Significant immunomodulatory effects of Pseudomonas aeruginosa quorum-sensing signal molecules: possible link in human sepsis
Significant immunomodulatory effects of Pseudomonas aeruginosa quorum-sensing signal molecules: possible link in human sepsis
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DOI：
10.1042/cs20080018
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发表时间：
2008-12-01
期刊：
影响因子：
6
通讯作者：
Eremin, Oleg
中科院分区：
文献类型：
--
作者：
Boontham, Pisake;Robins, Adrian;Eremin, Oleg
病原菌使用群体感应信号分子来协调毒力基因的表达。基于动物的研究已经证明了群体感应信号分子的免疫调节作用。在本研究中，我们在体外检测了这些分子对正常人体免疫功能的影响，并将其与脓毒症患者的免疫变化进行了比较，在脓毒症患者的血清中检测到了群体感应信号分子。群体感应信号分子抑制正常树突状细胞和T细胞的激活和增殖，下调树突状细胞表面共刺激分子的表达；在混合淋巴细胞树突状细胞反应中，IL-4和IL-10的分泌增加，而肿瘤坏死因子-α、干扰素-γ和IL-6的分泌减少。群体感应信号分子可诱导树突状细胞和CD4(+)细胞的凋亡，但不能诱导CD8(+)细胞的凋亡。脓毒症患者的树突状细胞被耗尽，体外表现出共刺激分子表达缺陷和同种异体T淋巴细胞刺激功能障碍。脓毒症患者外周血中树突状细胞的凋亡率增加，CD4(+)Th1/Th2(T辅助细胞1/2)细胞凋亡率升高，Th1/Th2细胞因子谱改变。脓毒症患者的免疫学变化模式反映了群体感应信号分子在体外对正常人免疫细胞反应的影响，提示群体感应信号分子作为脓毒症免疫功能障碍的原因值得进一步研究。
Pathogenic bacteria use quorum-sensing signal molecules to co-ordinate the expression of virulence genes. Animal-based studies have demonstrated the immunomodulatory effects of quorum-sensing signal molecules. In the present study, we have examined the impact of these molecules on normal human immune function in vitro and compared this with immune changes in patients with sepsis where quorum-sensing signal molecules were detected in the sera of patients. Quorum-sensing signal molecules inhibited normal dendritic cell and T-cell activation and proliferation, and down-regulated the expression of co-stimulatory molecules on dendritic cells; in MLDCRs (mixed lymphocyte dendritic cell reactions), secretion of IL (interleukin)-4 and IL-10 was enhanced, but TNF-alpha (tumour necrosis factor-alpha), IFN-gamma (interferon-gamma) and IL-6 was reduced. Quorum-sensing signal molecules induced apoptosis in dendritic cells and CD4(+) cells, but not CD8(+) cells. Dendritic cells from patients with sepsis were depleted and ex vivo showed defective expression of co-stimulatory molecules and dysfunctional stimulation of allogeneic T-lymphocytes. Enhanced apoptosis of dendritic cells and differential CD4(+) Th1/Th2 (T-helper 1/2) cell apoptotic rate, and modified Th1/Th2 cell Cytokine profiles in MLDCRs were also demonstrated in patients with sepsis. The pattern of immunological changes in patients with sepsis mirrors the effects of quorum-sensing signal molecules on responses of immune cells from normal individuals in vitro, suggesting that quorum-sensing signal molecules should be investigated further as a cause of immune dysfunction in sepsis.