McDermott Michael F, Tschopp Jürg
Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds LS9 7TF, UK.
Trends Mol Med. 2007 Sep;13(9):381-8. doi: 10.1016/j.molmed.2007.07.005. Epub 2007 Sep 5.
Pattern-recognition receptors, such as Toll-like receptors and NOD-like receptors (NLRs), are able through the recognition of pathogen-associated molecular patterns and danger-associated molecular patterns to sense microbe-dependent and microbe-independent danger and thereby initiate innate immune responses. In some autoinflammatory conditions, abnormalities in NLR signaling pathways are involved in pathogenesis, as exemplified by NOD2 mutations associated with Crohn's disease. Some other NLRs are components of the inflammasome, a caspase-1- and prointerleukin-1beta-activating complex. Clinical and experimental studies are beginning to reveal the central role of the inflammasome in innate immunity. Here, we focus on monogenic hereditary inflammatory diseases, such as Muckle-Wells syndrome, which are associated with mutations in proteins that modulate the activity of the inflammasome, and on some multifactorial disorders, such as Type 2 diabetes and hypertension.
模式识别受体，如Toll样受体和NOD样受体（NLRs），能够通过识别病原体相关分子模式和危险相关分子模式来感知微生物依赖性和非微生物依赖性危险，从而启动先天性免疫反应。在一些自身炎症性疾病中，NLR信号通路异常参与发病机制，如与克罗恩病相关的NOD2突变。其他一些NLRs是炎性小体的组成部分，炎性小体是一种激活半胱天冬酶-1和白细胞介素-1β前体的复合物。临床和实验研究开始揭示炎性小体在先天性免疫中的核心作用。在此，我们重点关注单基因遗传性炎症性疾病，如与调节炎性小体活性的蛋白质突变相关的穆克-韦尔斯综合征，以及一些多因素疾病，如2型糖尿病和高血压。
