Laboratory Bacteriology Research, Department of Clinical Chemistry, Microbiology and Immunology, University Ghent, Medical Research Building II, De Pintelaan 185, 9000, Ghent, Belgium.
Center for Vaccinology, Ghent University Hospital, Ghent, Belgium.
Sci Rep. 2017 Aug 14;7(1):8004. doi: 10.1038/s41598-017-08336-9.
The ability of bacteriophages to kill bacteria is well known, as is their potential use as alternatives to antibiotics. As such, bacteriophages reach high doses locally through infection of their bacterial host in the human body. In this study we assessed the gene expression profile of peripheral blood monocytes from six donors for twelve immunity-related genes (i.e. CD14, CXCL1, CXCL5, IL1A, IL1B, IL1RN, IL6, IL10, LYZ, SOCS3, TGFBI and TNFA) induced by Staphylococcus aureus phage ISP and four Pseudomonas aeruginosa phages (i.e. PNM, LUZ19, 14-1 and GE-vB_Pae-Kakheti25). The phages were able to induce clear and reproducible immune responses. Moreover, the overall immune response was very comparable for all five phages: down-regulation of LYZ and TGFBI, and up-regulation of CXCL1, CXCL5, IL1A, IL1B, IL1RN, IL6, SOCS3 and TNFA. The observed immune response was shown to be endotoxin-independent and predominantly anti-inflammatory. Addition of endotoxins to the highly purified phages did not cause an immune response comparable to the one induced by the (endotoxin containing) phage lysate. In addition, the use of an intermediate level of endotoxins tipped the immune response to a more anti-inflammatory response, i.e. up-regulation of IL1RN and a strongly reduced expression of CXCL1 and CXCL5.
噬菌体杀死细菌的能力是众所周知的，它们也有可能作为抗生素的替代品。因此，噬菌体通过在人体感染其细菌宿主而在局部达到高剂量。在这项研究中，我们评估了来自六个供体的外周血单核细胞的基因表达谱，这些供体的十二个免疫相关基因（即 CD14、CXCL1、CXCL5、IL1A、IL1B、IL1RN、IL6、IL10、LYZ、SOCS3、TGFBI 和 TNFA）被金黄色葡萄球菌噬菌体 ISP 和四个铜绿假单胞菌噬菌体（即 PNM、LUZ19、14-1 和 GE-vB_Pae-Kakheti25）诱导。噬菌体能够诱导明确和可重复的免疫反应。此外，所有五种噬菌体的总体免疫反应非常相似：LYZ 和 TGFBI 的下调，以及 CXCL1、CXCL5、IL1A、IL1B、IL1RN、IL6、SOCS3 和 TNFA 的上调。观察到的免疫反应是内毒素非依赖性的，主要是抗炎性的。将内毒素添加到高度纯化的噬菌体中不会引起与噬菌体裂解物诱导的免疫反应相当的反应。此外，使用中等水平的内毒素会使免疫反应向更抗炎性反应倾斜，即 IL1RN 的上调和 CXCL1 和 CXCL5 的表达强烈降低。
