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首页> 外文期刊>Infection and immunity >Rapid Local Expression of Interleukin-12, Tumor Necrosis Factor Alpha, and Gamma Interferon after CutaneousFrancisella tularensis Infection in Tularemia-Immune Mice
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Rapid Local Expression of Interleukin-12, Tumor Necrosis Factor Alpha, and Gamma Interferon after CutaneousFrancisella tularensis Infection in Tularemia-Immune Mice

机译:Tularemia-免疫小鼠皮肤皮肤弗氏杆菌感染后白细胞介素12,肿瘤坏死因子α和γ干扰素的快速局部表达

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Francisella tularensis LVS is an effective live vaccine strain used for cutaneous vaccination against tularemia in man. In mice, injection of LVS causes invasive disease and subsequent development of immunity that is characterized by effective control of otherwise lethal doses of the organism. In the present investigation, it is shown that LVS-immune mice controlled an intradermal infection much more effectively than did naive mice; bacterial counts in skin samples were 1.5 to 2.0 log10 lower 24 h after injection and 6 log10 lower 72 h after injection in immune mice. Moreover, in contrast to naive mice, no bacteria were demonstrated in samples from livers and spleens of immune mice. By immunohistochemistry, skin samples from immune mice showed an intense staining for interleukin-12 (IL-12) and a moderate staining for tumor necrosis factor alpha (TNF-α) at 24 h postinoculation, after which staining for both cytokines faded. In naive mice, the staining for IL-12 was weak at all time points and no staining for TNF-α was observed. No staining for gamma interferon (IFN-γ) was observed in any group before 72 h. At that time point, skin samples from immune mice showed moderate staining and skin samples from naive mice showed weak staining. Reverse transcriptase PCR showed an induction of mRNA of the three cytokines in the skin within the first day after injection. A quantitative analysis demonstrated higher IFN-γ and TNF-α mRNA levels in immune mice at 24 h postinoculation. In conclusion, immunization with F. tularensis LVS conferred a capability to respond to cutaneous reinfection, with rapid local expression of IL-12, TNF-α, and IFN-γ, and this expression was paralleled by containment and mitigation of the infection. The cytokine response may be part of a local barrier function of the skin, important to host protection against tularemia.
机译: Francisella tularensis LVS是一种有效的活疫苗株,用于针对人的Tularemia进行皮肤疫苗接种。在小鼠中,注射LVS会引起侵袭性疾病,并随后产生免疫力,其特征是有效控制了该生物体的致死剂量。在本研究中,显示了LVS免疫小鼠比幼稚小鼠能更有效地控制皮内感染。免疫小鼠注射后24小时皮肤样本中细菌计数降低1.5至2.0 log 10 ,注射后72小时降低6 log 10 。而且,与幼稚的小鼠相反,在免疫小鼠的肝脏和脾脏的样品中未发现细菌。通过免疫组织化学,免疫小鼠的皮肤样本在接种后24小时显示出强烈的白介素12(IL-12)染色和中等程度的肿瘤坏死因子α(TNF-α)染色,此后两种细胞因子的染色均消失。在幼稚小鼠中,IL-12的染色在所有时间点都很弱,并且未观察到TNF-α的染色。在72小时之前的任何组中均未观察到γ干扰素(IFN-γ)染色。在那个时间点,免疫小鼠的皮肤样本显示中度染色,幼稚小鼠的皮肤样本显示弱染色。逆转录酶PCR显示在注射后第一天内皮肤中三种细胞因子的mRNA的诱导。定量分析表明,接种后24小时免疫小鼠的IFN-γ和TNF-αmRNA水平较高。总之,用 F免疫。 tularensis LVS赋予了对皮肤再感染的反应能力,IL-12,TNF-α和IFN-γ可以在局部快速表达,并且这种表达与感染的控制和缓解相平行。细胞因子反应可能是皮肤局部屏障功能的一部分,对宿主预防Tularemia至关重要。

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