Related Experiment Video

Updated: Jul 11, 2026

High-throughput Flow Cytometry Cell-based Assay to Detect Antibodies to N-Methyl-D-aspartate Receptor or Dopamine-2 Receptor in Human Serum
10:19

High-throughput Flow Cytometry Cell-based Assay to Detect Antibodies to N-Methyl-D-aspartate Receptor or Dopamine-2 Receptor in Human Serum

Published on: November 23, 2013

Muramyl dipeptide and toll-like receptor sensitivity in NOD2-associated Crohn's disease

David A van Heel1, Subrata Ghosh, Matt Butler

  • 1Intestinal Inflammation and Repair Group, Department of Gastroenterology, Imperial College London, UK. d.vanheel@imperial.ac.uk

Lancet (London, England)
|May 25, 2005
PubMed

Insights

Mutations in NOD2 (CARD15) affect Crohn's disease by impairing immune cell responses to muramyl dipeptide (MDP). This suggests a deficiency in early immune priming and provides a basis for a NOD2 functional test.

Area of Science:

  • Immunology
  • Gastroenterology
  • Genetics

Background:

  • NOD2 (CARD15) mutations are common in Crohn's disease, but their functional impact on immune responses remains unclear.
  • NOD2 is a key receptor for muramyl dipeptide (MDP), a component of bacterial cell walls.

Purpose of the Study:

  • To investigate the functional consequences of NOD2 mutations on cytokine production in response to MDP.
  • To explore the interplay between NOD2 and Toll-like receptor (TLR) signaling pathways in Crohn's disease.

Main Methods:

  • Peripheral blood mononuclear cells (PBMCs) from patients and controls were stimulated with MDP and/or TLR ligands.
  • Cytokine secretion (TNF-alpha, IL-1beta, IL-8) was measured using ELISAs or similar assays.
  • The effects of common NOD2 mutations on these responses were analyzed.

Main Results:

  • MDP alone induced significant interleukin-8 (IL-8) secretion but minimal TNF-alpha or IL-1beta.
  • MDP potentiated TNF-alpha and IL-1beta responses to TLR ligands.
  • These MDP-induced effects were abolished in cells with common NOD2 double mutant genotypes, particularly at low MDP concentrations.

Conclusions:

  • Common NOD2 mutations impair immune responses to MDP, affecting IL-8 production and cross-talk with TLR pathways.
  • These findings suggest a defect in early immune priming in Crohn's disease patients with NOD2 mutations.
  • The observed functional deficiency provides a basis for developing a diagnostic test for NOD2 functional deficiency.

More Related Videos

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

Two Flow Cytometric Approaches of NKG2D Ligand Surface Detection to Distinguish Stem Cells from Bulk Subpopulations in Acute Myeloid Leukemia05:24

Two Flow Cytometric Approaches of NKG2D Ligand Surface Detection to Distinguish Stem Cells from Bulk Subpopulations in Acute Myeloid Leukemia

Published on: February 21, 2021

Related Concept Videos

Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Amebiasis01:28

Amebiasis

Entamoeba histolytica, a protozoan parasite, is responsible for intestinal and extraintestinal amebiasis. Though a significant proportion of infections remain asymptomatic, approximately 50 million individuals annually are estimated to present with clinical disease, resulting in up to 100,000 deaths globally. The disease burden is disproportionately high in regions with lower socioeconomic status, such as parts of India, Africa, Mexico, and Latin America.Etiology and TransmissionThe infective...
Inflammatory Bowel Disease II: Ulcerative Colitis01:20

Inflammatory Bowel Disease II: Ulcerative Colitis

Ulcerative colitis is a chronic inflammatory disorder of the colon characterized by continuous mucosal inflammation that typically begins in the rectum and extends proximally in a uniform pattern. Its pathogenesis involves a complex interplay of genetic predisposition, immune dysregulation, and environmental influences. These factors converge to impair the colon’s epithelial defenses and promote an exaggerated inflammatory response against luminal contents.Breakdown of the Mucosal BarrierA...
Inflammatory Bowel Disease III: Crohn's Disease01:25

Inflammatory Bowel Disease III: Crohn's Disease

Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...