Adh enhances Actinobacillus pleuropneumoniae pathogenicity by binding to OR5M11 and activating p38 which induces apoptosis of PAMs and IL-8 release.
Adh enhances Actinobacillus pleuropneumoniae pathogenicity by binding to OR5M11 and activating p38 which induces apoptosis of PAMs and IL-8 release.
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Adh 通过与 OR5M11 结合并激活 p38 来增强胸膜肺炎放线杆菌的致病性，从而诱导 PAM 凋亡和 IL-8 释放
DOI：
10.1038/srep24058
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发表时间：
2016-04-05
影响因子：
4.6
通讯作者：
Lei L
中科院分区：
文献类型：
--
作者：
Wang L;Qin W;Zhang J;Bao C;Zhang H;Che Y;Sun C;Gu J;Feng X;Du C;Han W;Richard PL;Lei L
三聚体自转运蛋白粘附素（TAA）家族成员在革兰氏阴性病原体与宿主细胞的粘附中起着至关重要的作用，但TAA的免疫发病机制尚不清楚。本实验室前期研究表明，猪胸膜肺炎放线杆菌（Actinobacilluspleuropneumoniae，A。胸膜肺炎）是完全细菌致病性所必需的。肺泡巨噬细胞是抵抗呼吸道感染的第一道防线。本研究比较了猪肺泡巨噬细胞（PAM）和野生型A。通过基因微阵列、免疫沉淀等技术，对猪胸膜肺炎（5 b WT）或Adh缺失株（5 b ΔAdh）进行基因分型。我们发现Adh与PAMs膜蛋白OR 5 M11（一种嗅觉受体）相互作用，通过激活p38 MAPK信号通路导致IL-8的高水平分泌。随后，观察到通过Fax和Bax信号通路激活的PAMS细胞凋亡，然后激活半胱氨酸蛋白酶8、9和3。在小鼠和仔猪体内感染模型中也证实了Adh的免疫致病作用。这些结果为TAAs增强A.胸膜肺炎总之，这些数据揭示了Adh蛋白作为毒力因子的高度通用性，并为TAAs的免疫致病作用提供了新的见解。
Members of the Trimeric Autotransporter Adhesin (TAA) family play a crucial role in the adhesion of Gram-negative pathogens to host cells, but the immunopathogenesis of TAAs remains unknown. Our previous studies demonstrated that Adh from Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is required for full bacterial pathogenicity. Alveolar macrophages are the first line of defense against respiratory infections. This study compared the interactions between porcine alveolar macrophages (PAMs) and wild-type A. pleuropneumoniae (5b WT) or an Adh-deletion strain (5b ΔAdh) via gene microarray, immunoprecipitation and other technologies. We found that Adh was shown to interact with the PAMs membrane protein OR5M11, an olfactory receptor, resulting in the high-level secretion of IL-8 by activation of p38 MAPK signaling pathway. Subsequently, PAMs apoptosis via the activation of the Fax and Bax signaling pathways was observed, followed by activation of caspases 8, 9, and 3. The immunological pathogenic roles of Adh were also confirmed in both murine and piglets infectious models in vivo. These results identify a novel immunological strategy for TAAs to boost the pathogenicity of A. pleuropneumoniae. Together, these datas reveal the high versatility of the Adh protein as a virulence factor and provide novel insight into the immunological pathogenic role of TAAs.