Human β-defensin 2 plays a regulatory role in innate antiviral immunity and is capable of potentiating the induction of antigen-specific immunity.

Human β-defensin 2 plays a regulatory role in innate antiviral immunity and is capable of potentiating the induction of antigen-specific immunity.
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DOI:
10.1186/s12985-018-1035-2
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发表时间:
2018-08-08
期刊:
影响因子:
4.8
通讯作者:
Jang YS
Jang YS
中科院分区:
医学3区
文献类型:
--
作者:
Kim J;Yang YL;Jang SH;Jang YS

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抗微生物肽(AMP)主要以其对入侵微生物(包括病毒)的先天免疫防御而闻名。此外,最近的研究表明它们在免疫诱导中具有调节活性。鉴于大多数亚单位疫苗需要佐剂通过激活先天免疫来实现有效的免疫诱导,AMP是不仅刺激先天免疫应答而且刺激适应性免疫应答的合理候选分子。本研究以中东呼吸综合征冠状病毒(MERS-CoV)刺突蛋白(S RBD)的受体结合域(RBD)为模型抗原,研究了人β-防御素(HBD)2在体内外促进抗病毒免疫的能力。当使用HBD 2缀合的S RBD处理THP-1人单核细胞时,与仅用S RBD处理后表达的那些相比,抗病毒分子(IFN-β、IFN-γ、MxA、PKR和RNaseL)和初级免疫诱导分子(NOD 2、TNF-α、IL-1β和IL-6)的表达水平增强。能够募集白细胞(包括单核细胞/巨噬细胞、自然杀伤细胞、粒细胞、T细胞和树突细胞)的趋化因子的表达在HBD 2缀合的S RBD处理后也增加。更重要的是,用HBD 2缀合的S RBD免疫小鼠增强了S RBD的免疫原性,并引起比单独S RBD更高的S RBD特异性中和抗体应答。我们的结论是,HBD 2激活的主要抗病毒先天免疫反应,也可能介导诱导一个有效的适应性免疫反应,对结合的Ag。
Antimicrobial peptides (AMPs) are primarily known for their innate immune defense against invading microorganisms, including viruses. In addition, recent research has suggested their modulatory activity in immune induction. Given that most subunit vaccines require an adjuvant to achieve effective immune induction through the activation of innate immunity, AMPs are plausible candidate molecules for stimulating not only innate immune but also adaptive immune responses. In this study, we investigated the ability of human β-defensin (HBD) 2 to promote antiviral immunity in vitro and in vivo using a receptor-binding domain (RBD) of Middle East respiratory syndrome-coronavirus (MERS-CoV) spike protein (S RBD) as a model antigen (Ag). When HBD 2-conjugated S RBD was used to treat THP-1 human monocytic cells, the expression levels of antiviral (IFN-β, IFN-γ, MxA, PKR, and RNaseL) and primary immune-inducing (NOD2, TNF-α, IL-1β, and IL-6) molecules were enhanced compared to those expressed after treatment with S RBD only. The expression of chemokines capable of recruiting leukocytes, including monocytes/macrophages, natural killer cells, granulocytes, T cells, and dendritic cells, was also increased following HBD 2-conjugated S RBD treatment. More important, immunization of mice with HBD 2-conjugated S RBD enhanced the immunogenicity of the S RBD and elicited a higher S RBD-specific neutralizing antibody response than S RBD alone. We conclude that HBD 2 activates the primary antiviral innate immune response and may also mediate the induction of an effective adaptive immune response against a conjugated Ag.
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DOI: 10.1074/jbc.m206473200
发表时间: 2002-11-01
影响因子: 4.8
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