CD44-independent activation of the Met signaling pathway by HGF and In1B

Listeria monocytogenes is a facultative intracellular Gram positive bacterium responsible for listeriosis It is able to Invade survive and replicate in phagocytic and non-phagocytic cells The L monocytogenes surface protein In1B interacts with c Met the hepatocyte growth factor (HGF) receptor inducing bacterial internalization in numerous non-phagocytic cells As In1B and HGF are known to trigger similar signaling pathways upon c-Met activation we investigated the role of CD44 and more specifically its isoform CD44v6 in bacterial internalization in non-phagocytic cells Indeed CD44 the hyaluronic acid transmembrane receptor and more specifically its isoform CD44v6 have been reported as necessary for the activation of c-Met upon the interaction with either the endogenous ligand HGF or the L monocyto genes surface protein In1B Our results demonstrate that in the cell lines that we used CD44 receptors play no role in the activation of c Met neither during L monocyto genes entry nor upon HGF activation Furthermore none of the CD44 isoforms was recruited at the L monocytogenes entry site and depletion by siRNA of total CD44 or of CD44v6 isoform did not reduce bacterial infections Conversely the overexpression of CD44 or CD44v6 had no significant effect on L monocytogenes internalization Together our results reveal that the activation of c Met can be largely CD44 independent (C) 2010 Institut Pasteur Published by Elsevier Masson SAS All rights reserved