Septic mice are susceptible to pulmonary aspergillosis
Septic mice are susceptible to pulmonary aspergillosis
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DOI：
10.1016/s0002-9440(10)63615-2
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发表时间：
2003-12-01
影响因子：
6
通讯作者：
Kunkel, SL
中科院分区：
文献类型：
--
作者：
Benjamim, CF;Hogaboam, CM;Kunkel, SL
临床数据强调了这样一个事实，即在急性脓毒症发作后存活的患者随后发生高死亡率。在此，我们描述了一种临床相关的实验性脓毒症模型，我们相信这将允许进一步研究脓毒症后肺部先天免疫应答的调节方式。对C57 BL/6小鼠进行盲肠结扎和穿刺（CLP）模型，其中盲肠被部分结扎并用21号针穿刺9次。该手术与术后3天的100%死亡率相关。相反，当CLP小鼠在术后8小时开始用抗生素治疗，此后每12小时用抗生素治疗一次，直到第3天，近似60%的小鼠存活。有趣的是，CLP存活者在CLP后第3天用活的烟曲霉分生孢子进行肠道内攻击时迅速死于肺部感染（100%死亡率）。在分生孢子攻击的假手术小鼠中未观察到死亡。先天性免疫应答缺陷的A. CLP小鼠中的烟曲霉菌感染不能用中性粒细胞浸润肺部的失败来解释。相反，基因阵列分析显示，先天免疫反应的几个组成部分，包括核因子-kB信号通路，被下调。因此，我们描述了一个系统的脓毒症诱导的先天性免疫功能衰竭的C57 BL/6小鼠的肺部。
Clinical data underscores the fact that subsequent high mortality rates occur in patients who survive acute septic episodes. Herein, we described a clinically relevant model of experimental sepsis that we believe will allow further investigation of the manner in which the pulmonary innate immune response is modulated after sepsis. C57BL/6 Mice were subjected to cecal ligation and puncture (CLP) model, whereby the cecum was partially ligated and punctured nine times with a 21-gauge needle. This procedure was associated with 100% mortality at 3 days after surgery. In contrast, when mice subjected to CLP were treated with antibiotic beginning at 8 hours after surgery, and every 12 hours thereafter until 3 days, similar to60% of the mice survived. Interestingly, CLP survivors quickly succumbed (100% mortality) to pulmonary infection when intratracheally challenged, at day 3 after CLP, with viable Aspergillus fumigatus conidia. No mortality was observed in conidia-challenged sham-operated mice. The defective innate immune response against A. fumigatus in CLP mice could not be explained by a failure of neutrophils to infiltrate the lungs. Instead, gene array analysis revealed that several components of the innate immune response, including the nuclear factor-kB signaling pathway, were down-regulated. Thus, we describe a system of sepsis-induced innate immune failure in the lungs of C57BL/6 mice.