
作者：
Bassetti, Matteo;Righi, Elda;Carnelutti, Alessia
通讯作者：
Carnelutti, Alessia
影响因子：
7.2
作者：
Fokkens, Wytske J.;Lund, Valerie J.;Zwetsloot, Casper P.
通讯作者：
Zwetsloot, Casper P.