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Effects of Staphylococcus aureus Bacteriophage K on Expression of Cytokines and Activation Markers by Human Dendritic Cells In Vitro

机译:金黄色葡萄球菌噬菌体K对人树突状细胞体外细胞因子表达和激活标记的影响

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摘要

A potential concern with bacteriophage (phage) therapeutics is a host-versus-phage response in which the immune system may neutralize or destroy phage particles and thus impair therapeutic efficacy, or a strong inflammatory response to repeated phage exposure might endanger the patient. Current literature is discrepant with regard to the nature and magnitude of innate and adaptive immune response to phages. The purpose of this work was to study the potential effects of Staphylococcus aureus phage K on the activation of human monocyte-derived dendritic cells. Since phage K acquired from ATCC was isolated around 90 years ago, we first tested its activity against a panel of 36 diverse S. aureus clinical isolates from military patients and found that it was lytic against 30/36 (83%) of strains. Human monocyte-derived dendritic cells were used to test for an in vitro phage-specific inflammatory response. Repeated experiments demonstrated that phage K had little impact on the expression of pro- and anti-inflammatory cytokines, or on MHC-I/II and CD80/CD86 protein expression. Given that dendritic cells are potent antigen-presenting cells and messengers between the innate and the adaptive immune systems, our results suggest that phage K does not independently affect cellular immunity or has a very limited impact on it.
机译:噬菌体(噬菌体)疗法的潜在问题是宿主对噬菌体的反应,其中免疫系统可能中和或破坏噬菌体颗粒,从而削弱治疗功效,或者对反复噬菌体暴露的强烈炎症反应可能危及患者。当前文献关于对噬菌体的先天性和适应性免疫反应的性质和大小尚不相同。这项工作的目的是研究金黄色葡萄球菌噬菌体K对人类单核细胞衍生树突状细胞活化的潜在影响。由于从ATCC获得的噬菌体K大约是90年前分离出来的,因此我们首先测试了它对一组来自军人的36种不同金黄色葡萄球菌临床分离株的活性,发现其可溶解30/36(83%)的菌株。人类单核细胞衍生的树突状细胞用于测试体外噬菌体特异性炎症反应。重复的实验表明,噬菌体K对促炎和消炎细胞因子的表达,或对MHC-I / II和CD80 / CD86蛋白表达的影响很小。鉴于树突状细胞是先天免疫系统和适应性免疫系统之间有效的抗原呈递细胞和信使,我们的结果表明噬菌体K不会独立影响细胞免疫或对其具有非常有限的影响。

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