Involvement of CD44v6 in InlB‐dependent Listeria invasion

Summary Listeria monocytogenes , a Gram‐positive bacterium, is the causative agent for the disease called listeriosis. This pathogen utilizes host cell surface proteins such as E‐cadherin or c‐Met in order to invade eukaryotic cells. The invasion via c‐Met depends on the bacterial protein InlB that activates c‐Met phosphorylation and internalization mimicking in many regards HGF, the authentic c‐Met ligand. In this paper, we demonstrate that the activation of c‐Met induced by InlB is dependent on CD44v6, a member of the CD44 family of transmembrane glycoproteins. Inhibiting CD44v6 by means of a blocking peptide, a CD44v6 antibody or CD44v6‐specific siRNA prevents the activation of c‐Met induced by InlB. Subsequently, signalling, scattering and the entry of InlB‐coated beads into host cells are also impaired by CD44v6 blocking reagents. For the entry process, ezrin, a protein that links the CD44v6 cytoplasmic domain to the cytoskeleton, is required as well. Most importantly, this collaboration between c‐Met and CD44v6 contributes to the invasion of L. monocytogenes into target cells as demonstrated by a drastic decrease in bacterial invasion in the presence of blocking agents such as the CD44v6 peptide or antibody.