Apa2H1, the first head domain of Apa2 trimeric autotransporter adhesin, activates mouse bone marrow‐derived dendritic cells and immunization with Apa2H1 protects against Actinobacillus pleuropneumoniae infection
Apa2H1, the first head domain of Apa2 trimeric autotransporter adhesin, activates mouse bone marrow‐derived dendritic cells and immunization with Apa2H1 protects against Actinobacillus pleuropneumoniae infection
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DOI：
10.1016/j.molimm.2016.12.004
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发表时间：
2017
影响因子：
3.6
通讯作者：
Wanhai Qin;Lei Wang;Ruidong Zhai;Qiu-yue Ma;Jianfang Liu;Chun-tong Bao;Diangang Sun;Hu Zhang
中科院分区：
文献类型：
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作者：
Wanhai Qin;Lei Wang;Ruidong Zhai;Qiu-yue Ma;Jianfang Liu;Chun-tong Bao;Diangang Sun;Hu Zhang
胸膜肺炎放线杆菌是引起猪胸膜肺炎的病原菌，给世界养猪业造成巨大的经济损失。然而，由于各种血清型和缺乏针对该病原体的交叉保护，市场上没有有效的亚单位疫苗。因此，保护性成分的筛选对疫苗研制具有重要意义。我们以前的研究表明，三聚体的自转运蛋白粘附素是重要的毒力因子。胸膜肺炎为了确定Apa 2的功能性头部结构域（Apa 2 H1）在疫苗开发中的潜在作用，Apa 2是在A.在胸膜肺炎中，我们使用原核表达系统获得了天然样三聚体Apa 2 H1，并将Apa 2 H1与骨髓来源的树突状细胞（BMDC）体外共培养导致BMDC成熟，其特征在于CD 83、MHC-II、CCR 7、ICAM-1的上调以及与B淋巴细胞刺激相关的因子如增殖诱导配体（APRIL）的表达增加，B淋巴细胞刺激因子（BLyS）和B细胞活化因子（BAFF）。体内结果显示，Apa 2 H1疫苗接种导致抗原特异性抗体的稳健产生，适度诱导混合Th 1和Th 2免疫，损害细菌定殖和传播，并提高小鼠存活率。这项研究首次表明Apa 2 H1具有抗原性，可用作抗A亚单位疫苗的组分。为研制抗A.胸膜肺炎
Actinobacillus pleuropneumoniaeis the causative pathogen of porcine pleuropneumonia, which results in large economic losses in the pig industry worldwide. There are, however, no effective subunit vaccines are available in the market owing to the various serotypes and the absence of cross-protection against this pathogen. Therefore, the selection of protective components is of great significance for vaccine development. We previously showed that trimeric autotransporter adhesins are important virulence factors ofA. pleuropneumoniae. To determine the potential role in vaccine development of the functional head domain (Apa2H1) of Apa2, a trimeric autotransporter adhesin found inA. pleuropneumoniae, we obtained nature-like trimeric Apa2H1 using a prokaryotic expression system and co-culture of Apa2H1 with bone marrow derived dendritic cells (BMDCs) in vitro resulted in maturation of BMDCs, characterised by the up-regulation of CD83, MHC-II, CCR7, ICAM-I and the increased expression of factors related to B lymphoid cells stimulation, such as proliferation-inducing ligand (APRIL), B lymphocyte stimulator (BLyS) and B cell activating factor (BAFF). The in vivo results showed that vaccination with Apa2H1 resulted in the robust production of antigen-specific antibodies, modestly induced mixed Th1 and Th2 immunity, impaired bacterial colonization and dissemination, and improved mouse survival rates. This study is the first to show that Apa2H1 is antigenic and can be used as a component of a subunit vaccine againstA. pleuropneumoniaeinfection, providing valuable reference material for the development of an effective vaccine againstA. pleuropneumoniae.