Autophagy Is a Defense Mechanism Inhibiting Invasion and Inflammation During High-Virulent Haemophilus parasuis Infection in PK-15 Cells

Autophagy Is a Defense Mechanism Inhibiting Invasion and Inflammation During High-Virulent Haemophilus parasuis Infection in PK-15 Cells
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DOI:
10.3389/fcimb.2019.00093
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发表时间:
2019-04
影响因子:
5.7
通讯作者:
Chao-xiong Yue;Jinquan Li;Hui Jin;Kexin Hua;Wei Zhou;Yueyi Wang;Gui-rong Cheng;Dan Liu;Lang Xu;Yushan Chen;Yan Zeng
Chao-xiong Yue;Jinquan Li;Hui Jin;Kexin Hua;Wei Zhou;Yueyi Wang;Gui-rong Cheng;Dan Liu;Lang Xu;Yushan Chen;Yan Zeng
中科院分区:
医学2区
文献类型:
--
作者:
Chao-xiong Yue;Jinquan Li;Hui Jin;Kexin Hua;Wei Zhou;Yueyi Wang;Gui-rong Cheng;Dan Liu;Lang Xu;Yushan Chen;Yan Zeng

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细菌感染激活自噬,自噬通过特定机制限制病原体如副猪嗜血杆菌。自噬与H.副猪。然而,机制尚未澄清。在此,我们使用共聚焦显微镜、免疫印迹和透射电子显微镜(TEM)监测自噬过程,发现H。副猪链球菌SH 0165(强毒株)感染增强了自噬通量,而HN 0001(非毒株)感染则没有增强。AMPK/mTOR自噬途径是自噬启动所必需的,并且ATG 5、Beclin-1、ATG 7和ATG 16 L1在H.副猪感染此外,H. parasuis SH 0165则转而对抗入侵细菌和抑制炎症。我们进一步证实了自噬通过抑制NF-κB、p38和JNK MAPK信号通路来阻断SH 0165感染诱导的细胞因子IL-8、CCL 4和CCL 5的产生。因此,我们的研究结果表明,自噬可能作为一种细胞防御机制,在响应H。为自噬保护宿主抵抗H.副猪感染
Bacterial infections activate autophagy and autophagy restricts pathogens such as Haemophilus parasuis through specific mechanisms. Autophagy is associated with the pathogenesis of H. parasuis. However, the mechanisms have not been clarified. Here, we monitored autophagy processes using confocal microscopy, western blot, and transmission electron microscopy (TEM) and found that H. parasuis SH0165 (high-virulent strain) but not HN0001 (non-virulent strain) infection enhanced autophagy flux. The AMPK/mTOR autophagy pathway was required for autophagy initiation and ATG5, Beclin-1, ATG7, and ATG16L1 emerged as important components in the generation of the autophagosome during H. parasuis infection. Moreover, autophagy induced by H. parasuis SH0165 turned to fight against invaded bacteria and inhibit inflammation. Then we further demonstrated that autophagy blocked the production of the cytokines IL-8, CCL4, and CCL5 induced by SH0165 infection through the inhibition of NF-κB, p38, and JNK MAPK signaling pathway. Therefore, our findings suggest that autophagy may act as a cellular defense mechanism in response to H. parasuis and provide a new way that autophagy protects the host against H. parasuis infection.