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Published on: February 21, 2018
CD44-independent activation of the Met signaling pathway by HGF and InlB
Laurent Dortet1, Esteban Veiga, Matteo Bonazzi
1Institut Pasteur, Unité des interactions Bactéries-Cellules, 25 rue du Dr. Roux, 75015 Paris, France.
Abstract:
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 InlB interacts with c-Met, the hepatocyte growth factor (HGF) receptor, inducing bacterial internalization in numerous non-phagocytic cells. As InlB 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. monocytogenes surface protein InlB. 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. monocytogenes 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.
Insights
This study investigated the role of CD44 in Listeria monocytogenes internalization. Results show that CD44 and its CD44v6 isoform are not required for bacterial entry or c-Met activation in non-phagocytic cells.
Area of Science:
- Microbiology
- Cell Biology
- Immunology
Background:
- Listeria monocytogenes is a pathogen causing listeriosis.
- The surface protein InlB facilitates bacterial entry into host cells by interacting with the c-Met receptor.
- CD44, a hyaluronic acid receptor, and its CD44v6 isoform were hypothesized to be crucial for c-Met activation during L. monocytogenes invasion.
Purpose of the Study:
- To investigate the role of CD44 and its CD44v6 isoform in Listeria monocytogenes internalization into non-phagocytic cells.
- To determine if CD44 is involved in the activation of the c-Met signaling pathway by L. monocytogenes InlB or hepatocyte growth factor (HGF).
Main Methods:
- Utilized cell lines to study bacterial internalization.
- Employed siRNA to deplete CD44 and CD44v6 expression.
- Assessed c-Met activation and CD44 isoform recruitment at the bacterial entry site.
- Investigated the effect of CD44 and CD44v6 overexpression on bacterial internalization.
Main Results:
- CD44 receptors did not play a role in c-Met activation during L. monocytogenes entry or HGF stimulation.
- No CD44 isoforms were recruited to the site of L. monocytogenes entry.
- Depletion of CD44 or CD44v6 did not reduce bacterial infections.
- Overexpression of CD44 or CD44v6 had no significant impact on L. monocytogenes internalization.
Conclusions:
- The activation of the c-Met receptor by L. monocytogenes or HGF is largely independent of CD44.
- CD44 and its CD44v6 isoform are not essential for L. monocytogenes internalization into the tested non-phagocytic cells.
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