PDF(Pubmed)
Abstract：
Skin/soft tissue infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) pose a major healthcare burden. Distinct inflammatory and resolution phases comprise the host immune response to SSTIs. Resolution is a myeloid PPARγ-dependent anti-inflammatory phase that is essential for the clearance of MRSA. However, the signals activating PPARγ to induce resolution remain unknown. Here, we demonstrate that myeloid glucose transporter 1 (GLUT-1) is essential for the onset of resolution. MRSA-challenged macrophages are unsuccessful in generating an oxidative burst or immune radicals in the absence of GLUT-1 due to a reduction in the cellular NADPH pool. This translates in vivo as a significant reduction in lipid peroxidation products required for the activation of PPARγ in MRSA-infected mice lacking myeloid GLUT-1. Chemical induction of PPARγ during infection circumvents this GLUT-1 requirement and improves resolution. Thus, GLUT-1-dependent oxidative burst is essential for the activation of PPARγ and subsequent resolution of SSTIs.
摘要：
由耐甲氧西林金黄色葡萄球菌（MRSA）引起的皮肤/软组织感染（STTI）构成了主要的医疗保健负担。不同的炎症和消退阶段包括宿主对STTI的免疫应答。溶解是髓样PPARγ依赖性抗炎阶段，对于清除MRSA至关重要。然而,激活PPARγ诱导分辨率的信号仍然未知。这里,我们证明髓样葡萄糖转运蛋白1(GLUT-1)对于开始消退至关重要.由于细胞NADPH池的减少,在缺乏GLUT-1的情况下,MRSA攻击的巨噬细胞不能成功地产生氧化爆发或免疫自由基。这在体内转化为缺乏髓样GLUT-1的MRSA感染的小鼠中激活PPARγ所需的脂质过氧化产物的显着减少。感染期间PPARγ的化学诱导避免了这种GLUT-1要求并提高了分辨率。因此，GLUT-1依赖性的氧化爆发对于PPARγ的激活和随后的SSTI的解决是必不可少的。
