A role for membrane-bound CD147 in NOD2-mediated recognition of bacterial cytoinvasion.
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.
Till
Andreas
A
Institute for Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Schittenhelmstr 12, Kiel, Germany.
Rosenstiel
Philip
P
Bräutigam
Karen
K
Sina
Christian
C
Jacobs
Gunnar
G
Oberg
Hans-Heinrich
HH
Seegert
Dirk
D
Chakraborty
Trinad
T
Schreiber
Stefan
S
D051926:Basigin / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D016209:Interleukin-8 / Q000378:metabolism; D008089:Listeria monocytogenes / Q000166:cytology / Q000254:growth & development*; D016328:NF-kappa B / Q000378:metabolism; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020798:Two-Hybrid System Techniques
D016207:Cytokines; D016209:Interleukin-8; D016328:NF-kappa B; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D051926:Basigin