Endotoxin pretreatment improves bacterial clearance and decreases mortality in mice challenged with Staphylococcus aureus
Endotoxin pretreatment improves bacterial clearance and decreases mortality in mice challenged with Staphylococcus aureus
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DOI：
10.1097/shk.0b013e318150776f
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发表时间：
2008-04-01
期刊：
影响因子：
3.1
通讯作者：
Sherwood, Edward R.
中科院分区：
文献类型：
--
作者：
Murphey, E. D.;Fang, Geping;Sherwood, Edward R.
我们研究了大肠杆菌衍生的LPS诱导的耐受性对随后的金黄色葡萄球菌细菌挑战的先天免疫应答的影响。通过连续2天腹膜内或静脉内注射2 μ g LPS在野生型小鼠中诱导LIPS耐受性。小鼠用静脉注射活S.金黄色葡萄球菌（5 × 10（8）集落形成单位）2天后，第二次LPS剂量。LPS耐受小鼠对细菌攻击的血清干扰素-γ反应减弱。与盐水预处理的对照小鼠相比，LPS耐受小鼠在葡萄球菌攻击后肝和脾组织中的细菌计数减少，存活率提高。通过静脉途径的LIPS预处理也与肺组织中除肝脏和脾脏外的细菌菌落数量减少相关，这表明在腹膜内LPS预处理后LPS耐受的诱导在一定程度上是区室化的。耐受性的诱导似乎是由于LPS特异性信号传导，因为LPS非应答C3 H/HeJ小鼠的LIPS预处理在细菌攻击后没有提供类似的效果。从LPS耐受小鼠脾脏的流式细胞术分析显示，与对照小鼠相比，吞噬细胞（中性粒细胞和巨噬细胞）的增加。LPS耐受小鼠脾细胞的离体培养表明，异硫氰酸荧光素标记的卵清蛋白的摄取增加，但在异硫氰酸荧光素标记的葡萄球菌的吞噬作用或杀菌活性没有差异，可以证明在每个细胞的基础上。这些结果表明，LPS耐受期间炎症和死亡率的减弱延伸到革兰氏阳性细菌生物体，并表明LPS诱导的先天免疫应答的增强可能归因于吞噬细胞数量的增加。
We studied the effects of tolerance induced by Escherichia coli-derived LPS on the innate immune response to a subsequent Staphylococcus aureus bacterial challenge. LIPS tolerance was induced in wild-type mice by either intraperitoneal or intravenous injection of 2 mu g of LPS on 2 consecutive days. Mice were challenged with an intravenous injection of live S. aureus (5 x 10(8) colony-forming units) 2 days after the second LPS dose. LPS-tolerant mice had a diminished serum interferon-gamma response to the bacterial challenge. Bacterial counts in liver and spleen tissues were decreased, and survival was improved after the Staphylococcus challenge in LPS-tolerant mice compared with saline-pretreated control mice. LIPS pretreatment by the intravenous route was also associated with a decreased number of bacterial colonies in lung tissue in addition to liver and spleen, suggesting that induction of LPS tolerance was somewhat compartmentalized after intraperitoneal LPS pretreatment. Induction of tolerance seemed to be due to LIPS-specific signaling because LIPS pretreatment of LPS-non responsive C3H/HeJ mice did not provide similar effects after bacterial challenge. Flow cytometric analysis of spleens from LPS-tolerant mice revealed an increase in phagocytic cells (neutrophils and macrophages) compared with control mice. Ex vivo culture of splenocytes from LPS-tolerant mice demonstrated increased uptake of fluorescein isothiocyanate-tagged ovalbumin, but no difference in either phagocytosis of fluorescein isothiocyanate-labeled Staphylococcus or bactericidal activity could be demonstrated on a per-cell basis. These results show that attenuation of inflammation and mortality during LPS tolerance extends to gram-positive bacterial organisms and suggests that LPS-induced enhancement of the innate immune response may be attributed to increased numbers of phagocytic cells.