Boontham Pisake, Robins Adrian, Chandran Palanichamy, Pritchard David, Cámara Miguel, Williams Paul, Chuthapisith Suebwong, McKechnie Alasdair, Rowlands Brian J, Eremin Oleg
Division of Surgery, University of Nottingham, Nottingham NG7 2UH, U.K.
Clin Sci (Lond). 2008 Dec;115(11):343-51. doi: 10.1042/CS20080018.
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.
致病细菌利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，我们检测了这些分子对正常人体外免疫功能的影响，并将其与脓毒症患者的免疫变化进行了比较，脓毒症患者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细胞的活化与增殖，并下调树突状细胞上共刺激分子的表达；在混合淋巴细胞树突状细胞反应中，白细胞介素-4和白细胞介素-10的分泌增加，但肿瘤坏死因子-α、干扰素-γ和白细胞介素-6减少。群体感应信号分子诱导树突状细胞和CD4(+)细胞凋亡，但不诱导CD8(+)细胞凋亡。脓毒症患者的树突状细胞减少，体外共刺激分子表达缺陷，对同种异体T淋巴细胞的刺激功能失调。脓毒症患者还表现出树突状细胞凋亡增强、CD4(+)辅助性T细胞1/辅助性T细胞2细胞凋亡率差异以及混合淋巴细胞树突状细胞反应中辅助性T细胞1/辅助性T细胞2细胞细胞因子谱改变。脓毒症患者的免疫变化模式反映了群体感应信号分子对正常人免疫细胞体外反应的影响，这表明群体感应信号分子应作为脓毒症免疫功能障碍的一个原因进行进一步研究。
