Tight Junctions As a Key for Pathogens Invasion in Intestinal Epithelial Cells

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Apr 3

PMID 33801524

Citations 74

Authors

Tracy Paradis

Herve Begue

Louise Basmaciyan

Frederic Dalle

Fabienne Bon

Affiliations

Soon will be listed here.

Abstract

Tight junctions play a major role in maintaining the integrity and impermeability of the intestinal barrier. As such, they act as an ideal target for pathogens to promote their translocation through the intestinal mucosa and invade their host. Different strategies are used by pathogens, aimed at directly destabilizing the junctional network or modulating the different signaling pathways involved in the modulation of these junctions. After a brief presentation of the organization and modulation of tight junctions, we provide the state of the art of the molecular mechanisms leading to permeability breakdown of the gut barrier as a consequence of tight junctions' attack by pathogens, including bacteria, viruses, fungi, and parasites.

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References

Awad W, Hess C, Hess M . Enteric Pathogens and Their Toxin-Induced Disruption of the Intestinal Barrier through Alteration of Tight Junctions in Chickens. Toxins (Basel). 2017; 9(2). PMC: 5331439. DOI: 10.3390/toxins9020060. View

Wang W, Uzzau S, Goldblum S, Fasano A . Human zonulin, a potential modulator of intestinal tight junctions. J Cell Sci. 2000; 113 Pt 24:4435-40. DOI: 10.1242/jcs.113.24.4435. View

Helmy Y, Kassem I, Kumar A, Rajashekara G . Evaluation of the Impact of the Probiotic Nissle 1917 on 's Invasion and Intracellular Survival in Human Colonic Cells. Front Microbiol. 2017; 8:1588. PMC: 5572226. DOI: 10.3389/fmicb.2017.01588. View

Sarkar P, Saha T, Sheikh I, Chakraborty S, Aoun J, Chakrabarti M . Zinc ameliorates intestinal barrier dysfunctions in shigellosis by reinstating claudin-2 and -4 on the membranes. Am J Physiol Gastrointest Liver Physiol. 2018; 316(2):G229-G246. PMC: 6397338. DOI: 10.1152/ajpgi.00092.2018. View

Backert S, Boehm M, Wessler S, Tegtmeyer N . Transmigration route of Campylobacter jejuni across polarized intestinal epithelial cells: paracellular, transcellular or both?. Cell Commun Signal. 2013; 11:72. PMC: 3850506. DOI: 10.1186/1478-811X-11-72. View

Capaldo C, Nusrat A . Cytokine regulation of tight junctions. Biochim Biophys Acta. 2008; 1788(4):864-71. PMC: 2699410. DOI: 10.1016/j.bbamem.2008.08.027. View

Boehm M, Simson D, Escher U, Schmidt A, Bereswill S, Tegtmeyer N . Function of Serine Protease HtrA in the Lifecycle of the Foodborne Pathogen . Eur J Microbiol Immunol (Bp). 2018; 8(3):70-77. PMC: 6186014. DOI: 10.1556/1886.2018.00011. View

Yan H, Ajuwon K . Butyrate modifies intestinal barrier function in IPEC-J2 cells through a selective upregulation of tight junction proteins and activation of the Akt signaling pathway. PLoS One. 2017; 12(6):e0179586. PMC: 5487041. DOI: 10.1371/journal.pone.0179586. View

Peng M, Liu J, Liang Z . Probiotic Bacillus subtilis CW14 reduces disruption of the epithelial barrier and toxicity of ochratoxin A to Caco-2 cells. Food Chem Toxicol. 2019; 126:25-33. DOI: 10.1016/j.fct.2019.02.009. View

10.

Lapointe T, OConnor P, Jones N, Menard D, Buret A . Interleukin-1 receptor phosphorylation activates Rho kinase to disrupt human gastric tight junctional claudin-4 during Helicobacter pylori infection. Cell Microbiol. 2010; 12(5):692-703. DOI: 10.1111/j.1462-5822.2010.01429.x. View

11.

Morampudi V, Graef F, Stahl M, Dalwadi U, Conlin V, Huang T . Tricellular Tight Junction Protein Tricellulin Is Targeted by the Enteropathogenic Escherichia coli Effector EspG1, Leading to Epithelial Barrier Disruption. Infect Immun. 2016; 85(1). PMC: 5203647. DOI: 10.1128/IAI.00700-16. View

12.

Nakashima R, Kamata Y, Nishikawa Y . Effects of Escherichia coli heat-stable enterotoxin and guanylin on the barrier integrity of intestinal epithelial T84 cells. Vet Immunol Immunopathol. 2012; 152(1-2):78-81. DOI: 10.1016/j.vetimm.2012.09.026. View

13.

Maia-Brigagao C, Morgado-Diaz J, De Souza W . Giardia disrupts the arrangement of tight, adherens and desmosomal junction proteins of intestinal cells. Parasitol Int. 2011; 61(2):280-7. DOI: 10.1016/j.parint.2011.11.002. View

14.

Cerutti C, Ridley A . Endothelial cell-cell adhesion and signaling. Exp Cell Res. 2017; 358(1):31-38. PMC: 5700119. DOI: 10.1016/j.yexcr.2017.06.003. View

15.

Fasano A, Fiorentini C, Donelli G, Uzzau S, Kaper J, Margaretten K . Zonula occludens toxin modulates tight junctions through protein kinase C-dependent actin reorganization, in vitro. J Clin Invest. 1995; 96(2):710-20. PMC: 185254. DOI: 10.1172/JCI118114. View

16.

Steed E, Balda M, Matter K . Dynamics and functions of tight junctions. Trends Cell Biol. 2010; 20(3):142-9. DOI: 10.1016/j.tcb.2009.12.002. View

17.

Philpott D, McKay D, Mak W, Perdue M, Sherman P . Signal transduction pathways involved in enterohemorrhagic Escherichia coli-induced alterations in T84 epithelial permeability. Infect Immun. 1998; 66(4):1680-7. PMC: 108105. DOI: 10.1128/IAI.66.4.1680-1687.1998. View

18.

Olivier S, Leclerc J, Grenier A, Foretz M, Tamburini J, Viollet B . AMPK Activation Promotes Tight Junction Assembly in Intestinal Epithelial Caco-2 Cells. Int J Mol Sci. 2019; 20(20). PMC: 6829419. DOI: 10.3390/ijms20205171. View

19.

Campbell H, Maiers J, DeMali K . Interplay between tight junctions & adherens junctions. Exp Cell Res. 2017; 358(1):39-44. PMC: 5544570. DOI: 10.1016/j.yexcr.2017.03.061. View

20.

Alvarez C, Gimenez R, Canas M, Vera R, Diaz-Garrido N, Badia J . Extracellular vesicles and soluble factors secreted by Escherichia coli Nissle 1917 and ECOR63 protect against enteropathogenic E. coli-induced intestinal epithelial barrier dysfunction. BMC Microbiol. 2019; 19(1):166. PMC: 6637528. DOI: 10.1186/s12866-019-1534-3. View