Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
J Allergy Clin Immunol. 2013 Aug;132(2):287-94. doi: 10.1016/j.jaci.2013.06.022.
Pathogen and nutrient response pathways are evolutionarily conserved and highly integrated to regulate metabolic and immune homeostasis. Excessive nutrients can be sensed by innate pattern recognition receptors as danger signals either directly or through production of endogenous ligands or modulation of intestinal microbiota. This triggers the activation of downstream inflammatory cascades involving nuclear factor κB and mitogen-activated protein kinase and ultimately induces the production of inflammatory cytokines and immune cell infiltration in various metabolic tissues. The chronic low-grade inflammation in the brain, islet, liver, muscle, and adipose tissue further promotes insulin resistance, energy imbalance, and impaired glucose/lipid metabolism, contributing to the metabolic complications of obesity, such as diabetes and atherosclerosis. In addition, innate pathogen receptors have now emerged as a critical link between the intestinal microbiota and host metabolism. In this review we summarize recent studies demonstrating the important roles of innate pathogen receptors, including Toll-like receptors, nucleotide oligomerization domain containing proteins, and inflammasomes in mediating the inflammatory response to metabolic stress in different tissues and highlight the interaction of innate pattern recognition receptors, gut microbiota, and nutrients during the development of obesity and related metabolic disorders.
病原体和营养响应途径在进化上是保守的，并且高度集成，以调节代谢和免疫稳态。过多的营养物质可以通过先天模式识别受体直接或通过内源性配体的产生或肠道微生物群的调节来感知为危险信号。这会触发下游炎症级联反应的激活，涉及核因子 κB 和丝裂原激活蛋白激酶，最终导致各种代谢组织中炎症细胞因子的产生和免疫细胞浸润。大脑、胰岛、肝脏、肌肉和脂肪组织中的慢性低度炎症进一步促进胰岛素抵抗、能量失衡和葡萄糖/脂质代谢受损，导致肥胖的代谢并发症，如糖尿病和动脉粥样硬化。此外，先天病原体受体现已成为肠道微生物群和宿主代谢之间的关键联系。在这篇综述中，我们总结了最近的研究，这些研究表明先天病原体受体（包括 Toll 样受体、核苷酸寡聚化结构域包含蛋白和炎性小体）在介导不同组织对代谢应激的炎症反应方面的重要作用，并强调了先天模式识别受体、肠道微生物群和营养物质在肥胖和相关代谢紊乱发展过程中的相互作用。
