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首页> 外文期刊>Infection and immunity >Attenuated Yersinia enterocolitica Mutant Strains Exhibit Differential Virulence in Cytokine-Deficient Mice: Implications for the Development of Novel Live Carrier Vaccines
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Attenuated Yersinia enterocolitica Mutant Strains Exhibit Differential Virulence in Cytokine-Deficient Mice: Implications for the Development of Novel Live Carrier Vaccines

机译：减毒小肠结肠炎耶尔森氏菌突变株在细胞因子缺乏小鼠中表现出差异毒力：新型活载体疫苗的发展的影响。

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Yersinia enterocolitica mutant strains, including mutants deficient in the chaperone SycH resulting in a functional deficiency in tyrosine phosphatase (YopH), Mn-cofactored superoxide dismutase (SodA), iron-repressive protein 1 (IRP-1), and Yersinia adhesin A (YadA), were demonstrated to be highly attenuated in wild-type C57BL/6 mice. TNFRp55?/?, IL-12p40?/?, and IL-18?/? mutant mice, in which the Yersinia wild-type strain causes severe systemic infections, were used to investigate whether these Yersinia mutant strains would be attenuated in immunodeficient hosts. A plasmid-cured Yersinia mutant strain was unable to colonize any of the mutant mice tested. A SycH-deficient mutant strain colonized intestinal tissues of these mice but was attenuated for systemic infection in all of the mutant mice. Both YadA- and Irp-1-deficient Yersinia mutants were still attenuated in IL-12?/? and IL-18?/? mice but were pathogenic in TNFRp55?/? mice. By contrast, a Yersinia sodA mutant was highly pathogenic for TNFRp55?/? and IL-12p40?/? mice while interleukin-18 (IL-18) was dispensable. This finding demonstrates that certain virulence factors enable yersiniae to compete with distinct cytokine-dependent host defense mechanisms. Moreover, while gamma interferon mRNA expression did not reflect protective host responses in cytokine-deficient mice, IL-10 expression coincided with a heavy splenic bacterial load and was associated with progressive infection courses. We can thus segregate minor (SodA), intermediate (YadA and IRP-1), and major (YopH) virulence factors of Y. enterocolitica. Finally, we demonstrate that, even in immunocompromised hosts, Yersinia sycH and, with some restrictions, irp-1 mutants may be suitable for use as live carrier vaccines.
机译：耶尔森氏菌 肠结肠炎突变株，包括缺乏伴侣蛋白SycH的突变株，导致酪氨酸磷酸酶（YopH），Mn辅助超氧化物歧化酶（SodA），铁抑制性功能缺陷蛋白1（IRP-1）和耶尔森氏菌黏附素A（YadA）被证明在野生型C57BL / 6小鼠中高度减毒。 TNFRp55 ？/？，IL-12p40 ？/？和IL-18 ？/？突变小鼠，其中耶尔森氏菌野生型菌株引起严重的全身感染，用于研究这些耶尔森氏菌突变株是否会在免疫缺陷宿主中减毒。质粒固化的耶尔森氏菌突变株无法在任何测试的突变小鼠中定殖。 SycH缺陷突变株定植在这些小鼠的肠道组织中，但在所有突变小鼠中均因全身感染而减毒。 IL-12 ？/？和IL-18 ？/？小鼠的YadA缺陷型和Irp-1缺陷型耶尔森氏菌仍然减毒。但在TNFRp55 ？/？小鼠中具有致病性。相比之下，耶尔森氏菌 sodA 突变体对TNFRp55 ？/？和IL-12p40 ？/？具有高致病性。白介素-18（IL-18）是可有可无的。该发现表明某些毒力因子使耶尔森氏菌能够与独特的依赖细胞因子的宿主防御机制竞争。此外，虽然γ干扰素mRNA的表达不能反映细胞因子缺乏小鼠的保护性宿主反应，但IL-10的表达与脾脏细菌负荷重有关，并且与进行性感染过程有关。因此，我们可以分离 Y 的次要（SodA），中间（YadA和IRP-1）和主要（YopH）毒力因子。 enterocolitica 。最后，我们证明，即使在免疫功能低下的宿主中，耶尔森氏菌 sycH 和在某些限制下， irp-1 突变体也可能适合用作活载体疫苗。

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