Glucose transporter 1 is essential for the resolution of methicillin-resistant S. aureus skin and soft tissue infections

Autor: Srijon K. Banerjee, Lance R. Thurlow, Kartik Kannan, Anthony R. Richardson
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Cell Reports, Vol 43, Iss 7, Pp 114486- (2024)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2024.114486
Popis: Summary: 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.
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