Phalipon Armelle, Sansonetti Philippe J
Unité de Pathogénie Microbienne Moléculaire, INSERM U786, Institut Pasteur 25, Rue du Dr Roux, Paris, France.
Immunol Cell Biol. 2007 Feb-Mar;85(2):119-29. doi: 10.1038/sj.icb7100025. Epub 2007 Jan 9.
Shigella, a Gram-negative invasive enteropathogenic bacterium, causes the rupture, invasion and inflammatory destruction of the human colonic epithelium. This complex and aggressive process accounts for the symptoms of bacillary dysentery. The so-called invasive phenotype of Shigella is linked to expression of a type III secretory system (TTSS) injecting effector proteins into the epithelial cell membrane and cytoplasm, thereby inducing local but massive changes in the cell cytoskeleton that lead to bacterial internalization into non-phagocytic intestinal epithelial cells. The invasive phenotype also accounts for the potent pro-inflammatory capacity of the microorganism. Recent evidence indicates that a large part of the mucosal inflammation is initiated by intracellular sensing of bacterial peptidoglycan by cytosolic leucine-rich receptors of the NOD family, particularly NOD1, in epithelial cells. This causes activation of the nuclear factor kappa B and c-JunNH(2)-terminal-kinase pathways, with interleukin-8 appearing as a major chemokine mediating the inflammatory burst that is dominated by massive infiltration of the mucosa by polymorphonuclear leukocytes. Not unexpectedly, this inflammatory response, which is likely to be very harmful for the invading microbe, is regulated by the bacterium itself. A group of proteins encoded by Shigella, which are injected into target cells by the TTSS, has been recently recognized as a family of potent regulators of the innate immune response. These enzymes target key cellular functions that are essential in triggering the inflammatory response, and more generally defense responses of the intestinal mucosa. This review focuses on the mechanisms employed by Shigella to manipulate the host innate response in order to escape early bacterial killing, thus ensuring establishment of its infectious process. The escape strategies, the possible direct effect of Shigella on B and T lymphocytes, their impact on the development of adaptive immunity, and how they may help explain the limited protection induced by natural infection are discussed.
志贺氏菌是一种革兰氏阴性侵袭性肠道致病菌，可导致人类结肠上皮细胞破裂、侵袭和炎症性破坏。这一复杂且具有侵袭性的过程导致了细菌性痢疾的症状。志贺氏菌所谓的侵袭表型与III型分泌系统（TTSS）的表达有关，该系统将效应蛋白注入上皮细胞膜和细胞质中，从而诱导细胞骨架发生局部但大规模的变化，导致细菌内化进入非吞噬性肠上皮细胞。这种侵袭表型也解释了该微生物强大的促炎能力。最近的证据表明，大部分黏膜炎症是由上皮细胞中NOD家族富含亮氨酸的胞质受体，特别是NOD1对细菌肽聚糖的细胞内感知引发的。这会激活核因子κB和c-Jun氨基末端激酶途径，白细胞介素-8作为主要趋化因子出现，介导由多形核白细胞大量浸润黏膜所主导的炎症爆发。不出所料，这种可能对入侵微生物非常有害的炎症反应受到细菌自身的调节。志贺氏菌编码的一组蛋白质通过TTSS注入靶细胞，最近被认为是先天免疫反应的强效调节因子家族。这些酶靶向触发炎症反应以及更广泛地说肠道黏膜防御反应所必需的关键细胞功能。本综述重点关注志贺氏菌为操纵宿主先天反应以逃避早期细菌杀伤从而确保其感染过程得以建立所采用的机制。还讨论了逃逸策略、志贺氏菌对B和T淋巴细胞可能的直接影响、它们对适应性免疫发展的影响，以及它们如何有助于解释自然感染诱导的有限保护作用。
