BALB/c小鼠模型评估O4:KUT血清型副溶血弧菌的致病性及宿主免疫应答研究

Evaluation of the pathogenicity and host immune response of Vibrio parahaemolyticus Serotype (O4:KUT) using a BALB/c mouse model

  • 摘要:
    目的  本研究旨在评估O4:KUT血清型副溶血弧菌对BALB/c小鼠的致病能力及其在急性感染期引起的病理损伤和宿主免疫应答。
    方法  通过PCR技术对菌株(编号ICDC-VP01716)的毒力基因进行鉴定。 将1.0×109 菌落形成单位的菌株通过灌胃途径感染BALB/c小鼠,感染4h后处死小鼠,观察其结肠的病理变化,并对其结肠组织进行转录组学分析,以研究宿主的免疫反应。
    结果  ICDC-VP01716菌株携带tdhtlh两种毒力基因,以及T3SS1和T3SS2的部分效应子基因,同时含有黏附因子mam7vpadF等与黏附相关的毒力基因。 在高剂量感染4 h后,BALB/c小鼠表现出结肠轻度肿胀和肠腔积液等病理变化。 转录组学结果提示,宿主在感染后4 h内迅速激活了免疫相关通路和信号分子和相互作用的两个类别的通路, 以响应病原体的感染。
    结论  患者来源的O4:KUT菌株ICDC-VP01716具有与其他临床分离株相似的毒力基因谱,大剂量感染该菌株可使小鼠出现与人类腹泻相似的临床表现,进一步证实了其作为临床分离株的致病能力

     

    Abstract:
    Objective This study aims to investigate the pathogenicity of Vibrio parahaemolyticus serotype O4: KUT in BALB/c mice, with specific focus on the induced pathological damage and host immune responses during acute infection.
    Methods The virulence genes of the strain (ICDC-VP01716) were identified using PCR. Subsequently, BALB/c mice were infected with 1.0×109 colony forming unit of the strain via oral gavage. After 4 hours of infection, the mice were euthanized to observe pathological changes in the colon, and transcriptional analysis was performed on the colonic tissue to study the host's immune response.
    Results  The ICDC-VP01716 carries two toxin genes, tdh and tlh, as well as some effector genes of T3SS1 and T3SS2, and adhesion-related virulence genes such as mam7 and vpadF. After high-dose infection for 4 hours, BALB/c mice exhibited mild colonic swelling and intestinal fluid accumulation. Transcriptional analysis indicated that the host rapidly activated immune-related pathways and signaling molecules, as well as pathways involved in cellular interactions, within 4 hours of infection.
    Conclusion  The ICDC-VP01716 possesses a virulence gene profile similar to other clinical isolates. High-dose infection with this strain induces clinical manifestations in mice that resemble human diarrhea, further confirming its pathogenic potential as a clinical isolate.

     

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