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首页> 外文期刊>Infection and immunity >The Pseudomonas aeruginosaQuorum-Sensing Signal MoleculeN-(3-Oxododecanoyl)-l-Homoserine Lactone Has Immunomodulatory Activity
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The Pseudomonas aeruginosaQuorum-Sensing Signal MoleculeN-(3-Oxododecanoyl)-l-Homoserine Lactone Has Immunomodulatory Activity

机译：铜绿假单胞菌群体感应信号分子N-（3-氧十二烷酰基）-1-高丝氨酸内酯具有免疫调节活性

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Diverse gram-negative bacterial cells communicate with each other by using diffusible N-acyl homoserine lactone (AHL) signal molecules to coordinate gene expression with cell population density. Accumulation of AHLs above a threshold concentration renders the population “quorate,” and the appropriate target gene is activated. In pathogenic bacteria, such as Pseudomonas aeruginosa, AHL-mediated quorum sensing is involved in the regulation of multiple virulence determinants. We therefore sought to determine whether the immune system is capable of responding to these bacterial signal molecules. Consequently the immunomodulatory properties of the AHLsN-(3-oxododecanoyl)-l-homoserine lactone (OdDHL) and N-(3-oxohexanoyl)-l-homoserine lactone (OHHL) were evaluated in murine and human leukocyte immunoassays in vitro. OdDHL, but not OHHL, inhibited lymphocyte proliferation and tumor necrosis factor alpha production by lipopolysaccharide-stimulated macrophages. Furthermore, OdDHL simultaneously and potently down-regulated the production of IL-12, a Th-1-supportive cytokine. At high concentrations (>7 × 10?5 M) OdDHL inhibited antibody production by keyhole limpet hemocyanin-stimulated spleen cells, but at lower concentrations (<7 × 10?5 M), antibody production was stimulated, apparently by increasing the proportion of the immunoglobulin G1 (IgG1) isotype. OdDHL also promoted IgE production by interleukin-4-stimulated human peripheral blood mononuclear cells. These data indicate that OdDHL may influence the Th-1–Th-2 balance in the infected host and suggest that, in addition to regulating the expression of virulence determinants, OdDHL may contribute to the pathogenesis of P. aeruginosa infections by functioning as a virulence determinant per se.
机译：多种革兰氏阴性细菌细胞通过使用可扩散的 N -酰基高丝氨酸内酯（AHL）信号分子相互沟通，以协调基因表达与细胞群体密度。超过阈值浓度的AHL积累使种群“数量化”，并且适当的靶基因被激活。在诸如铜绿假单胞菌（Pseudomonas aeruginosa）的致病菌中，AHL介导的群体感应参与了多种毒力决定因素的调控。因此，我们试图确定免疫系统是否能够响应这些细菌信号分子。因此，AHLs N -（3-oxododecanoyl）-1-高丝氨酸内酯（OdDHL）和 N -（3-oxohexanoyl）-1-高丝氨酸内酯的免疫调节特性（ OHHL）在鼠和人白细胞免疫测定中进行了体外评估。 OdDHL，而不是OHHL，通过脂多糖刺激的巨噬细胞抑制淋巴细胞增殖和肿瘤坏死因子α的产生。此外，OdDHL同时有效地下调了Th-12支持性细胞因子IL-12的产生。在高浓度（> 7×10 ？5 M）下，OdDHL抑制钥孔血蓝蛋白刺激的脾细胞产生抗体，而在较低浓度（<7×10 ？5 ）下M），显然通过增加免疫球蛋白G1（IgG1）同种型的比例来刺激抗体产生。 OdDHL还通过白介素4刺激的人类外周血单核细胞促进IgE的产生。这些数据表明，OdDHL可能会影响被感染宿主中Th-1–Th-2的平衡，并表明，除了调节毒力决定因素的表达外，OdDHL可能还有助于 P的发病。通过作为毒力决定因素本身来感染铜绿假单胞菌。

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