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首页> 外文期刊>Vaccine >Imrnunostimulatory and antigen delivery properties of liposomes made up of total polar lipids from non-pathogenic bacteria leads to efficient induction of both innate and adaptive immune responses
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Imrnunostimulatory and antigen delivery properties of liposomes made up of total polar lipids from non-pathogenic bacteria leads to efficient induction of both innate and adaptive immune responses

机译:由来自非致病性细菌的总极性脂质组成的脂质体的免疫刺激和抗原传递特性可有效诱导先天和适应性免疫应答

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Novel liposomes prepared from total polar lipids of non-pathogenic bacteria, viz. Leptospira biflexa serovar Potac (designated leptosomes) and Mycobacterium smegmatis (designated smegmosomes) were evaluated for their adjuvant effects with various antigen presenting cells (APCs), viz. murine macrophage cell line, J774A.1 and bone marrow derived dendritic cells (BMDCs). These liposomes induced strong membrane fusion as evident from resonance energy transfer (RET) assays and effectively transferred the fluorescent probe to the membrane of these APCs. Moreover, both vesicles caused significant activation of APCs as revealed by release of proinflammatory cytokines (IL-6, IL-12, TNF-alpha) and enhanced expression of co-stimulatory signals and maturation markers (CD80, CD86, MHCII), which was significantly higher for smegmosomes as compared to leptosomes. Additionally, activation of APCs by liposomes correlated with their ability to stimulate allospecific T cell proliferation and IFN-gamma release. In contrast, conventional PC/chol liposomes failed to fuse and induced only a very low level of APC activation. Interestingly, the stimulatory activity of these lipid vesicles was restricted to APCs as they did not cause any significant activation or mitogenic effect on lymphocytes (B and T cells) in vitro. Overall, the activation of APCs by both leptosomes and smegmosomes correlated with activation of strong humoral and cell mediated immune responses in C57/BL6 mice to entrapped ovalbumin (OVA) and was significantly higher than those induced by conventional liposomes and alum, which failed to activate cytotoxic T lymphocytes (CTLs). Taken together these results demonstrate the adjuvant potential of these novel lipid vesicles that may simultaneously induce both innate and adaptive immune responses due to their immune stimulatory and antigen delivery properties
机译:由非致病细菌的总极性脂质制备的新型脂质体。用各种抗原呈递细胞(APC)评估了双侧钩端螺旋体血清型Potac(指定为脂质体)和耻垢分枝杆菌(指定为耻垢体)的佐剂作用。小鼠巨噬细胞系J774A.1和骨髓来源的树突状细胞(BMDC)。从共振能量转移(RET)分析中可以明显看出,这些脂质体诱导了牢固的膜融合,并将荧光探针有效地转移到了这些APC的膜上。而且,两个囊泡均通过促炎细胞因子(IL-6,IL-12,TNF-α)的释放以及共刺激信号和成熟标志物(CD80,CD86,MHCII)的表达增强而显着激活了APCs。相比于脂质体,耻垢体明显更高。此外,脂质体对APC的激活与其刺激同种异体T细胞增殖和IFN-γ释放的能力有关。相比之下,常规的PC /胆甾醇脂质体无法融合,只能诱导非常低水平的APC活化。有趣的是,这些脂质囊泡的刺激活性仅限于APC,因为它们在体外不会对淋巴细胞(B和T细胞)产生任何明显的激活或促有丝分裂作用。总体而言,细小体和包涵体对APC的激活与C57 / BL6小鼠对包埋的卵白蛋白(OVA)的强体液和细胞介导的免疫反应的激活相关,并且显着高于常规脂质体和明矾诱导的激活,而后者未能激活细胞毒性T淋巴细胞(CTL)。综上所述,这些结果证明了这些新型脂质囊泡的佐剂潜力,由于其免疫刺激和抗原传递特性,可同时诱导先天性和适应性免疫应答

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