Enteric glia protect against Shigella flexneri invasion in intestinal epithelial cells: a role for S-nitrosoglutathione

Flamant, Mathurin; Aubert, P.; Rolli–Derkinderen, Malvyne; Bourreille, Arnaud; Neunlist, Margarida Ribeiro; Mahé, Maxime M.; Meurette, G.; Marteyn, Benoît; Savidge, Tor; Galmiche, Jean Paul; Sansonetti, Philippe J.; Neunlist, Michel

doi:10.1136/gut.2010.229237

Cited by 85 publications

(81 citation statements)

References 44 publications

(52 reference statements)

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“…Recently, human tissue preparations consisting of separated serosa and circular muscle have been used to culture the mucosal and submucosal fragments. From this model, and given that the enteric nervous system is a potent modulator of intestinal epithelial barrier functions (30), knowledge of the role of enteric neurons in intestinal Shigella pathogenesis is beginning to emerge (655,871,872). Moreover, two coculture models, consisting of human submucosa containing the submucosal neuronal network and human fully differentiated, mucus-secreting HT29-Cl.16E or enterocyte-like Caco-2 monolayers, have been described.…”

Section: Discussionmentioning

confidence: 99%

“…S. flexneri serotype 2a adhering apically onto fully differentiated T84 cells secretes bacterial products that have the ability to alter the TJs by inducing the delocalization of ZO-1, occludin, and claudin-1 from membrane lipid rafts and the dephosphorylation of occludin (654). In fully differentiated Caco-2 cells cocultured with enteric glial cells, which function as important regulators of intestinal epithelial barrier functions, and in ex vivo cultured human colonic mucosa, Flamant et al (655) observed a reduced deleterious effect of S. flexneri on the TJs, indicating that the enteric glial cells have a protective effect against the lesions at the intestinal barrier caused by an invasive pathogen.…”

Section: Structural and Functional Injuries At The Junctional Domainmentioning

confidence: 99%

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Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines

Moal

Servin

2013

Microbiol Mol Biol Rev

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SUMMARY Hosts are protected from attack by potentially harmful enteric microorganisms, viruses, and parasites by the polarized fully differentiated epithelial cells that make up the epithelium, providing a physical and functional barrier. Enterovirulent bacteria interact with the epithelial polarized cells lining the intestinal barrier, and some invade the cells. A better understanding of the cross talk between enterovirulent bacteria and the polarized intestinal cells has resulted in the identification of essential enterovirulent bacterial structures and virulence gene products playing pivotal roles in pathogenesis. Cultured animal cell lines and cultured human nonintestinal, undifferentiated epithelial cells have been extensively used for understanding the mechanisms by which some human enterovirulent bacteria induce intestinal disorders. Human colon carcinoma cell lines which are able to express in culture the functional and structural characteristics of mature enterocytes and goblet cells have been established, mimicking structurally and functionally an intestinal epithelial barrier. Moreover, Caco-2-derived M-like cells have been established, mimicking the bacterial capture property of M cells of Peyer's patches. This review intends to analyze the cellular and molecular mechanisms of pathogenesis of human enterovirulent bacteria observed in infected cultured human colon carcinoma enterocyte-like HT-29 subpopulations, enterocyte-like Caco-2 and clone cells, the colonic T84 cell line, HT-29 mucus-secreting cell subpopulations, and Caco-2-derived M-like cells, including cell association, cell entry, intracellular lifestyle, structural lesions at the brush border, functional lesions in enterocytes and goblet cells, functional and structural lesions at the junctional domain, and host cellular defense responses.

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Section: Discussionmentioning

confidence: 99%

Section: Structural and Functional Injuries At The Junctional Domainmentioning

confidence: 99%

Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines

Moal

Servin

2013

Microbiol Mol Biol Rev

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“…Indeed, it has been suggested that similar to the enhancing effects of astrocytes on the blood-brain barrier (69), these mucosal EGCS (mEGCs) play a critical role in maintaining the barrier function of the intestinal epithelium, an effect that is likely to be mediated by s-nitrosoglutathione (80,81). Although further work is necessary to characterize in detail the mechanisms by which mEGCs support the barrier activity of the intestinal epithelium (82), these findings already raise interesting questions relating to the development and homeostasis of these cells.…”

Section: Microbiota Influence On Ens Developmentmentioning

confidence: 99%

Emerging roles of gut microbiota and the immune system in the development of the enteric nervous system

Kabouridis¹,

Pachnis²

2015

J. Clin. Invest.

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“…Since UC is characterized by abnormal mucosal NO production and associated proinflammatory cytokines, it is tempting to speculate that these mediators might affect enteric neuron function and thus gut physiology. Furthermore, data obtained with an ex vivo human model of infectious disease (i.e., Shigella flexneri) have shown that neuronal cell death was associated with EGC loss (15,18). Notably, S. flexneri-induced neurodegeneration was mediated via N-methyl-D-aspartate receptors, suggesting a reduced glutamate reuptake secondary to EGC damage and loss.…”

Section: Egc Abnormalities In the Clinical Settingmentioning

confidence: 99%

Enteric glia and neuroprotection: basic and clinical aspects

Giorgio

Giancola

Boschetti

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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The enteric nervous system (ENS), a major regulatory system for gastrointestinal function, is composed of neurons and enteric glial cells (EGCs). Enteric glia have long been thought to provide only structural support to neurons. However, recent evidence indicates enteric glia-neuron cross talk significantly contributes to neuronal maintenance, survival, and function. Thus damage to EGCs may trigger neurodegenerative processes thought to play a role in gastrointestinal dysfunctions and symptoms. The purpose of this review is to provide an update on EGCs, particularly focusing on their possible neuroprotective features and the resultant enteric neuron abnormalities subsequent to EGC damage. These neuroprotective mechanisms may have pathogenetic relevance in a variety of functional and inflammatory gut diseases. Basic and clinical (translational) studies support a neuroprotective role mediated by EGCs. Different models have been developed to test whether selective EGC damage/ablation has an impact on gut functions and the ENS. Preclinical data indicated that selective EGC alterations were associated with changes in gut physiology related to enteric neuron abnormalities. In humans, a substantial loss of EGCs was described in patients with various functional and/or inflammatory gastrointestinal diseases. However, whether EGC changes precede or follow neuronal degeneration and loss and how this damage occurs is not defined. Additional studies on EGC neuroprotective capacity are expected to improve knowledge of gut diseases and pave the way for targeted therapeutic strategies of underlying neuropathies. enteric glia; enteric neurons; enteric neuropathy; neuroprotection; neurodegeneration DIGESTION, I.E., THE BREAKDOWN and mixing of food with secretions, nutrient digestion and absorption, propulsion of the contents throughout the gut, and, finally, the expulsion of undigested material, requires a vast repertoire of highly integrated regulatory mechanisms. These are finely tuned by a variety of cell types, including endocrine cells [distributed throughout the gastrointestinal (GI) mucosa], smooth muscle cells (final effectors of contractility and/or relaxation), interstitial cells of Cajal (ICC) (pacemakers of gut motility and regulators of neuromuscular transmission), and neurons of both intrinsic (enteric) and extrinsic (sympathetic and parasympathetic) origin (50). The neural network of the digestive system, including the enteric nervous system (ENS), exerts a prominent regulatory role. From a structural standpoint, the ENS contains about 100 to 500 million neuronal cell bodies organized in two major ganglionated plexuses (i.e., myenteric and submucosal), neural processes connecting the ganglia among them, and nerve fibers targeting many different effector cells. In addition to neurons, enteric glial cells (EGCs) were recently identified as key players in the ENS. EGCs, which form the largest cell population of the ENS, have long been thought to exert a mere mechanical property by supporting neurons (hence the ancient...

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Enteric glia protect against Shigella flexneri invasion in intestinal epithelial cells: a role for S-nitrosoglutathione

Abstract: These results highlight a major protective function of EGCs and GSNO in the IEB against S flexneri attack. Consequently, this study lays the scientific basis for using GSNO to reduce barrier susceptibility to infectious or inflammatory challenge.

Cited by 85 publications

References 44 publications

Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines

Pathogenesis of Human Enterovirulent Bacteria: Lessons from Cultured, Fully Differentiated Human Colon Cancer Cell Lines

Emerging roles of gut microbiota and the immune system in the development of the enteric nervous system

Enteric glia and neuroprotection: basic and clinical aspects

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