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首页> 外文期刊>Infection and immunity >The Toll-Like Receptor 4 Agonist Monophosphoryl Lipid A Augments Innate Host Resistance to Systemic Bacterial Infection
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The Toll-Like Receptor 4 Agonist Monophosphoryl Lipid A Augments Innate Host Resistance to Systemic Bacterial Infection

机译：类似Toll的受体4激动剂单磷酰脂质A增强了先天宿主对系统细菌感染的抵抗力。

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Monophosphoryl lipid A (MPLA) is a Toll-like receptor 4 (TLR4) agonist that is currently used as a vaccine adjuvant in humans. In this study, we evaluated the effect of MPLA treatment on the innate immune response to systemic bacterial infections in mice. Mice treated with MPLA after burn injury showed improved survival and less local and systemic dissemination of bacteria in a model of Pseudomonas aeruginosa burn wound infection. Prophylactic treatment with MPLA significantly enhanced bacterial clearance at the site of infection and reduced systemic dissemination of bacteria despite causing attenuation of proinflammatory cytokine production during acute intra-abdominal infection caused by cecal ligation and puncture. Administration of MPLA at 1 h after CLP also improved bacterial clearance but did not alter cytokine production. MPLA treatment increased the numbers of granulocytes, double-positive myeloid cells, and macrophages at sites of infection and increased the percentage and total numbers of myeloid cells mediating phagocytosis of bacteria. Depletion of Ly6G+ neutrophils, but not macrophages, eliminated the ability of MPLA treatment to improve bacterial clearance. The immunomodulatory effects of MPLA were absent in TLR4-deficient mice. In conclusion, these studies show that MPLA treatment significantly augments the innate immune response to bacterial infection by enhancing bacterial clearance despite the attenuation of proinflammatory cytokine production. The enhanced bacterial clearance is mediated, in part, by increased numbers of myeloid cells with effective phagocytic functions at sites of infection and is TLR4 dependent.
机译：单磷酰脂质A（MPLA）是Toll样受体4（TLR4）激动剂，目前被用作人类的疫苗佐剂。在这项研究中，我们评估了MPLA处理对小鼠对系统性细菌感染的先天免疫应答的影响。在铜绿假单胞菌烧伤创面感染模型中，烧伤后用MPLA处理的小鼠表现出更好的存活率，细菌的局部和全身散布减少。用MPLA进行预防性治疗可显着提高感染部位的细菌清除率，并减少细菌的全身传播，尽管会导致盲肠结扎和穿刺引起的急性腹腔感染期间促炎性细胞因子产生减弱。 CLP后1 h给予MPLA也可改善细菌清除率，但不会改变细胞因子的产生。 MPLA处理增加了感染部位的粒细胞，双重阳性髓样细胞和巨噬细胞的数量，并增加了介导细菌吞噬作用的髓样细胞的百分比和总数。 Ly6G + 中性粒细胞的耗竭，而不是巨噬细胞的耗竭，消除了MPLA处理提高细菌清除率的能力。在TLR4缺陷型小鼠中没有MPLA的免疫调节作用。总之，这些研究表明，MPLA治疗可通过增强细菌清除率来显着增强对细菌感染的先天免疫反应，尽管会降低促炎细胞因子的产生。增加的细菌清除率部分是由感染部位具有有效吞噬功能的髓样细胞数量增加所介导的，并且是TLR4依赖性的。

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