YopH inhibits early pro-inflammatory cytokine responses during plague pneumonia.
YopH inhibits early pro-inflammatory cytokine responses during plague pneumonia.
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DOI：
10.1186/1471-2172-11-29
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发表时间：
2010-06-16
期刊：
影响因子：
3
通讯作者：
Dube PH
中科院分区：
文献类型：
--
作者：
Cantwell AM;Bubeck SS;Dube PH
鼠疫耶尔森氏菌是肺鼠疫的病原体，最近，我们和其他人报道，在肺部感染鼠疫耶尔森氏菌后的最初24-36小时内，肺组织中检测不到鼠疫促炎细胞因子表达。在这里，我们报告说，小鼠鼻内感染CO 92 δ yopH突变体导致肺部早期促炎反应，其特征在于感染后24小时促炎细胞因子肿瘤坏死因子-α和白细胞介素1-β增加。CO 92 δ yopH定殖于肺，但不扩散到肝或脾，并在感染后72小时内从宿主中清除。这与在野生型CO 92感染中观察到的情况不同，在野生型CO 92感染中，直到感染后36-48小时才检测到促炎细胞因子表达和免疫细胞浸润到肺部。CO 92迅速传播到肝脏和脾脏，导致这些组织中的高细菌负荷，最终在感染后72-94小时累积死亡。缺乏TNF-α的小鼠更容易受到CO 92 δ yopH感染，40%的小鼠死于感染。总之，我们的研究结果表明，YopH可以抑制小鼠肺部的早期促炎反应，这是感染发病机制中的重要一步。
Yersinia pestis is the causative agent of pneumonic plague; recently, we and others reported that during the first 24-36 hours after pulmonary infection with Y. pestis pro-inflammatory cytokine expression is undetectable in lung tissues. Here, we report that, intranasal infection of mice with CO92 delta yopH mutant results in an early pro-inflammatory response in the lungs characterized by an increase in the pro-inflammatory cytokines Tumor Necrosis Factor-alpha and Interleukin one-beta 24 hours post-infection. CO92 delta yopH colonizes the lung but does not disseminate to the liver or spleen and is cleared from the host within 72 hours post-infection. This is different from what is observed in a wild-type CO92 infection, where pro-inflammatory cytokine expression and immune cell infiltration into the lungs is not detectable until 36-48 h post-infection. CO92 rapidly disseminates to the liver and spleen resulting in high bacterial burdens in these tissues ultimately cumulating in death 72-94 h post-infection. Mice deficient in TNF-alpha are more susceptible to CO92 delta yopH infection with 40% of the mice succumbing to infection. Altogether, our results suggest that YopH can inhibit an early pro-inflammatory response in the lungs of mice and that this is an important step in the pathogenesis of infection.
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影响因子：
3.1
作者：
Dube, PH;Handley, SA;Miller, VL
通讯作者：
Miller, VL
影响因子：
3.1
作者：
Bubeck, Sarah S.;Cantwell, Angelene M.;Dube, Peter H.
通讯作者：
Dube, Peter H.
影响因子：
3.6
作者：
Darwin, AJ;Miller, VL
通讯作者：
Miller, VL
影响因子：
64.8
作者：
Barton, Erik S.;White, Douglas W.;Virgin, Herbert W.
通讯作者：
Virgin, Herbert W.
影响因子：
3.1
作者：
Dube, PH;Handley, SA;Miller, VL
通讯作者：
Miller, VL