Cholera Toxin Disrupts Barrier Function by Inhibiting Exocyst-Mediated Trafficking of Host Proteins to Intestinal Cell Junctions

Guichard, Annabel; Cruz-Moreno, Beatriz; Aguilar, Berenice; Sorge, Nina M. van; Kuang, Jennifer; Kurkciyan, Adrianne; Wang, Zhipeng; Hang, Saiyu; Chambrun, Guillaume P. Pineton de; McCole, Declan F.; Watnick, Paula I.; Nizet, Victor; Bier, Ethan

doi:10.1016/j.chom.2013.09.003

Cited by 19 publications

(29 citation statements)

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“…This was in line with the recent study that CT disrupted the barrier function of Caco-2 intestinal ECs. 43 Besides, in PPs, CT combined with H9N2 WIV strongly enhanced the potential abilities of DC recruitment, consistent with previous report. 44 Expression of CCL20 in response to CpGs combined with H9N2 whole inactivated influenza virus (WIV) for DC recruitment.…”

Section: Discussionsupporting

confidence: 89%

CpG DNA assists the whole inactivated H9N2 influenza virus in crossing the intestinal epithelial barriers via transepithelial uptake of dendritic cell dendrites

et al. 2015

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Intestinal mucosa remains a pivotal barrier for the oral vaccine absorption of H9N2 whole inactivated influenza virus (WIV). However, CpG DNA, as an adjuvant, can effectively improve relevant mucosal and systemic immunity. The downstream mechanism is well confirmed, yet the evidence of CpG DNA assisting H9N2 WIV in transepithelial delivery is lacking. Here, we reported both in vitro and in vivo that CpG DNA combined with H9N2 WIV was capable of recruiting additional dendritic cells (DCs) to the intestinal epithelial cells (ECs) to form transepithelial dendrites (TEDs) for luminal viral uptake. Both CD103(+) and CD103(-) DCs participated in this process. The engagement of the chemokine CCL20 from the apical ECs and the DCs drove DC recruitment and TED formation. Virus-loaded CD103(+) but not CD103(-) DCs also quickly migrated into mesenteric lymph nodes within 2 h. Moreover, the mechanism of CpG DNA was independent of epithelial transcytosis and disruption of the epithelial barriers. Finally, the subsequent phenotypic and functional maturation of DCs was also enhanced. Our findings indicated that CpG DNA improved the delivery of H9N2 WIV via TEDs of intestinal DCs, and this may be an important mechanism for downstream effective antigen-specific immune responses.

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Section: Discussionsupporting

confidence: 89%

CpG DNA assists the whole inactivated H9N2 influenza virus in crossing the intestinal epithelial barriers via transepithelial uptake of dendritic cell dendrites

et al. 2015

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“…In healthy endothelial or epithelial cells, the GTPase Rab11 interacts with the exocyst component Sec15 on recycling endosome (RE) compartments to mediate the exocytic delivery of cadherins and the Notch ligand Delta proteins to cell–cell junctions. The anthrax toxin A subunit oedema factor (EF) and the cholera toxin A subunit CtxA each interfere with delivery of cadherins and Notch by inhibiting the accumulation of Rab11 on exocytic vesicles (Guichard et al, ; Guichard et al, ; Guichard et al, ). This inhibition is mediated by cAMP‐dependent activation of EPAC and the EPAC effector Rap1.…”

Section: Exocytosis and Microbial Pathogenesismentioning

confidence: 99%

“…Two different bacterial pathogens, Bacillus anthracis and Vibrio cholerae , produce toxins that disrupt Rab11‐mediated exocytic trafficking of cadherins to cell–cell junctions (Guichard et al, ; Guichard et al, ; Guichard et al, ; Figure c). By doing so, these toxins perturb the barrier functions of tissues, leading to fluid leakage that contributes to oedema during late stages of B. athracis infection or watery diarrhoea in cases of cholera.…”

Section: Exocytosis and Microbial Pathogenesismentioning

confidence: 99%

Interaction of microbial pathogens with host exocytic pathways

Ireton

Ngo

Bhalla

2018

Cellular Microbiology

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Many microbial pathogens co-opt or perturb host membrane trafficking pathways. This review covers recent examples in which microbes interact with host exocytosis, the fusion of intracellular vesicles with the plasma membrane. The bacterial pathogens Listeria monocytogenes and Staphylococcus aureus subvert recycling endosomal pathways of exocytosis in order to induce their entry into human cells. By contrast, entry of the protozoan pathogen Trypanosoma cruzi or the virus adenovirus into host cells involves exploitation of lysosomal exocytosis. Toxins produced by Bacillus anthracis or Vibrio cholerae interfere with exocytosis pathways mediated by the GTPase Rab11 and the exocyst complex. By doing so, anthrax or cholera toxins impair recycling of cadherins to cell-cell junctions and disrupt the barrier properties of endothelial cells or intestinal epithelial cells, respectively. Uropathogenic Escherichia coli (UPEC) is expelled from bladder epithelial cells through two different exocytic routes that involve sensing of bacteria in vacuoles by host Toll-like receptor 4 (TLR4) or monitoring of the pH of lysosomes harbouring UPEC. The TLR4 pathway is mediated by multiple Rab GTPases and the exocyst, whereas the other pathway involves exocytosis of lysosomes. Expulsion of UPEC through these pathways is thought to benefit the host.

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“…In addition, the electroneutral absorption of NaCl from the intestinal lumen is inhibited by the increase in cAMP concentration [166]. Moreover, the transport of necessary proteins to the tight junction is inhibited by cAMP, increasing the junctions' permeability for Na + [167]. These are only some of the more obvious effects of cAMP production that increase the toxic effect, and many more have been reported.…”

Section: Action Of the A1 Fragment In The Cytosolmentioning

confidence: 97%

Vibrio cholerae and Escherichia coli heat-labile enterotoxins and beyond

Heggelund

Bjørnestad

Krengel

2015

The Comprehensive Sourcebook of Bacterial Protein Toxins

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Cholera Toxin Disrupts Barrier Function by Inhibiting Exocyst-Mediated Trafficking of Host Proteins to Intestinal Cell Junctions

Abstract: In the print version of the above article, the name of author Beatriz Cruz-Moreno was printed incorrectly due to a production error. This has now been corrected online, and we apologize for any inconvenience this has caused.

Cited by 19 publications

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CpG DNA assists the whole inactivated H9N2 influenza virus in crossing the intestinal epithelial barriers via transepithelial uptake of dendritic cell dendrites

CpG DNA assists the whole inactivated H9N2 influenza virus in crossing the intestinal epithelial barriers via transepithelial uptake of dendritic cell dendrites

Interaction of microbial pathogens with host exocytic pathways

Vibrio cholerae and Escherichia coli heat-labile enterotoxins and beyond

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