Wang Andrew, Huen Sarah C, Luan Harding H, Yu Shuang, Zhang Cuiling, Gallezot Jean-Dominique, Booth Carmen J, Medzhitov Ruslan
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Medicine (Rheumatology), Yale University School of Medicine, New Haven, CT 06520, USA.
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Medicine (Nephrology), Yale University School of Medicine, New Haven, CT 06520, USA.
Cell. 2016 Sep 8;166(6):1512-1525.e12. doi: 10.1016/j.cell.2016.07.026.
Acute infections are associated with a set of stereotypic behavioral responses, including anorexia, lethargy, and social withdrawal. Although these so-called sickness behaviors are the most common and familiar symptoms of infections, their roles in host defense are largely unknown. Here, we investigated the role of anorexia in models of bacterial and viral infections. We found that anorexia was protective while nutritional supplementation was detrimental in bacterial sepsis. Furthermore, glucose was necessary and sufficient for these effects. In contrast, nutritional supplementation protected against mortality from influenza infection and viral sepsis, whereas blocking glucose utilization was lethal. In both bacterial and viral models, these effects were largely independent of pathogen load and magnitude of inflammation. Instead, we identify opposing metabolic requirements tied to cellular stress adaptations critical for tolerance of differential inflammatory states. VIDEO ABSTRACT.
急性感染与一系列刻板的行为反应相关，包括厌食、嗜睡和社交退缩。尽管这些所谓的疾病行为是感染最常见和为人熟知的症状，但其在宿主防御中的作用在很大程度上尚不清楚。在此，我们研究了厌食在细菌和病毒感染模型中的作用。我们发现，厌食具有保护作用，而在细菌性败血症中营养补充是有害的。此外，葡萄糖对于这些效应是必需且充分的。相比之下，营养补充可预防流感感染和病毒性败血症导致的死亡，而阻断葡萄糖利用则是致命的。在细菌和病毒模型中，这些效应在很大程度上与病原体载量和炎症程度无关。相反，我们确定了与细胞应激适应相关的相反代谢需求，这些适应对于耐受不同的炎症状态至关重要。视频摘要。
