6533b7dafe1ef96bd126f652
RESEARCH PRODUCT
Role of meprins to protect ileal mucosa of Crohn's disease patients from colonization by adherent-invasive E. coli
Aurélie GardarinAurélie GardarinEmilie VazeilleEmilie VazeilleArlette Darfeuille-michaudArlette Darfeuille-michaudSylvia L.f. PenderDaniel LottazChristoph Becker-paulyStefan MüllerChristine JakobChristophe ChambonMarie-agnès BringerMarie-agnès Bringersubject
MaleBacterial Diseasesmedicine.medical_treatmentACTIVATION MECHANISMBiochemistryBacterial AdhesionPilusMice0302 clinical medicineCrohn DiseaseIntestinal mucosaMolecular Cell BiologyGastrointestinal InfectionsIntestinal MucosaAged 80 and over0303 health sciencesMultidisciplinaryQRMetalloendopeptidasesMiddle AgedEnzymesBacterial Pathogens3. Good healthHost-Pathogen InteractionInfectious DiseasesCytokineESCHERICHIA-COLI030220 oncology & carcinogenesisAlimentation et NutritionMedicineFemaleINFLAMMATORY-BOWEL-DISEASE;INTESTINAL EPITHELIAL-CELLS;URINARY-TRACT-INFECTIONS;ESCHERICHIA-COLI;ALPHA-SUBUNIT;STRAIN LF82;METALLOPROTEASE MEPRIN;ACTIVATION MECHANISM;BETA-SUBUNIT;TYPE-1 PILICellular Typesmedicine.symptomBacterial outer membraneALPHA-SUBUNITResearch ArticleAdultProteasesScienceMédecine humaine et pathologieInflammationGastroenterology and HepatologyBiologyMETALLOPROTEASE MEPRINMicrobiologyMicrobiologyURINARY-TRACT-INFECTIONS03 medical and health sciencesTYPE-1 PILIEscherichia colimedicineAnimalsHumansFood and NutritionSecretionInterleukin 8BETA-SUBUNITBiologyAged030304 developmental biologySTRAIN LF82Interleukin-8Inflammatory Bowel DiseaseEpithelial Cellsdigestive system diseasesMice Inbred C57BLHuman health and pathologyINTESTINAL EPITHELIAL-CELLS[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition[SDV.MHEP]Life Sciences [q-bio]/Human health and pathologyINFLAMMATORY-BOWEL-DISEASEdescription
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 beta. 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 alpha and meprin beta. Dose-dependent proteolytic degradation of type 1 pili was observed in the presence of active meprins, but not with heatinactivated 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2011-06-16 |