关键词: IgG IgM antibodies bacteriophage future medicine humoral immunity immunogenicity neutralization phage therapy

Mesh : Animals Antibodies, Viral / blood Caudovirales / classification immunology Cytokines / blood Immunity, Humoral Immunization Immunoglobulin G / blood Immunoglobulin M / blood Male Mice Viral Proteins / immunology Virus Diseases / immunology

来  源:   DOI:10.3390/v13071241   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
Bacteriophages are promising antibacterial agents. Although they have been recognized as bacterial viruses and are considered to be non-interacting with eukaryotic cells, there is growing evidence that phages may have a significant impact on the immune system via interactions with macrophages, neutrophils, and T-cell polarization. In this study, the influence of phages of podovirus, siphovirus, and myovirus morphotypes on humoral immunity of CD-1 mice was investigated. In addition, tissue distribution of the phages was tested in these mice. No common patterns were found either in the distribution of phages in mice or in changes in the levels of cytokines in the sera of mice once injected with phages. Importantly, pre-existing IgM-class antibodies directed against capsid proteins of phages with myovirus and siphovirus morphotypes were identified in mice before immunization. After triple immunization of CD1-mice with phages without any adjuvant, levels of anti-phage serum polyclonal IgG antibodies increased. Immunogenic phage proteins recognized by IgM and/or IgG antibodies were identified using Western blot analysis and mass spectrometry. In addition, mice serum collected after immunization demonstrated neutralizing properties, leading to a substantial decrease in infectivity of investigated phages with myovirus and siphovirus morphotypes. Moreover, serum samples collected before administration of these phages exhibited some ability to reduce the phage infectivity. Furthermore, Proteus phage PM16 with podovirus morphotype did not elicit IgM or IgG antibodies in immunized mice, and no neutralizing activities against PM16 were revealed in mouse serum samples before and after immunization.
摘要:
噬菌体是有前途的抗菌剂。尽管它们已被认为是细菌病毒,并且被认为与真核细胞不相互作用,越来越多的证据表明,噬菌体可能通过与巨噬细胞的相互作用对免疫系统产生重大影响,中性粒细胞,和T细胞极化。在这项研究中,podovirus噬菌体的影响,siphovirus,研究了肌病毒形态对CD-1小鼠体液免疫的影响。此外,在这些小鼠中测试了噬菌体的组织分布。在小鼠噬菌体的分布或注射噬菌体后小鼠血清中细胞因子水平的变化中都没有发现共同的模式。重要的是,免疫前在小鼠中鉴定出预先存在的IgM类抗体,该抗体针对具有肌病毒和syphovirus形态型的噬菌体的衣壳蛋白.用无任何佐剂的噬菌体对CD1小鼠进行三重免疫后,抗噬菌体血清多克隆IgG抗体水平升高。使用蛋白质印迹分析和质谱鉴定由IgM和/或IgG抗体识别的免疫原性噬菌体蛋白。此外,免疫后收集的小鼠血清证明了中和特性,导致所研究的噬菌体的传染性大幅下降。此外,在施用这些噬菌体之前收集的血清样品显示出降低噬菌体感染性的一些能力。此外,具有podovirus形态型的变形杆菌噬菌体PM16在免疫小鼠中没有引起IgM或IgG抗体,免疫前后,小鼠血清样品中均未发现对PM16的中和活性。
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