EA7426 "Pathophysiology of Injury-Induced Immunosuppression", PI3, Université Claude Bernard Lyon-1 Hospices Civils de Lyon - bioMérieux, Lyon, France.
Open Innovation and Partnerships (OIP), bioMérieux S.A, Lyon, France.
Sci Rep. 2020 Jun 18;10(1):9918. doi: 10.1038/s41598-020-66695-2.
Patients that suffer from sepsis exhibit an early hyper-inflammatory immune response which can lead to organ failure and death. In our study, we assessed the immune modulation in the human in vivo endotoxemia model and compared it to ex vivo LPS stimulation using 38 transcriptomic markers. Blood was collected before and after 4 hours of LPS challenge and tested with the Immune Profiling Panel (IPP) using the FilmArray system. The use of IPP showed that markers from the innate immunity dominated the response to LPS in vivo, mainly markers related to monocytes and neutrophils. Comparing the two models, in vivo and ex vivo, revealed that most of the markers were modulated in a similar pattern (68%). Some cytokine markers such as TNF, IFN-γ and IL-1β were under-expressed ex vivo compared to in vivo. T-cell markers were either unchanged or up-modulated ex vivo, compared to a down-modulation in vivo. Interestingly, markers related to neutrophils were expressed in opposite directions, which might be due to the presence of cell recruitment and feedback loops in vivo. The IPP tool was able to capture the early immune response in both the human in vivo endotoxemia model, a translational model mimicking the immune response observed in septic patients.
患有败血症的患者表现出早期的过度炎症免疫反应，这可能导致器官衰竭和死亡。在我们的研究中，我们评估了人类体内内毒素血症模型中的免疫调节，并使用 38 个转录组标志物将其与体外 LPS 刺激进行了比较。在 LPS 挑战前和 4 小时后采集血液，并使用 FilmArray 系统的免疫分析面板 (IPP) 进行测试。IPP 的使用表明，先天免疫标志物主导了 LPS 在体内的反应，主要与单核细胞和中性粒细胞有关。比较体内和体外两种模型发现，大多数标志物以相似的模式进行调节（68%）。与体内相比，体外一些细胞因子标志物如 TNF、IFN-γ 和 IL-1β 的表达水平较低。与体内下调相比，体外 T 细胞标志物要么不变，要么上调。有趣的是，与中性粒细胞相关的标志物表达方向相反，这可能是由于体内存在细胞募集和反馈环。IPP 工具能够捕捉到人类体内内毒素血症模型中的早期免疫反应，该模型模拟了败血症患者观察到的免疫反应。
