Sansonetti P J
Unité de Pathogénie Microbienne Moléculaire, INSERM U 389, Institut Pasteur, Paris, France.
Folia Microbiol (Praha). 1998;43(3):239-46. doi: 10.1007/BF02818608.
The pathogenesis of bacillary dysentery can be studied at different levels of integration of the cellular components that constitute the colonic mucosal barrier. We considered the interaction of Shigella flexneri in three experimental systems that provide complementary information and a scheme of events occurring in human colorectal mucosa as Shigella invasion proceeds. Interaction of S. flexneri with individual epithelial cells shows a series of events in which the bacterium, upon contact with the cell surface, releases a set of Ipa proteins (i.e. invasins) through a specialized, activable, type-III secretory apparatus (i.e. Mxi/Spa). Via a complex signaling process, these invasins cause major rearrangements of the subcortical cytoskeletal network which allow bacterial entry by a macropinocytotic event. Then the bacterium lyses its phagocytotic vacuole and initiates intracytoplasmic movement, due to polar assembly of actin filaments caused by a bacterial surface protein, IcsA. This allows very efficient colonization of the host cell cytoplasm and passage to adjacent cells via protrusions which are engulfed by a cadherin-dependent process. However, when invasive Shigella are deposited on the apical side of polarized monolayers of human colonic cells, they appear unable to invade, indicating that bacteria need to reach the subepithelial area to invade the epithelium. In this system, it has been shown that transepithelial signaling caused by apical bacteria induces adherence and transmigration of basal polymorphonuclears (PMN), thus disrupting the monolayer permeability and facilitating bacterial invasion. LPS accounts for a large part of this transepithelial signalization to PMN. Such a process could account for invasion in intestinal crypts. Finally, models of infection, such as the rabbit ligated intestinal loop show that initial bacterial entry occurs essentially via M cells of the follicular associated epithelium. It then causes apoptosis of macrophages located in the follicular dome, inducing release of IL-1 beta which, in turn, initiates inflammation, leading to destabilization of the epithelial structures as modeled above. These data can now be used to understand the mechanisms of mucosal protection against bacillary dysentery.
可在构成结肠黏膜屏障的细胞成分的不同整合水平上研究细菌性痢疾的发病机制。我们在三个实验系统中研究了福氏志贺菌的相互作用，这些系统提供了互补信息以及随着志贺菌侵袭过程在人结肠黏膜中发生的一系列事件。福氏志贺菌与单个上皮细胞的相互作用显示出一系列事件，在此过程中，细菌在与细胞表面接触后，通过一种特殊的、可激活的III型分泌装置（即Mxi/Spa）释放一组Ipa蛋白（即侵袭素）。通过复杂的信号传导过程，这些侵袭素会引起皮质下细胞骨架网络的重大重排，从而通过巨吞饮事件使细菌进入。然后，细菌裂解其吞噬泡并开始胞质内移动，这是由细菌表面蛋白IcsA引起的肌动蛋白丝的极性组装所致。这使得宿主细胞质能够非常有效地定殖，并通过突起传递到相邻细胞，这些突起通过钙黏蛋白依赖性过程被吞噬。然而，当侵袭性志贺菌沉积在人结肠细胞极化单层的顶端时，它们似乎无法侵袭，这表明细菌需要到达上皮下区域才能侵袭上皮。在这个系统中，已经表明顶端细菌引起的跨上皮信号传导会诱导基底多形核白细胞（PMN）的黏附和迁移，从而破坏单层通透性并促进细菌侵袭。LPS在这种向PMN的跨上皮信号传导中占很大一部分。这样的过程可以解释在肠隐窝中的侵袭。最后，感染模型，如兔结扎肠袢，表明最初的细菌进入主要通过滤泡相关上皮的M细胞发生。然后它会导致位于滤泡穹顶的巨噬细胞凋亡，诱导IL-1β的释放，进而引发炎症，导致上皮结构如上述那样不稳定。现在这些数据可用于理解黏膜预防细菌性痢疾的机制。
