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Role of meprins to protect ileal mucosa of Crohn's disease patients from colonization by adherent-invasive E. coli

Record type: Article

Ileal lesions in Crohn's disease (CD) patients are colonized by pathogenic adherent-invasive Escherichia coli (AIEC) able to adhere to and invade intestinal epithelial cells (IEC), and to survive within macrophages. The interaction of AIEC with IEC depends on bacterial factors mainly type 1 pili, flagella, and outer membrane proteins. In humans, proteases can act as host defence mechanisms to counteract bacterial colonization. The protease meprin, composed of multimeric complexes of the two subunits alpha and beta, is abundantly expressed in IECs. Decreased levels of this protease correlate with the severity of the inflammation in patients with inflammatory bowel disease. The aim of the present study was to analyze the ability of meprin to modulate the interaction of AIEC with IECs. In patients with ileal CD we observed decreased levels of meprins, in particular that of meprin ?. Dose-dependent inhibition of the abilities of AIEC strain LF82 to adhere to and invade intestinal epithelial T84 cells was observed when bacteria were pre-treated with both exogenous meprin ? and meprin ?. Dose-dependent proteolytic degradation of type 1 pili was observed in the presence of active meprins, but not with heat-inactivated meprins, and pretreatment of AIEC bacteria with meprins impaired their ability to bind mannosylated host receptors and led to decreased secretion of the pro-inflammatory cytokine IL-8 by infected T84 cells. Thus, decreased levels of protective meprins as observed in CD patients may contribute to increased AIEC colonization.

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Citation

Vazeille, Emilie, Bringer, Marie-Agnès, Gardarin, Aurélie, Chambon, Christophe, Becker-Pauly, Christoph, Pender, Sylvia L.F., Jakob, Christine, Müller, Stefan, Lottaz, Daniel and Darfeuille-Michaud, Arlette (2011) Role of meprins to protect ileal mucosa of Crohn's disease patients from colonization by adherent-invasive E. coli PLoS ONE, 6, (6), e21199. (doi:10.1371/journal.pone.0021199). (PMID:10862792).

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Published date: 16 June 2011
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 195601
URI: http://eprints.soton.ac.uk/id/eprint/195601
ISSN: 1932-6203
PURE UUID: eed06dbf-70db-4905-b48b-47d2dd9faffc
ORCID for Sylvia L.F. Pender: ORCID iD orcid.org/0000-0001-6332-0333

Catalogue record

Date deposited: 23 Aug 2011 14:06
Last modified: 18 Jul 2017 11:24

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Contributors

Author: Emilie Vazeille
Author: Marie-Agnès Bringer
Author: Aurélie Gardarin
Author: Christophe Chambon
Author: Christoph Becker-Pauly
Author: Christine Jakob
Author: Stefan Müller
Author: Daniel Lottaz
Author: Arlette Darfeuille-Michaud

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