The inflammasome is a multiprotein complex that mediates caspase-1 activation with subsequent maturation of the proinflammatory cytokines IL-1β and IL-18. The NLRP3 inflammasome is known to be activated by Staphylococcus aureus, one of the leading causes of bacteremia worldwide. Inflammasome activation and regulation in response to bacterial infection have been found to be of importance for a balanced host immune response. However, inflammasome signaling in vivo in humans initiated by S. aureus is currently sparsely studied. This study therefore aimed to investigate NLRP3 inflammasome activity in 20 patients with S. aureus bacteremia (SAB), by repeated measurement during the first week of bacteremia, compared with controls. Caspase-1 activity was measured in monocytes and neutrophils by flow cytometry detecting FLICA (fluorescent-labeled inhibitor of caspase-1), while IL-1β and IL-18 was measured by Luminex and ELISA, respectively. As a measure of inflammasome priming, messenger RNA (mRNA) expression of NLRP3, CASP1 (procaspase-1), and IL1B (pro-IL-1β) was analyzed by quantitative PCR. We found induced caspase-1 activity in innate immune cells with subsequent release of IL-18 in patients during the acute phase of bacteremia, indicating activation of the inflammasome. There was substantial interindividual variation in caspase-1 activity between patients with SAB. We also found an altered inflammasome priming with low mRNA levels of NLRP3 accompanied by elevated mRNA levels of IL1B. This increased knowledge of the individual host immune response in SAB could provide support in the effort to optimize management and treatment of each individual patient.

中文翻译：

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金黄色葡萄球菌菌血症患者的Caspase-1炎性体活性。

炎性小体是一种多蛋白复合物，介导caspase-1的激活以及促炎性细胞因子IL-1β和IL-18的成熟。已知NLRP3炎性小体被金黄色葡萄球菌激活，金黄色葡萄球菌是全世界菌血症的主要原因之一。已经发现响应细菌感染的炎性体活化和调节对于平衡宿主免疫反应是重要的。然而，目前很少研究由金黄色葡萄球菌引发的人体内炎症小体信号传导。因此，本研究旨在通过与对照相比，在菌血症的第一周内进行重复测量，调查20例金黄色葡萄球菌菌血症（SAB）患者的NLRP3炎性体活性。通过流式细胞术检测FLICA（荧光标记的caspase-1抑制剂），在单核细胞和中性粒细胞中测量caspase-1活性，而通过Luminex和ELISA分别测量IL-1β和IL-18。通过定量PCR分析NLRP3，CASP1（procaspase-1）和IL1B（pro-IL-1β）的信使RNA（mRNA）表达，作为炎性体引发的量度。我们发现在菌血症急性期患者体内先天免疫细胞中诱导的caspase-1活性被诱导，随后IL-18释放，表明炎性体的激活。SAB患者之间的caspase-1活性存在很大的个体差异。我们还发现了炎症小体引发的改变，其中NLRP3的mRNA水平较低，并伴随着IL1B的mRNA水平升高。