Monocyte-derived dendritic cells from Crohn patients show differential NOD2/CARD15-dependent immune responses to bacteria
Version of Record online: 31 JAN 2008
Copyright © 2008 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 14, Issue 6, pages 812–818, June 2008
How to Cite
Salucci, V., Rimoldi, M., Penati, C., Sampietro, G. M., van Duist, M. M., Matteoli, G., Saibeni, S., Vecchi, M., Ardizzone, S., Porro, G. B. and Rescigno, M. (2008), Monocyte-derived dendritic cells from Crohn patients show differential NOD2/CARD15-dependent immune responses to bacteria. Inflamm Bowel Dis, 14: 812–818. doi: 10.1002/ibd.20390
- Issue online: 5 MAY 2008
- Version of Record online: 31 JAN 2008
- Manuscript Accepted: 14 DEC 2007
- Manuscript Received: 2 MAR 2007
- Crohn's and Colitis Foundation of America
- Italian Ministry of Health (Ricerca finalizzata)
- Italian Association for Cancer Research
- MWR grant. Grant Number: 2004064901
- dendritic cells;
- cell activation;
- Crohn's disease
Background: Three common mutations in the NOD2/CARD15 gene are strongly associated with Crohn's disease (CD). NOD2 is an intracellular receptor of muramyl dipeptide (MDP), a component of peptidoglycan present in the cell wall of Gram-positive (G+) and Gram-negative (G−) bacteria.
Methods: We generated monocyte-derived dendritic cells (MoDCs) from CD patients mutated or not for CARD15 (n = 53) or from healthy donors (n = 12) and analyzed their activation in response to live Salmonella typhimurium as a model of pathogenic G− bacteria.
Results: MoDCs carrying the L1007fs mutation, although phenotypically activated by bacteria, produced a significantly reduced amount of tested cytokines. MoDCs carrying R702W or compound G908R/R702W NOD2 mutations displayed an increased basal level of IL-8 release. After a bacterial encounter, these cells were phenotypically activated and produced levels of cytokines similar to healthy controls. Interestingly, although L1007fs/WT mutations conferred reduced production of cytokines, including IL-12, these cells were perfectly capable of inducing T-cell polarization toward the Th1 phenotype.
Conclusions: NOD2 mutations affect the basal characteristics of MoDCs and their response to G− bacteria differently. MoDCs could be involved in CD onset because they have defects in releasing inflammatory cytokines and in polarizing T-cell responses.
(Inflamm Bowel Dis 2008)