Mueller Tobias, Podolsky Daniel K
Gastrointestinal Unit, Department of Medicine, Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, Massachusetts, USA.
Curr Opin Gastroenterol. 2005 Jul;21(4):419-25.
Chronic inflammatory bowel diseases appear to result from inappropriate immune responses driven by apparently normal intestinal microflora in genetically susceptible hosts. This review focuses on recently described mechanisms balancing toll-like receptor and nucleotide-binding-oligomerization domain activation in the face of ubiquitous enteric flora.
Toll-like receptor and nucleotide-binding-oligomerization domain signaling plays an integral role in the close collaboration between the intestinal epithelial cell monolayer and adjacent mucosal immune cells. Pathways activated by functional cytosolic nucleotide-binding-oligomerization domain proteins appear to interact with those mediated by membrane-associated toll-like receptors in the innate and adaptive immune defense against intra-and extracellular pathogens. Nucleotide-binding-oligomerization domain-mediated signaling may also control toll-like receptor-induced proinflammatory pathways.
Intersections between toll-like receptor and nucleotide-binding-oligomerization domain pathways may exist to refine the host immune response to pathogens and prevent undesired immune stimulation driven by the intestinal microbiota. Deficient toll-like receptor and nucleotide-binding-oligomerization domain function due to genetic variability is associated with an increased susceptibility to the development of inflammatory bowel disease.
慢性炎症性肠病似乎是由基因易感宿主中看似正常的肠道微生物群驱动的不适当免疫反应所致。本综述重点关注近期描述的在面对无处不在的肠道菌群时平衡Toll样受体和核苷酸结合寡聚化结构域激活的机制。
Toll样受体和核苷酸结合寡聚化结构域信号传导在肠上皮细胞单层与相邻黏膜免疫细胞之间的密切协作中发挥着不可或缺的作用。功能性胞质核苷酸结合寡聚化结构域蛋白激活的通路似乎在针对细胞内和细胞外病原体的固有免疫和适应性免疫防御中与膜相关Toll样受体介导的通路相互作用。核苷酸结合寡聚化结构域介导的信号传导也可能控制Toll样受体诱导的促炎通路。
Toll样受体和核苷酸结合寡聚化结构域通路之间可能存在交叉，以优化宿主对病原体的免疫反应，并防止由肠道微生物群驱动的不必要的免疫刺激。由于基因变异导致的Toll样受体和核苷酸结合寡聚化结构域功能缺陷与炎症性肠病发生易感性增加有关。
