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首页> 外文期刊>Infection and immunity >Cytolethal Distending Toxin Is Essential for Helicobacter hepaticus Colonization in Outbred Swiss Webster Mice
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Cytolethal Distending Toxin Is Essential for Helicobacter hepaticus Colonization in Outbred Swiss Webster Mice

机译：Cytolethal扩散毒素对于近交瑞士韦伯斯特小鼠的肝杆菌定殖是必不可少的

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Helicobacter hepaticus, which induces chronic hepatitis and typhlocolitis in susceptible mouse strains, produces a cytolethal distending toxin (CDT) consisting of CdtA, CdtB, and CdtC. A cdtB-deficient H. hepaticus isogenic mutant (HhcdtBm7) was generated and characterized for colonization parameters in four intestinal regions (jejunum, ileum, cecum, and colon) of outbred Swiss Webster (SW) mice. Inactivation of the cdtB gene abolished the ability of HhcdtBm7 to colonize female mice at both 8 and 16 weeks postinfection (wpi), whereas HhcdtBm7 colonized all of four intestinal regions of three of five males at 8 wpi and then was eliminated by 16 wpi. Wild-type (WT) H. hepaticus was detected in the corresponding intestinal regions of both male and female mice at 8 and 16 wpi; however, colonization levels of WT H. hepaticus in the cecum and colon of male mice were approximately 1,000-fold higher than in females (P < 0.0079) at 16 wpi. Infection with WT H. hepaticus, but not HhcdtBm7, at 8 wpi was associated with significantly increased mRNA level of ileal and cecal gamma interferon (IFN-γ) in females (P < 0.016 and 0.031 between WT H. hepaticus-infected and sham-dosed females, respectively). In contrast, the mRNA levels of IFN-γ were significantly higher in the colon (P < 0.0079) and trended to be higher in the cecum (P < 0.15) in the HhcdtBm7-colonized male mice versus the sham-dosed controls at 8 wpi. In addition, mRNA levels of ileal IFN-γ were significantly higher in the control females than males at 8 wpi (P < 0.016). There were significantly higher Th1-associated immunoglobulin G2a (IgG2a), Th2-associated IgG1 and mucosal IgA (P < 0.002, 0.002, 0.002, respectively) responses in the mice infected with WT H. hepaticus when compared to HhcdtBm7 at 16 wpi. Colonic interleukin-10 (IL-10) expressions at 16 wpi were significantly lower in both female and male mice colonized by WT H. hepaticus or in males transiently colonized through 8 wpi by HhcdtBm7 versus control mice (P < 0.0159). These lines of evidence indicate that (i) H. hepaticus CDT plays a crucial role in the persistent colonization of H. hepaticus in SW mice; (ii) SW female mice are more resistant to H. hepaticus colonization than male mice; (iii) there was persistent colonization of WT H. hepaticus in cecum, colon, and jejunum but only transient colonization of H. hepaticus in the ileum of female mice; (iv) H. hepaticus colonization was associated with down-regulation of colonic IL-10 production.
机译： Helicobacter hepaticus 会在易感小鼠品系中诱发慢性肝炎和鼠疫，产生由CdtA，CdtB和CdtC组成的细胞致死性扩张毒素（CDT）。 cdtB 缺陷的 H。产生了肝同基因突变体（HhcdtBm7），并对其在瑞士Swiss Webster（SW）小鼠四个肠区域（空肠，回肠，盲肠和结肠）的定殖参数进行了表征。 cdtB 基因的失活消除了HhcdtBm7在感染后8周和16周（wpi）定居雌性小鼠的能力，而HhcdtBm7在8 wpi之后定居了五个雄性中的三个的全部四个肠道区域，然后被16 wpi淘汰。野生型（WT）H。在雄性和雌性小鼠的相应肠道区域分别在8和16 wpi时检测到肝。然而，WT H的定植水平。在16 wpi时，雄性小鼠的盲肠和结肠中的肝比雌性高（ P <0.0079）高约1,000倍。 WT H感染。肝，而不是HhcdtBm7，在8 wpi时与女性回肠和盲肠γ-干扰素（IFN-γ）mRNA水平显着升高相关（ P <0.016和0.031，WT H。肝炎感染的女性和假剂量的女性）。相比之下，结肠中IFN-γ的mRNA水平显着较高（ P <0.0079），而盲肠中IFN-γ的mRNA水平则较高（ P <0.15）。 HwcdtBm7克隆的雄性小鼠与假接种的对照组在8 wpi时相比。此外，在8 wpi时，对照雌性中回肠IFN-γ的mRNA水平明显高于雄性（ P <0.016）。在感染了WT H的小鼠中，与Th1相关的免疫球蛋白G2a（IgG2a），与Th2相关的IgG1和粘膜IgA的应答显着更高（分别为 P <0.002、0.002、0.002）。在16 wpi时与HhcdtBm7比较。 WT H定植的雌性和雄性小鼠在16 wpi时结肠白细胞介素10（IL-10）的表达均显着降低。 HhcdtBm7与对照组小鼠相比，肝细胞或雄性小鼠通过8 wpi瞬时定殖（ P <0.0159）。这些证据表明（i）H。肝 CDT在 H持续定居中起着至关重要的作用。肝小鼠 （ii）SW雌性小鼠对H的抵抗力更高。肝定植率高于雄性小鼠; （iii）WT H持续定植。盲肠，结肠和空肠中的肝，但仅 H的短暂定植。雌性小鼠回肠中的肝; （iv）H。肝定植与结肠IL-10产生的下调有关。

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