The proteins of the innate immune system provide animals with a first-line defence against bacterial attack by identifying molecular motifs that are characteristic of prokaryotes. The cytosolic innate immune receptor NOD2 binds to muramyl dipeptide – a component of the bacterial peptidoglycan-based cell wall – and triggers a signalling cascade that activates NF-κB and stimulates interleukin production. On page 487, Stefan Schreiber and colleagues identify the transmembrane receptor CD147 as a novel regulator of NOD2 activity. By using bacterial two-hybrid screening and co-immunoprecipitation, the authors demonstrate that CD147 binds directly to the two CARD domains of NOD2, and that the two proteins partially colocalise at the plasma membrane. The authors show that CD147 – which is upregulated in response to infection – decreases NOD2-dependent activation of NF-κB and interleukin release. Moreover, CD147 promotes the invasion of Listeria bacteria into epithelial cells. The authors propose that CD147 exerts its effects by inhibiting the binding of the effector protein RIP2 to the CARD domains of NOD2. These results implicate CD147 as a modulator of the innate immune response.
- © The Company of Biologists Limited 2008