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Caspase recruitment domain-containing protein 8 (CARD8) negatively regulates NOD2-mediated signaling

Oliver von Kampen1, Simone Lipinski, Andreas Till

  • 1Institute of Clinical Molecular Biology, Christian Albrechts University, Kiel D-24105, Germany.

The Journal of Biological Chemistry
|April 14, 2010
PubMed

Insights

Caspase activating and recruitment domain 8 (CARD8) regulates NOD2 signaling in intestinal cells. CARD8 inhibits NOD2-induced inflammation and bacterial killing, acting as a molecular switch for innate immunity.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Caspase activating and recruitment domain 8 (CARD8) is known to regulate inflammatory and apoptotic pathways.
  • NOD2 is a key pattern recognition receptor involved in sensing bacterial components and initiating immune responses.

Purpose of the Study:

  • To investigate the specific role of CARD8 in modulating NOD2 signaling within intestinal epithelial cells.
  • To elucidate the molecular mechanisms by which CARD8 influences NOD2-mediated responses.

Main Methods:

  • Co-immunoprecipitation assays to assess physical interaction between CARD8 and NOD2.
  • Analysis of nodosome assembly and downstream signaling events (e.g., NF-κB activation) upon stimulation with muramyl-dipeptide.
  • Assessment of NOD2's bactericidal activity against Listeria monocytogenes in the presence of CARD8.

Main Results:

  • CARD8 physically interacts with NOD2 in intestinal epithelial cells.
  • CARD8 inhibits the assembly of the nodosome complex and subsequent NOD2 signaling.
  • CARD8 attenuates the direct bactericidal effect of NOD2 against intracellular Listeria monocytogenes.

Conclusions:

  • CARD8 acts as a specific inhibitor of NOD2 signaling in intestinal epithelial cells.
  • CARD8 functions as a novel molecular switch for the endogenous regulation of NOD2-dependent inflammatory processes.
  • Understanding the CARD8-NOD2 interaction provides insights into controlling innate immune responses in the gut.

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