Ahmed Duale, Al-Daraawi Malak, Cassol Edana
Department of Health Sciences, Carleton University, Ottawa, Ontario, Canada.
Department of Biology, Carleton University, Ottawa, Ontario, Canada.
J Leukoc Biol. 2023 Feb 1;113(2):164-190. doi: 10.1093/jleuko/qiac011.
Several studies over the last decade have identified intimate links between cellular metabolism and macrophage function. Metabolism has been shown to both drive and regulate macrophage function by producing bioenergetic and biosynthetic precursors as well as metabolites (and other bioactive molecules) that regulate gene expression and signal transduction. Many studies have focused on lipopolysaccharide-induced reprogramming, assuming that it is representative of most inflammatory responses. However, emerging evidence suggests that diverse pathogen-associated molecular patterns (PAMPs) are associated with unique metabolic profiles, which may drive pathogen specific immune responses. Further, these metabolic pathways and processes may act as a rheostat to regulate the magnitude of an inflammatory response based on the biochemical features of the local microenvironment. In this review, we will discuss recent work examining the relationship between cellular metabolism and macrophage responses to viral PAMPs and describe how these processes differ from lipopolysaccharide-associated responses. We will also discuss how an improved understanding of the specificity of these processes may offer new insights to fine-tune macrophage function during viral infections or when using viral PAMPs as therapeutics.
在过去十年中，多项研究已经确定了细胞代谢与巨噬细胞功能之间的密切联系。代谢已被证明通过产生生物能量和生物合成前体以及调节基因表达和信号转导的代谢物（和其他生物活性分子）来驱动和调节巨噬细胞功能。许多研究集中在脂多糖诱导的重编程上，假设它代表了大多数炎症反应。然而，新出现的证据表明，多种病原体相关分子模式（PAMP）与独特的代谢谱相关，这可能驱动病原体特异性免疫反应。此外，这些代谢途径和过程可能充当变阻器，根据局部微环境的生化特征调节炎症反应的强度。在这篇综述中，我们将讨论最近研究细胞代谢与巨噬细胞对病毒PAMP反应之间关系的工作，并描述这些过程与脂多糖相关反应有何不同。我们还将讨论如何更好地理解这些过程的特异性，可能为在病毒感染期间或使用病毒PAMP作为治疗手段时微调巨噬细胞功能提供新的见解。
