ABSTRACT

Nutrients not only act as building blocks but also as signaling molecules. Nutrient-availability promotes cell growth and proliferation and suppresses catabolic processes, such as macroautophagy/autophagy. These effects are mediated by checkpoint kinases such as MTOR (mechanistic target of rapamycin kinase), which is activated by amino acids and growth factors, and AMP-activated protein kinase (AMPK), which is activated by low levels of glucose or ATP. These kinases have wide-ranging activities that can be co-opted by immune cells upon exposure to danger signals, cytokines or pathogens. Here, we discuss recent insight into the regulation and repurposing of nutrient-sensing responses by the innate immune system during infection. Moreover, we examine how natural mutations and pathogen-mediated interventions can alter the balance between anabolic and autophagic pathways leading to a breakdown in tissue homeostasis and/or host defense.

Abbreviations: AKT1/PKB: AKT serine/threonine kinase 1; ATG: autophagy related; BECN1: beclin 1; CGAS: cyclic GMP-AMP synthase; EIF2AK4/GCN2: eukaryotic translation initiation factor 2 alpha kinase 4; ER: endoplasmic reticulum; FFAR: free fatty acid receptor; GABARAP: GABA type A receptor-associated protein; IFN: interferon; IL: interleukin; LAP: LC3-associated phagocytosis; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAP3K7/TAK1: mitogen-activated protein kinase kinase kinase 7; MAPK: mitogen-activated protein kinase; MTOR: mechanistic target of rapamycin kinase; NLR: NOD (nucleotide-binding oligomerization domain) and leucine-rich repeat containing proteins; PI3K, phosphoinositide 3-kinase; PRR: pattern-recognition receptor; PtdIns3K: phosphatidylinositol 3-kinase; RALB: RAS like proto-oncogene B; RHEB: Ras homolog, MTORC1 binding; RIPK1: receptor interacting serine/threonine kinase 1; RRAG: Ras related GTP binding; SQSTM1/p62: sequestosome 1; STING1/TMEM173: stimulator of interferon response cGAMP interactor 1; STK11/LKB1: serine/threonine kinase 11; TBK1: TANK binding kinase 1; TLR: toll like receptor; TNF: tumor necrosis factor; TRAF6: TNF receptor associated factor 6; TRIM: tripartite motif protein; ULK1: unc-51 like autophagy activating kinase 1; V-ATPase: vacuolar-type H⁺-proton-translocating ATPase.

摘要

营养素不仅充当构件，而且充当信号分子。营养利用率促进细胞生长和增殖并抑制分解代谢过程，例如巨自噬/自噬。这些作用由检查点激酶介导，例如由氨基酸和生长因子激活的 MTOR（雷帕霉素激酶的机械靶标）和由低水平葡萄糖或 ATP 激活的 AMP 活化蛋白激酶 (AMPK)。这些激酶具有广泛的活性，可以在暴露于危险信号、细胞因子或病原体时被免疫细胞吸收。在这里，我们讨论了最近对感染期间先天免疫系统对营养感应反应的调节和再利用的见解。而且，

缩写：AKT1/PKB：AKT丝氨酸/苏氨酸激酶1；ATG：自噬相关；BECN1：beclin 1；CGAS：环状 GMP-AMP 合酶；EIF2AK4/GCN2：真核翻译起始因子 2 α 激酶 4；ER：内质网；FFAR：游离脂肪酸受体；GABARAP：GABA A 型受体相关蛋白；干扰素：干扰素；IL：白细胞介素；LAP：LC3相关的吞噬作用；MAP1LC3B/LC3B：微管相关蛋白1轻链3β；MAP3K7/TAK1：丝裂原活化蛋白激酶激酶激酶 7；MAPK：丝裂原活化蛋白激酶；MTOR：雷帕霉素激酶的机制靶点；NLR：NOD（核苷酸结合寡聚结构域）和富含亮氨酸重复的蛋白质；PI3K，磷酸肌醇 3-激酶；PRR：模式识别受体；PtdIns3K：磷脂酰肌醇 3-激酶；RALB：RAS样原癌基因B；RHEB：Ras 同源物，MTORC1 结合；RIPK1：受体相互作用的丝氨酸/苏氨酸激酶 1；RRAG：Ras 相关的 GTP 结合；SQSTM1/p62：隔离体 1；STING1/TMEM173：干扰素反应 cGAMP 相互作用子 1 的刺激物；STK11/LKB1：丝氨酸/苏氨酸激酶 11；TBK1：TANK结合激酶1；TLR：toll样受体；TNF：肿瘤坏死因子；TRAF6：TNF受体相关因子6；TRIM：三方基序蛋白；ULK1：unc-51 样自噬激活激酶 1；V-ATP酶：液泡型H unc-51 样自噬激活激酶 1；V-ATP酶：液泡型H unc-51 样自噬激活激酶 1；V-ATP酶：液泡型H⁺ -质子转运ATP酶。