DOP49 Quantitative proteomics analysis of macrophages from Crohn’s disease patients and infected with adherent-invasive
C. Douadi1, E. Vazeille1, C. Chambon2, M. Hébraud3, M. Dodel4, B. Pereira4, D. Coban4, A. Buisson4, N. Barnich1
1Clermont-Auvergne University, M2iSH Laboratory, Clermont-Ferrand, France, 2INRA, Plateforme d’Exploration du Métabolisme- Composante Protéomique PFEMcp, Saint-Genès-Champanelle, France, 3INRA, UMR Microbiologie Environnement Digestif Santé MEDiS, Saint-Genès-Champanelle, France, 4CHU, Gastro-entérologie, Clermont-Ferrand, France
Crohn’s disease (CD) is a disabling inflammatory bowel disease. Currently, the available treatments only alleviate the symptoms. The anti-TNFα represent the most efficient therapeutic class, but its mechanisms are poorly known. Experimental data have highlighted the role of intestinal macrophages in the pathogenesis of CD. These macrophages present a defect in the control of CD-associated adherent-invasive
Peripheral blood monocyte-derived macrophages (MDM) were obtained from 44 CD patients including 22 with and 22 without anti-TNFα treatment, 22 UC patients and 22 healthy subjects. MDM was infected or not with AIEC LF82 reference strain. The numbers of intracellular bacteria were determined at 1h and 6h post-infection, using gentamicin protection assay. The ‘bottom-up’ proteomic analysis of macrophages after 6h of AIEC LF82 infection or not, was assessed by a mass spectrometer, using the
AIEC survival was reduced within MDM from CD patients with anti-TNFα treatment compared with those from CD without TNFα treatment (
Our study highlighted that the anti-TNFα treatment limits bacteria replication and acts on macrophages function. For the first time, global proteomic analysis suggests that CD macrophages-AIEC interaction could be orchestrated by ITGB3, GPx-1, PRDX3 and FUCA-1. These proteins could represent potential therapeutic targets in CD patients that need to be further investigated.