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用不同毒力的伪结核棒状杆菌菌株进行实验性感染后绵羊体内细胞因子基因的表达

Cytokine gene expression in sheep following experimental infection with various strains of Corynebacterium pseudotuberculosis differing in virulence.

作者信息

Pépin M, Seow H F, Corner L, Rothel J S, Hodgson A L, Wood P R

机构信息

Laboratoire de pathologie des petits ruminants et des abeilles, CNEVA Sophia-Antipolis, France.

出版信息

Vet Res. 1997;28(2):149-63.

PMID:9112737
Abstract

Corynebacterium pseudotuberculosis is the causative agent of caseous lymphadenitis in sheep and goats. This disease is characterized by the development of pyogranulomas in the lymph nodes and lung tissue. To measure the cytokine gene expression in C pseudotuberculosis lesions, sheep were inoculated with two attenuated strains (Tox- and PLD-t) and a wild-type (WT) strain of C pseudotuberculosis and were necropsied at 7 or 28 days post-inoculation. The Tox- strain showed a strong reduction in virulence as assessed by the absence of disseminating lesions in the lymph nodes draining the inoculation site in contrast with the WT strain. The PLD-t strain showed an intermediate reduction in virulence. The two attenuated strains, however, induced the same amount of antibodies and IFN-gamma production as the WT strain. Using a semi-quantitative RT-PCR technique, the expression of inflammatory cytokines was found to be higher in the inoculation site, whereas expression of T-cell associated cytokines was more intense in the draining lymph node. On the whole, the infected sheep produced high levels of cytokines in at least one organ on days 7 or 28 post-inoculation. No significant differences in cytokine gene expression were shown between sheep infected with strains differing in virulence. Higher cytokine expression was measured in sheep with pyogranulomas in the draining lymph nodes as compared to those without, especially for interleukin-1 beta and interleukin-8. Overall, these results taken together confirmed the attenuation of virulence in Tox- and PLD-t strains of C pseudotuberculosis and showed the important role of PLD in disseminating the bacteria from the inoculation site to the draining lymph nodes. The pathogenesis of ovine caseious lymphadenitis was shown to be associated with production of cytokines at the pyogranuloma level, but the local cytokine patterns associated with different courses of infection were not distinguished.

摘要

伪结核棒状杆菌是绵羊和山羊干酪性淋巴结炎的病原体。这种疾病的特征是在淋巴结和肺组织中形成脓性肉芽肿。为了测量伪结核棒状杆菌病变中细胞因子基因的表达,给绵羊接种了两种减毒株(Tox-和PLD-t)以及一株伪结核棒状杆菌野生型(WT)菌株,并在接种后7天或28天进行剖检。与WT菌株相比,Tox-菌株的毒力显著降低,接种部位引流淋巴结中未见播散性病变。PLD-t菌株的毒力呈中等程度降低。然而,这两种减毒株诱导产生的抗体量和IFN-γ与WT菌株相同。使用半定量RT-PCR技术发现,炎症细胞因子在接种部位的表达较高,而T细胞相关细胞因子在引流淋巴结中的表达更为强烈。总体而言,感染的绵羊在接种后7天或28天至少在一个器官中产生了高水平的细胞因子。感染不同毒力菌株的绵羊之间细胞因子基因表达未显示出显著差异。与无干酪性肉芽肿的绵羊相比,引流淋巴结中有干酪性肉芽肿的绵羊细胞因子表达更高,尤其是白细胞介素-1β和白细胞介素-8。总体而言,这些结果共同证实了伪结核棒状杆菌Tox-和PLD-t菌株的毒力减弱,并表明PLD在将细菌从接种部位传播到引流淋巴结中起重要作用。绵羊干酪性淋巴结炎的发病机制被证明与脓性肉芽肿水平的细胞因子产生有关,但未区分与不同感染过程相关的局部细胞因子模式。

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