The Antimicrobial Peptide, Bactenecin 5, Supports Cell-Mediated but Not Humoral Immunity in the Context of a Mycobacterial Antigen Vaccine Model.

The Antimicrobial Peptide, Bactenecin 5, Supports Cell-Mediated but Not Humoral Immunity in the Context of a Mycobacterial Antigen Vaccine Model.
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抗菌肽 Bactenecin 5 在分枝杆菌抗原疫苗模型中支持细胞介导的免疫,但不支持体液免疫。

DOI:
10.3390/antibiotics9120926
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发表时间:
2020-12-19
期刊:
Antibiotics (Basel, Switzerland)
影响因子:
--
通讯作者:
Willcocks SJ
Willcocks SJ
中科院分区:
其他
文献类型:
--
作者:
Munshi T;Sparrow A;Wren BW;Reljic R;Willcocks SJ

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Bactenecin (Bac) 5是一种牛抗菌肽(AMP),能够通过抑制蛋白质合成来杀死某些种类的细菌。Bac5和其他AMPs也被证明具有趋化特性,可以诱导先天免疫细胞表达炎症细胞因子。最近,人们开始研究amp作为新型疫苗佐剂的潜在用途。在目前的工作中,我们在体外使用小鼠巨噬细胞样细胞,在体外使用人类扁桃体组织和在体内使用小鼠疫苗模型来表征Bac5的功能。我们报道了该肽在分离和与分枝杆菌抗原和整个惰性枯草芽孢杆菌孢子抗原共同呈现的情况下的作用。我们发现,在没有其他激动剂的情况下,Bac5可以触发小鼠巨噬细胞释放一氧化氮,并上调CD86、MHC-I和MHC-II等表面标志物的表达。当与分枝杆菌Ag85和枯草芽孢杆菌孢子偶联时,Bac5也能促进IFNγ的分泌。我们提供的证据表明,枯草芽孢杆菌孢子,而不是Bac5肽,在促进ag85b疫苗接种小鼠抗原特异性免疫球蛋白的产生中起强佐剂作用。我们的研究结果表明Bac5是早期细胞介导的宿主免疫反应的重要调节因子。
Bactenecin (Bac) 5 is a bovine antimicrobial peptide (AMP) capable of killing some species of bacteria through the inhibition of protein synthesis. Bac5 and other AMPs have also been shown to have chemotactic properties and can induce inflammatory cytokine expression by innate immune cells. Recently, AMPs have begun to be investigated for their potential use as novel vaccine adjuvants. In the current work, we characterise the functionality of Bac5 in vitro using murine macrophage-like cells, ex vivo using human tonsil tissue and in vivo using a murine model of vaccination. We report the effects of the peptide in isolation and in the context of co-presentation with mycobacterial antigen and whole, inert Bacillus subtilis spore antigens. We find that Bac5 can trigger the release of nitric oxide from murine macrophages and upregulate surface marker expression including CD86, MHC-I and MHC-II, in the absence of additional agonists. When coupled with mycobacterial Ag85 and B. subtilis spores, Bac5 also enhanced IFNγ secretion. We provide evidence that B. subtilis spores, but not the Bac5 peptide, act as strong adjuvants in promoting antigen-specific immunoglobulin production in Ag85B-vaccinated mice. Our findings suggest that Bac5 is an important regulator of the early cell-mediated host immune response.
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