Monocyte-derived dendritic cells from Crohn patients show differential NOD2/CARD15-dependent immune responses to bacteria

Valentina Salucci, Monica Rimoldi, Chiara Penati, Gianluca M. Sampietro, Marjan Maria Van Duist, Gianluca Matteoli, Simone Saibeni, Maurizio Vecchi, Sandro Ardizzone, Gabriele Bianchi Porro, Maria Rescigno

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)812-818
Number of pages7
JournalInflammatory Bowel Diseases
Volume14
Issue number6
DOIs
Publication statusPublished - Jun 2008

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Keywords

  • Bacteria
  • Cell activation
  • Crohn's disease
  • Dendritic cells
  • Inflammation

ASJC Scopus subject areas

  • Gastroenterology

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