Host-based lipid inflammation drives pathogenesis in &ITFrancisella&IT infection
Host-based lipid inflammation drives pathogenesis in &ITFrancisella&IT infection
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DOI：
10.1073/pnas.1712887114
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发表时间：
2017-11-21
影响因子：
11.1
通讯作者：
Ernst, Robert K.
中科院分区：
文献类型：
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作者：
Scott, Alison J.;Post, Julia Maria;Ernst, Robert K.
质谱成像（MSI）用于阐明宿主脂质参与感染性细菌感染期间宿主-病原体界面产生的炎症信号通路。以新弗朗西斯菌为模式生物，对小鼠组织中参与脾反应的宿主磷脂和细菌脂质毒力因子（内毒素）进行了成像和鉴定。在这里，我们展示了内毒素在致死性小鼠新乳杆菌感染模型中的检测和分布，以及使用MSI在2D和3D渲染中确定时间和空间解决的先天脂质炎症反应。此外，我们发现环氧化酶-2依赖的脂质炎症途径是导致新乳杆菌感染致死的原因，因为包括前列腺素E2在内的促炎效应物过量产生。这项研究的结果强调，宿主脂质成分的空间测定对于确定有效解决由细菌、真菌和病毒起源的高致病性和致死性感染的新策略至关重要。
Mass spectrometry imaging (MSI) was used to elucidate host lipids involved in the inflammatory signaling pathway generated at the host-pathogen interface during a septic bacterial infection. Using Francisella novicida as a model organism, a bacterial lipid virulence factor (endotoxin) was imaged and identified along with host phospholipids involved in the splenic response in murine tissues. Here, we demonstrate detection and distribution of endotoxin in a lethal murine F. novicida infection model, in addition to determining the temporally and spatially resolved innate lipid inflammatory response in both 2D and 3D renderings using MSI. Further, we show that the cyclooxygenase-2-dependent lipid inflammatory pathway is responsible for lethality in F. novicida infection due to overproduction of proinflammatory effectors including prostaglandin E2. The results of this study emphasize that spatial determination of the host lipid components of the immune response is crucial to identifying novel strategies to effectively address highly pathogenic and lethal infections stemming from bacterial, fungal, and viral origins.