Occludin and collagen IV degradation mediated by the T9SS effector SspA contributes to blood-brain barrier damage in ducks during Riemerella anatipestifer infection

文献类型： 外文期刊

第一作者： Chen, Zongchao

作者： Chen, Zongchao;Yu, Yang;Yu, Shengqing;Chen, Zongchao;Zhu, Min;Liu, Dan;Wu, Mengsi;Niu, Pengfei;Ding, Chan;Yu, Shengqing;Yu, Shengqing

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关键词： Riemerella anatipestifer; blood-brain barrier; T9SS; SspA; occludin; collagen IV

期刊名称：VETERINARY RESEARCH （ 影响因子：4.4； 五年影响因子：4.3 ）

ISSN： 0928-4249

年卷期： 2024 年 55 卷 1 期

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收录情况： SCI

摘要： Riemerella anatipestifer infection is characterized by meningitis with neurological symptoms in ducklings and has adversely affected the poultry industry. R. anatipestifer strains can invade the duck brain to cause meningitis and neurological symptoms, but the underlying mechanism remains unknown. In this study, we showed that obvious clinical symptoms, an increase in blood-brain barrier (BBB) permeability, and the accumulation of inflammatory cytokines occurred after intravenous infection with the Yb2 strain but not the mutant strain Yb2 Delta sspA, indicating that Yb2 infection can lead to cerebrovascular dysfunction and that the type IX secretion system (T9SS) effector SspA plays a critical role in this pathological process. In addition, we showed that Yb2 infection led to rapid degradation of occludin (a tight junction protein) and collagen IV (a basement membrane protein), which contributed to endothelial barrier disruption. The interaction between SspA and occludin was confirmed by coimmunoprecipitation. Furthermore, we found that SspA was the main enzyme mediating occludin and collagen IV degradation. These data indicate that R. anatipestifer SspA mediates occludin and collagen IV degradation, which functions in BBB disruption in R. anatipestifer-infected ducks. These findings establish the molecular mechanisms by which R. anatipestifer targets duckling endothelial cell junctions and provide new perspectives for the treatment and prevention of R. anatipestifer infection.

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