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首页> 外文期刊>Infection and immunity >A Bacterial Flagellin, Vibrio vulnificus FlaB, Has a Strong Mucosal Adjuvant Activity To Induce Protective Immunity
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A Bacterial Flagellin, Vibrio vulnificus FlaB, Has a Strong Mucosal Adjuvant Activity To Induce Protective Immunity

机译：细菌鞭毛蛋白，弧菌弧菌FlB，具有很强的粘膜佐剂活性，可诱导保护性免疫

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Flagellin, the structural component of flagellar filament in various locomotive bacteria, is the ligand for Toll-like receptor 5 (TLR5) of host cells. TLR stimulation by various pathogen-associated molecular patterns leads to activation of innate and subsequent adaptive immune responses. Therefore, TLR ligands are considered attractive adjuvant candidates in vaccine development. In this study, we show the highly potent mucosal adjuvant activity of a Vibrio vulnificus major flagellin (FlaB). Using an intranasal immunization mouse model, we observed that coadministration of the flagellin with tetanus toxoid (TT) induced significantly enhanced TT-specific immunoglobulin A (IgA) responses in both mucosal and systemic compartments and IgG responses in the systemic compartment. The mice immunized with TT plus FlaB were completely protected from systemic challenge with a 200× minimum lethal dose of tetanus toxin. Radiolabeled FlaB administered into the nasal cavity readily reached the cervical lymph nodes and systemic circulation. FlaB bound directly to human TLR5 expressed on cultured epithelial cells and consequently induced NF-κB and interleukin-8 activation. Intranasally administered FlaB colocalized with CD11c as patches in putative dendritic cells and caused an increase in the number of TLR5-expressing cells in cervical lymph nodes. These results indicate that flagellin would serve as an efficacious mucosal adjuvant inducing protective immune responses through TLR5 activation.
机译：鞭毛蛋白是各种机车细菌中鞭毛丝的结构成分，是宿主细胞Toll样受体5（TLR5）的配体。各种病原体相关分子模式对TLR的刺激会导致先天和随后的适应性免疫反应的激活。因此，TLR配体被认为是疫苗开发中有吸引力的佐剂候选物。在这项研究中，我们显示了创伤弧菌主要鞭毛蛋白（FlaB）的高效粘膜佐剂活性。使用鼻内免疫小鼠模型，我们观察到鞭毛蛋白与破伤风类毒素（TT）的共同给药在粘膜和全身腔室中均显着增强了TT特异性免疫球蛋白A（IgA）应答，而在全身腔室中则产生了IgG应答。用200倍最小致死剂量的破伤风毒素完全保护了TT + FlaB免疫的小鼠免受系统性攻击。放射性标记的FlaB进入鼻腔后很容易到达颈部淋巴结和全身循环。 FlaB直接与在培养的上皮细胞上表达的人TLR5结合，从而诱导NF-κB和白介素8激活。鼻内施用的FlaB与CD11c共同定位在假定的树突状细胞中，导致宫颈淋巴结中表达TLR5的细胞数量增加。这些结果表明，鞭毛蛋白将作为有效的粘膜佐剂，通过TLR5激活诱导保护性免疫应答。

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