寄生褐飞虱的 HbpA 可通过激活 MAPK 和 NF-κB 信号通路诱导 3D4/21 细胞产生炎症反应,并在用作免疫原时保护小鼠免受寄生褐飞虱的感染。

IF 3.7 1区 农林科学 Q1 VETERINARY SCIENCES
Zhen Yang, Yiwen Zhang, Qin Zhao, Senyan Du, Xiaobo Huang, Rui Wu, Qigui Yan, Xinfeng Han, Yiping Wen, San-Jie Cao
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引用次数: 0

摘要

寄生璃色杆菌通常是猪上呼吸道的良性共生菌,但毒株可引起以肺炎、脑膜炎和纤维素性多发性硬化症为特征的全身感染。寄生虫感染后强烈的肺部炎症反应是造成猪肺损伤和死亡的主要原因。由于缺乏广泛的交叉保护,疫苗接种未能控制该疾病。越来越多的证据表明,血红素结合蛋白 A (HbpA) 是一种潜在的毒力决定因子,也是开发更广泛疫苗的候选抗原。然而,HbpA 是否有助于寄生虫的毒力或对寄生虫有任何潜在的免疫保护作用尚不得而知。在这里,我们发现 HbpA 可诱导猪肺泡巨噬细胞(PAM,3D4/31)转录和分泌促炎细胞因子(IL-6、TNF-α 和 MCP-1)。HbpA 蛋白可被 3D4/21 巨噬细胞上的 Toll 样受体 2 和 4 识别,从而激活 MAP 激酶和 NF-κB 信号级联,并转录和分泌促炎细胞因子。HbpA 有助于 C57BL/6 小鼠的毒力和细菌肺定植,并在粘附宿主细胞和逃避肺巨噬细胞的杀菌作用方面发挥作用。此外,用 HbpA 免疫的小鼠对寄生虫 SC1401 的挑战具有部分保护作用。这些结果表明,HbpA 在寄生虫疾病的发病机制中起着重要作用,并为开发亚单位或嵌合体抗寄生虫疫苗奠定了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
HbpA from Glaesserella parasuis induces an inflammatory response in 3D4/21 cells by activating the MAPK and NF-κB signalling pathways and protects mice against G. parasuis when used as an immunogen.

Glaesserella parasuis is usually a benign swine commensal in the upper respiratory tract, but virulent strains can cause systemic infection characterized by pneumonia, meningitis, and fibrinous polyserositis. The intensive pulmonary inflammatory response following G. parasuis infection is the main cause of lung injury and death in pigs. Vaccination has failed to control the disease due to the lack of extended cross-protection. Accumulating evidence indicates that the heme-binding protein A (HbpA) is a potential virulence determinant and a promising antigen candidate for the development of a broader range of vaccines. However, it is not yet known whether HbpA contributes to G. parasuis virulence or has any potential immune protective effects against G. parasuis. Here, we show that HbpA can induce the transcription and secretion of proinflammatory cytokines (IL-6, TNF-α, and MCP-1) in porcine alveolar macrophages (PAM, 3D4/31). The HbpA protein is recognized by Toll-like receptors 2 and 4 on 3D4/21 macrophages, resulting in the activation of MAP kinase and NF-κB signalling cascades and the transcription and secretion of proinflammatory cytokines. HbpA contributes to virulence and bacterial pulmonary colonization in C57BL/6 mice and plays a role in adhesion to host cells and evasion of the bactericidal effect of pulmonary macrophages. In addition, mice immunized with HbpA were partially protected against challenge by G. parasuis SC1401. The results suggest that HbpA plays an important role in the pathogenesis of disease caused by G. parasuis and lay a foundation for the development of a subunit or chimeric anti-G. parasuis vaccine.

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来源期刊
Veterinary Research
Veterinary Research 农林科学-兽医学
CiteScore
7.00
自引率
4.50%
发文量
92
审稿时长
3 months
期刊介绍: Veterinary Research is an open access journal that publishes high quality and novel research and review articles focusing on all aspects of infectious diseases and host-pathogen interaction in animals.
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