Laboratory of Intracellular Parasites and Research Technologies Branch, Microscopy Unit, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
Proc Natl Acad Sci U S A. 2010 Oct 12;107(41):17733-8. doi: 10.1073/pnas.1006098107. Epub 2010 Sep 27.
Salmonella enterica is an intracellular bacterial pathogen that resides and proliferates within a membrane-bound vacuole in epithelial cells of the gut and gallbladder. Although essential to disease, how Salmonella escapes from its intracellular niche and spreads to secondary cells within the same host, or to a new host, is not known. Here, we demonstrate that a subpopulation of Salmonella hyperreplicating in the cytosol of epithelial cells serves as a reservoir for dissemination. These bacteria are transcriptionally distinct from intravacuolar Salmonella. They are induced for the invasion-associated type III secretion system and possess flagella; hence, they are primed for invasion. Epithelial cells laden with these cytosolic bacteria are extruded out of the monolayer, releasing invasion-primed and -competent Salmonella into the lumen. This extrusion mechanism is morphologically similar to the process of cell shedding required for turnover of the intestinal epithelium. In contrast to the homeostatic mechanism, however, bacterial-induced extrusion is accompanied by an inflammatory cell death characterized by caspase-1 activation and the apical release of IL-18, an important cytokine regulator of gut inflammation. Although epithelial extrusion is obviously beneficial to Salmonella for completion of its life cycle, it also provides a mechanistic explanation for the mucosal inflammation that is triggered during Salmonella infection of the gastrointestinal and biliary tracts.
肠道沙门氏菌是一种细胞内细菌病原体，它在肠道和胆囊的上皮细胞的膜结合空泡中存活和增殖。尽管这对疾病的发生至关重要，但沙门氏菌如何从其细胞内栖息地中逃脱并传播到同一宿主的次级细胞，或传播到新宿主，目前尚不清楚。在这里，我们证明了在肠上皮细胞的细胞质中高度复制的沙门氏菌的亚群是传播的储备库。这些细菌在转录上与腔内沙门氏菌不同。它们被诱导与入侵相关的 III 型分泌系统，并具有鞭毛;因此，它们已准备好进行入侵。富含这些细胞质细菌的上皮细胞被挤出单层，将入侵引发和有能力的沙门氏菌释放到腔中。这种挤出机制在形态上类似于肠上皮细胞更新所需的细胞脱落过程。然而，与体内平衡机制不同的是，细菌诱导的挤出伴随着细胞凋亡的炎症性细胞死亡，其特征是半胱天冬酶-1 的激活和白细胞介素-18 的顶端释放，白细胞介素-18 是肠道炎症的重要细胞因子调节剂。尽管上皮细胞的挤出显然有利于沙门氏菌完成其生命周期，但它也为胃肠道和胆道沙门氏菌感染引发的粘膜炎症提供了一种机制解释。
