Netea Mihai G, Ferwerda Gerben, de Jong Dirk J, Jansen Trees, Jacobs Liesbeth, Kramer Matthijs, Naber Ton H J, Drenth Joost P H, Girardin Stephen E, Kullberg Bart Jan, Adema Gosse J, Van der Meer Jos W M
Department of Medicine, Radboud University Medical Center Nijmegen, The Netherlands.
J Immunol. 2005 May 15;174(10):6518-23. doi: 10.4049/jimmunol.174.10.6518.
The recognition of peptidoglycan by cells of the innate immune system has been controversial; both TLR2 and nucleotide-binding oligomerization domain-2 (NOD2) have been implicated in this process. In the present study we demonstrate that although NOD2 is required for recognition of peptidoglycan, this leads to strong synergistic effects on TLR2-mediated production of both pro- and anti-inflammatory cytokines. Defective IL-10 production in patients with Crohn's disease bearing loss of function mutations of NOD2 may lead to overwhelming inflammation due to a subsequent Th1 bias. In addition to the potentiation of TLR2 effects, NOD2 is a modulator of signals transmitted through TLR4 and TLR3, but not through TLR5, TLR9, or TLR7. Thus, interaction between NOD2 and specific TLR pathways may represent an important modulatory mechanism of innate immune responses.
天然免疫系统细胞对肽聚糖的识别一直存在争议；Toll样受体2（TLR2）和核苷酸结合寡聚化结构域2（NOD2）都与这一过程有关。在本研究中，我们证明，虽然识别肽聚糖需要NOD2，但这会对TLR2介导的促炎和抗炎细胞因子的产生产生强烈的协同效应。患有克罗恩病且携带功能丧失性NOD2突变的患者，其白细胞介素-10产生缺陷，可能会因随后的Th1偏向而导致炎症失控。除了增强TLR2的作用外，NOD2还是通过TLR4和TLR3（而非TLR5、TLR9或TLR7）传递的信号的调节剂。因此，NOD2与特定TLR途径之间的相互作用可能代表了天然免疫反应的一种重要调节机制。
