Joint Research Unit Hospices Civils de Lyon-bioMérieux, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite, 69495 Lyon, France.
4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, 124 62 Athens, Greece.
Clin Immunol. 2021 May;226:108714. doi: 10.1016/j.clim.2021.108714. Epub 2021 Mar 16.
Lipopolysaccharide (LPS) and monophosphoryl lipid A (MPLA) induce, overall, similar transcriptional profiles in healthy individuals, although LPS has been shown to more potently induce pro-inflammatory cytokines. We explore herein whether MPLA could be considered as a synthetic replacement of LPS in immune functional assays to study anergy of immune cells in septic patients. Ex vivo whole blood stimulation with MPLA revealed a lower induction of the TNFα secreted protein in 20 septic patients (SP) compared to 10 healthy volunteers (HV), in agreement with monocyte anergy. Principal component analysis of the 93-gene molecular response to MPLA and LPS stimulation found that the main variability was driven by stimulation in HV and by pathophysiology in SP. MPLA was a stronger inducer of the HLA family genes than LPS in both populations, arguing for divergent signalling pathways downstream of TLR-4. In addition, MPLA appeared to present a more informative stratification potential within the septic population.
脂多糖 (LPS) 和单磷酰脂质 A (MPLA) 在健康个体中总体上诱导相似的转录谱，尽管 LPS 已被证明更能诱导促炎细胞因子。我们在此探讨 MPLA 是否可以被视为 LPS 在免疫功能测定中的合成替代物，以研究脓毒症患者免疫细胞的无能。与单核细胞无能一致，用 MPLA 对 20 名脓毒症患者 (SP) 的体外全血刺激显示 TNFα 分泌蛋白的诱导较低，而对 10 名健康志愿者 (HV) 的诱导较高。对 MPLA 和 LPS 刺激的 93 个基因分子反应的主成分分析发现，主要的可变性是由 HV 的刺激和 SP 的病理生理学驱动的。MPLA 在两种人群中均比 LPS 更强地诱导 HLA 家族基因，这表明 TLR-4 下游的信号通路存在差异。此外，MPLA 似乎在脓毒症人群中具有更强的分层潜力。
