Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
BMC Immunol. 2010 Jun 16;11:29. doi: 10.1186/1471-2172-11-29.
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.
鼠疫耶尔森菌是肺鼠疫的病原体；最近，我们和其他人报告称，在肺部感染鼠疫耶尔森菌后的前 24-36 小时内，肺部组织中无法检测到促炎细胞因子的表达。
在这里，我们报告称，CO92 delta yopH 突变体鼻内感染小鼠会导致肺部早期的促炎反应，特征是感染后 24 小时促炎细胞因子肿瘤坏死因子-α和白细胞介素-1β增加。CO92 delta yopH 定植于肺部，但不会传播到肝脏或脾脏，并在感染后 72 小时内从宿主中清除。这与野生型 CO92 感染观察到的情况不同，在野生型 CO92 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。CO92 迅速传播到肝脏和脾脏，导致这些组织中的细菌负荷很高，最终在感染后 72-94 小时导致死亡。TNF-α 缺陷小鼠对 CO92 delta yopH 感染的易感性更高，有 40%的小鼠死于感染。
总之，我们的结果表明，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一个重要步骤。
