Exploitation of host cell cytoskeleton and signalling during Listeria monocytogenes entry into mammalian cells

Deciphering how Listeria monocytogenes exploits the host cell machinery to invade mammalian cells during infection is a key issue for the understanding how this food-borne pathogen causes a pleiotropic disease ranging from gastro-enteritis to meningitis and abortions. Using multidisciplinary approaches, essentially combining bacterial genetics and cell biology, we have identified two bacterial proteins critical for entry into target cells, In1A and In1B. Their cellular ligands have been also identified: In1A interacts with the adhesion molecule E-cadherin, while In1B interacts with the receptor for the globular head of the complement factor C1q (gC1q-R), with the hepatocyte growth factor receptor (c-Met) and with glycosaminoglycans (including heparan sulphate). The dynamic interaction between these cellular receptors and the actin cytoskeleton is currently under investigation. Several intracellular molecules have been recognized as key effectors for Listeria entry into target cells, including catenins (implicated in the connection of E-cadherin to actin) and the actin depolymerising factor/cofilin (involved in the rearrangement of the cytoskeleton in the In1B-dependent internalisation pathway). At the organism level, species specificity has been discovered concerning the interaction between In1A and E-cadherin, leading to the generation of transgenic mice expressing the human E-cadherin, in which the critical role of In1A in the crossing of the intestinal barrier has been clearly determined. Listeria appears as an instrumental model for addressing critical questions concerning both the complex process of bacterial pathogenesis and also fundamental molecular processes, such as phagocytosis. (C) 2003 Academie des sciences. Published by Elsevier SAS. All rights reserved.