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First published online February 6, 2008
doi: 10.1242/10.1242/jcs.016980

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A role for membrane-bound CD147 in NOD2-mediated recognition of bacterial cytoinvasion

Andreas Till^1,*, Philip Rosenstiel^1,2,*,, Karen Bräutigam¹, Christian Sina³, Gunnar Jacobs¹, Hans-Heinrich Oberg⁴, Dirk Seegert⁵, Trinad Chakraborty⁶ and Stefan Schreiber^1,3,

¹ Institute for Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstr. 12, 24105 Kiel, Germany
² Max-Planck Institute for Molecular Genetics, Berlin, Germany
³ 1st Department for General Internal Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstr. 12, 24105 Kiel, Germany
⁴ Institute of Immunology, University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstr. 12, 24105 Kiel, Germany
⁵ CONARIS Research Institute AG, Kiel, Germany
⁶ Institute for Medical Microbiology and Hygiene, University of Giessen, Germany

Authors for correspondence (e-mails: p.rosenstiel{at}mucosa.de; s.schreiber{at}mucosa.de)

Accepted 18 November 2007

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.

Key words: Inflammation, Crohn disease, Protein interaction, CD147 (BSG, EMMPRIN), NOD2 (CARD15), Cytoinvasion, Listeria monocytogenes

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