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A role for membrane-bound CD147 in NOD2-mediated recognition of bacterial cytoinvasion
Andreas Till1, Philip Rosenstiel, Karen Bräutigam
1Institute for Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstr 12, Kiel, Germany.
Abstract:
NOD2 is an intracellular receptor for the bacterial cell wall component muramyl dipeptide. Mutations in the leucine-rich repeat region of NOD2, which lead to an impaired recognition of muramyl dipeptide, have been associated with chronic inflammatory diseases of barrier organs such as Crohn disease, asthma and atopic eczema. In this study we identify CD147 (also known as BSG and EMMPRIN), a membrane-bound regulator of cellular migration, differentiation and inflammatory processes, as a protein interaction partner of NOD2. We demonstrate a complex influence of the CD147-NOD2 interaction on NOD2-dependent signaling responses. We show that CD147 itself acts as an enhancer of the invasion of Listeria monocytogenes, an intracellular bacterial pathogen. We propose that the CD147-NOD2 interaction serves as a molecular guide to regulate NOD2 function at sites of pathogen invasion.
Insights
NOD2 receptor mutations link to inflammatory diseases. This study identifies CD147 as a NOD2 partner, influencing its signaling and enhancing bacterial invasion, potentially guiding NOD2 function during infection.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- NOD2 is an intracellular receptor recognizing bacterial muramyl dipeptide.
- NOD2 mutations are linked to inflammatory diseases like Crohn disease, asthma, and atopic eczema.
- CD147 (BSG/EMMPRIN) regulates cell migration, differentiation, and inflammation.
Purpose of the Study:
- To identify protein interaction partners of NOD2.
- To investigate the functional impact of the CD147-NOD2 interaction on NOD2 signaling.
- To determine CD147's role in bacterial invasion.
Main Methods:
- Protein-protein interaction studies to identify CD147 as a NOD2 partner.
- Analysis of NOD2-dependent signaling pathways.
- Assays to evaluate the effect of CD147 on Listeria monocytogenes invasion.
Main Results:
- CD147 was identified as a novel interaction partner of NOD2.
- The CD147-NOD2 interaction exhibits a complex regulatory effect on NOD2 signaling.
- CD147 enhances the invasion of Listeria monocytogenes into host cells.
Conclusions:
- The CD147-NOD2 interaction modulates NOD2's role in innate immunity.
- CD147 may act as a crucial regulator of NOD2 function at pathogen entry sites.
- This interaction offers a potential target for managing inflammatory diseases and infections.
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