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CARD15 variants determine a disturbed early response of monocytes to adherent-invasive Escherichia coli strain LF82 in Crohn's disease

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Abstract
Caspase activation and recruitment domain 15 (CARD15) and Toll-like receptor 4 (TLR4) are respectively intracellular and membrane-bound receptors for bacterial cell wall components [respectively muramyl dipeptide (MDP) and lipopolysaccharide ( LPS)]. Polymorphisms in CARD15 and TLR4 have been linked with Crohn's disease (CD). Adherent-invasive Escherichia coli (AIEC) strains with particular adhesion and invasion characteristics have been specifically associated with CD ileal mucosa. The aim of this study was to investigate the functional impact of these polymorphisms on monocytes in patients with CD, in response to MDP, LPS and AIEC strain LF82. Monocytes were isolated from 40 patients with CD using magnetic cell sorting, stimulated with LPS or MDP or infected with AIEC. IL-1 beta, IL-6, IL-8, IL-10, IL-12 and tumour necrosis factor alpha induction was assessed using quantitative real time-polymerase chain reaction, Cytometric Bead Array and ELISA. Bacterial intracellular survival and replication was assessed using a gentamicin protection assay. Results were linked with the presence of CARD15 and TLR4 polymorphisms. Monocytes of patients with CARD15 polymorphisms showed an early reduced cytokine response (IL-1 beta, IL-6 and IL-10) to infection with AIEC, which was restored after 20 h. A gene-dose effect was seen, comparing wild-types, heterozygotes and homozygotes. We found no differences in intracellular survival and replication of AIEC. Heterozygous carriage of TLR4 polymorphisms did not influence monocyte response. In conclusion, patients with CD carrying CARD15 polymorphisms show a disturbed early inflammatory monocyte response after infection with AIEC strain LF82. For the first time, a functional defect was detected in single heterozygous carriers. These findings reflect the potential role of a genetically altered host response to disease-related bacteria in the pathogenesis of CD.
Keywords
INFLAMMATORY-BOWEL-DISEASE, NF-KAPPA-B, ILEAL MUCOSA, ADAPTIVE IMMUNITY, NEOTERMINAL ILEUM, INTERFERON-GAMMA, NOD2, LIPOPOLYSACCHARIDE, MUTATIONS, EXPRESSION

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MLA
Peeters, Harald, Sara Bogaert, Debby Laukens, et al. “CARD15 Variants Determine a Disturbed Early Response of Monocytes to Adherent-invasive Escherichia Coli Strain LF82 in Crohn’s Disease.” INTERNATIONAL JOURNAL OF IMMUNOGENETICS 34.3 (2007): 181–191. Print.
APA
Peeters, Harald, Bogaert, S., Laukens, D., Rottiers, P., De Keyser, F., Darfeuille-Michaud, A., Glasser, A., et al. (2007). CARD15 variants determine a disturbed early response of monocytes to adherent-invasive Escherichia coli strain LF82 in Crohn’s disease. INTERNATIONAL JOURNAL OF IMMUNOGENETICS, 34(3), 181–191.
Chicago author-date
Peeters, Harald, Sara Bogaert, Debby Laukens, Pieter Rottiers, Filip De Keyser, A Darfeuille-Michaud, AL Glasser, Dirk Elewaut, and Martine De Vos. 2007. “CARD15 Variants Determine a Disturbed Early Response of Monocytes to Adherent-invasive Escherichia Coli Strain LF82 in Crohn’s Disease.” International Journal of Immunogenetics 34 (3): 181–191.
Chicago author-date (all authors)
Peeters, Harald, Sara Bogaert, Debby Laukens, Pieter Rottiers, Filip De Keyser, A Darfeuille-Michaud, AL Glasser, Dirk Elewaut, and Martine De Vos. 2007. “CARD15 Variants Determine a Disturbed Early Response of Monocytes to Adherent-invasive Escherichia Coli Strain LF82 in Crohn’s Disease.” International Journal of Immunogenetics 34 (3): 181–191.
Vancouver
1.
Peeters H, Bogaert S, Laukens D, Rottiers P, De Keyser F, Darfeuille-Michaud A, et al. CARD15 variants determine a disturbed early response of monocytes to adherent-invasive Escherichia coli strain LF82 in Crohn’s disease. INTERNATIONAL JOURNAL OF IMMUNOGENETICS. 2007;34(3):181–91.
IEEE
[1]
H. Peeters et al., “CARD15 variants determine a disturbed early response of monocytes to adherent-invasive Escherichia coli strain LF82 in Crohn’s disease,” INTERNATIONAL JOURNAL OF IMMUNOGENETICS, vol. 34, no. 3, pp. 181–191, 2007.
@article{372631,
  abstract     = {{Caspase activation and recruitment domain 15 (CARD15) and Toll-like receptor 4 (TLR4) are respectively intracellular and membrane-bound receptors for bacterial cell wall components [respectively muramyl dipeptide (MDP) and lipopolysaccharide ( LPS)]. Polymorphisms in CARD15 and TLR4 have been linked with Crohn's disease (CD). Adherent-invasive Escherichia coli (AIEC) strains with particular adhesion and invasion characteristics have been specifically associated with CD ileal mucosa. The aim of this study was to investigate the functional impact of these polymorphisms on monocytes in patients with CD, in response to MDP, LPS and AIEC strain LF82. Monocytes were isolated from 40 patients with CD using magnetic cell sorting, stimulated with LPS or MDP or infected with AIEC. IL-1 beta, IL-6, IL-8, IL-10, IL-12 and tumour necrosis factor alpha induction was assessed using quantitative real time-polymerase chain reaction, Cytometric Bead Array and ELISA. Bacterial intracellular survival and replication was assessed using a gentamicin protection assay. Results were linked with the presence of CARD15 and TLR4 polymorphisms. Monocytes of patients with CARD15 polymorphisms showed an early reduced cytokine response (IL-1 beta, IL-6 and IL-10) to infection with AIEC, which was restored after 20 h. A gene-dose effect was seen, comparing wild-types, heterozygotes and homozygotes. We found no differences in intracellular survival and replication of AIEC. Heterozygous carriage of TLR4 polymorphisms did not influence monocyte response. In conclusion, patients with CD carrying CARD15 polymorphisms show a disturbed early inflammatory monocyte response after infection with AIEC strain LF82. For the first time, a functional defect was detected in single heterozygous carriers. These findings reflect the potential role of a genetically altered host response to disease-related bacteria in the pathogenesis of CD.}},
  author       = {{Peeters, Harald and Bogaert, Sara and Laukens, Debby and Rottiers, Pieter and De Keyser, Filip and Darfeuille-Michaud, A and Glasser, AL and Elewaut, Dirk and De Vos, Martine}},
  issn         = {{1744-3121}},
  journal      = {{INTERNATIONAL JOURNAL OF IMMUNOGENETICS}},
  keywords     = {{INFLAMMATORY-BOWEL-DISEASE,NF-KAPPA-B,ILEAL MUCOSA,ADAPTIVE IMMUNITY,NEOTERMINAL ILEUM,INTERFERON-GAMMA,NOD2,LIPOPOLYSACCHARIDE,MUTATIONS,EXPRESSION}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{181--191}},
  title        = {{CARD15 variants determine a disturbed early response of monocytes to adherent-invasive Escherichia coli strain LF82 in Crohn's disease}},
  url          = {{http://dx.doi.org/10.1111/j.1744-313X.2007.00670.x}},
  volume       = {{34}},
  year         = {{2007}},
}

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