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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, Monocyte-derived dendritic cells from Crohn patients show differential NOD2/CARD15-dependent immune responses to bacteria, Inflammatory Bowel Diseases, Volume 14, Issue 6, 1 June 2008, Pages 812–818, https://doi.org/10.1002/ibd.20390
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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.
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.
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.
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.
