Collier-Hyams L S, Neish A S
Department of Pathology, Emory University School of Medicine, 105-F Whitehead Bldg., 615 Michael St., Atlanta, Georgia 30322, USA.
Cell Mol Life Sci. 2005 Jun;62(12):1339-48. doi: 10.1007/s00018-005-5038-y.
Commensal bacteria in the lumen of the intestine exist in a mutually advantageous relationship with the mammalian host, providing benefits such as increased metabolic/digestive capabilities and exclusion of harmful microbes, and in turn receiving a nutrient-rich environment. However, in the context of a dysfunctional intestinal epithelial barrier, commensal bacteria may elicit an immune inflammatory response similar to what occurs during infection by a pathogen. Recent work has established that most eukaryotic cells possess families of receptors that can detect the structural signatures of prokaryotic life. Cells may respond to the perception of microbes by activating distinct cytoplasmic signaling cascades that ultimately result in the transcriptional activation of genes needed for proinflammatory and anti-apoptotic functions, as well as for a pro-apoptotic response. Collectively, these responses generally suffice to eliminate microbial threats and may be integral to normal intestinal homeostasis. An understanding of these mechanisms, as well as those by which microbes themselves influence intestinal epithelial responses, may help provide a new perspective on the pathogenesis of intestinal diseases.
肠道腔内的共生细菌与哺乳动物宿主存在互利关系,它们能带来诸如增强代谢/消化能力以及排斥有害微生物等益处,反过来也能获得营养丰富的环境。然而,在肠道上皮屏障功能失调的情况下,共生细菌可能引发类似于病原体感染时的免疫炎症反应。最近的研究表明,大多数真核细胞都拥有能够检测原核生物生命结构特征的受体家族。细胞可能通过激活不同的细胞质信号级联反应来应对微生物的感知,这些信号级联反应最终导致促炎和抗凋亡功能所需基因以及促凋亡反应所需基因的转录激活。总体而言,这些反应通常足以消除微生物威胁,并且可能是正常肠道稳态不可或缺的一部分。了解这些机制以及微生物自身影响肠道上皮反应的机制,可能有助于为肠道疾病的发病机制提供新的视角。