Some bacterial pathogens utilize cell-cell communication systems, such as quorum sensing (QS), to coordinate genetic programs during host colonization and infection. The human-restricted pathosymbiont Streptococcus pyogenes (Group A Streptococcus, GAS) uses the Rgg2/Rgg3 QS system to modify the bacterial surface, enabling biofilm formation and lysozyme resistance. Here, we demonstrate that innate immune cell responses to GAS are substantially altered by the QS status of the bacteria. We found that macrophage activation, stimulated by multiple agonists and assessed by cytokine production and NFkB activity, was substantially suppressed upon interaction with QS-active GAS but not QS-inactive bacteria. Neither macrophage viability nor bacterial adherence were seen as different between QS activity states, yet TNFa, IL-6, and IFNb levels and NFkB reporter activity were drastically lower following infection with QS-active GAS. Suppression required contact between viable bacteria and macrophages. A QS-regulated biosynthetic gene cluster (BGC) in the GAS genome, encoding several putative enzymes, was also required for macrophage modulation. Our findings suggest a model wherein upon contact with macrophages, QS-active GAS produce a BGC-derived factor capable of suppressing inflammatory responses. The suppressive capability of QS-active GAS is abolished after treatment with a specific QS inhibitor. These observations suggest that interfering with the ability of bacteria to collaborate via QS can serve as a strategy to counteract microbial efforts to manipulate host defenses.

中文翻译：

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链球菌群体感应系统可抑制先天免疫

一些细菌病原体利用细胞间通信系统（例如群体感应（QS））在宿主定植和感染过程中协调遗传程序。人类限制性病原菌化脓性链球菌（A组链球菌，GAS）使用Rgg2 / Rgg3 QS系统修饰细菌表面，从而实现生物膜形成和溶菌酶抗性。在这里，我们证明对细菌GAS的先天性免疫细胞反应实质上被细菌的QS状态所改变。我们发现，与QS活性GAS而非QS惰性细菌相互作用后，被多种激动剂刺激并通过细胞因子产生和NFkB活性评估的巨噬细胞活化被显着抑制。在QS活性状态之间，巨噬细胞生存力和细菌粘附均未见差异，但感染QS活性GAS后，TNFa，IL-6和IFNb水平以及NFkB报告基因活性均大大降低。抑制需要活细菌和巨噬细胞之间的接触。GAS基因组中受QS调控的生物合成基因簇（BGC），巨噬细胞调节还需要编码几种推定的酶。我们的发现提出了一种模型，其中与巨噬细胞接触后，QS活性GAS产生能够抑制炎症反应的BGC衍生因子。用特定的QS抑制剂处理后，对QS活性GAS的抑制能力将消失。这些观察结果表明，干扰细菌通过QS进行协作的能力可以作为抵抗微生物操纵宿主防御力的策略。