In vitro and in vivo properties of the bovine antimicrobial peptide, Bactenecin 5
In vitro and in vivo properties of the bovine antimicrobial peptide, Bactenecin 5
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DOI：
10.1371/journal.pone.0210508
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发表时间：
2019-01-09
期刊：
影响因子：
3.7
通讯作者：
Willcocks, S. J.
中科院分区：
文献类型：
--
作者：
Price, R. L.;Bugeon, L.;Willcocks, S. J.
抗菌肽（AMP）是先天免疫系统的一部分，因其杀死病原微生物的能力而得到充分研究。然而，许多也具有重要的免疫调节作用，这一领域有潜力开发新的治疗方法，以补充传统的方法，如使用抗生素。在这里，我们验证了富含脯氨酸的牛AMP，Bactenecin 5（Bac 5）的杀微生物和免疫调节潜力。我们证明了广泛的抗菌活性，包括对一些分枝杆菌物种，这是鱼，牛和人类的重要病原体。Bac 5能够激活巨噬细胞样THP-1细胞，并且当与M. marinum。此外，Bac 5使A549上皮细胞对TNF-α的刺激敏感。我们首次在体内检测了Bac 5的活性，并在斑马鱼（Danio rerio）感染的胚胎模型中显示它是巨噬细胞的有效趋化因子。Bac 5还支持在M. marinum。在缺乏宿主适应性免疫的情况下，外源性注射Bac 5能够减缓，但不能预防，斑马鱼感染M。marinum。
Antimicrobial peptides (AMP), part of the innate immune system, are well studied for their ability to kill pathogenic microorganisms. However, many also possess important immunomodulatory effects, and this area has potential for the development of novel therapies to supplement traditional methods such as the use of antibiotics. Here, we characterise the microbicidal and immunomodulatory potential of the proline-rich bovine AMP, Bactenecin 5 (Bac5). We demonstrate broad antimicrobial activity, including against some mycobacterial species, which are important pathogens of fish, cattle and humans. Bac5 is able to activate macrophage-like THP-1 cells and can synergistically trigger the upregulation of tnf-alpha when co-stimulated with M. marinum. Furthermore, Bac5 sensitises A549 epithelial cells to stimulation with TNF-alpha. For the first time, we characterise the activity of Bac5 in vivo, and show it to be a potent chemokine for macrophages in the zebrafish (Danio rerio) embryo model of infection. Bac5 also supports the early recruitment of neutrophils in the presence of M. marinum. In the absence of host adaptive immunity, exogenous injected Bac5 is able to slow, although not prevent, infection of zebrafish with M. marinum.