CELL-PROLIFERATION ENHANCES ENTRY OF LISTERIA-MONOCYTOGENES INTO INTESTINAL EPITHELIAL-CELLS BY 2 PROLIFERATION-DEPENDENT ENTRY PATHWAYS

Bacterial entry into intestinal host cells is the result of a fairly s ophisticated manipulation of host cell machinery by the pathogens, To study further the potential cell target of Lister in spp., the in-vitr o entry of L. monocytogenes strains into intestinal cells was examined in relation to the metabolism, proliferation and differentiation of t he cells by the alamarBlue assay, [H-3] thymidine incorporation, and b rush border-associated enzyme activities, respectively, The study show ed that cell metabolism was not involved in the entry of L. monocytoge nes in three cell models (two human and one porcine). On the other han d, entry was closely related to the proliferation process and poorly r elated to the differentiation state of the cells, The use of L. monocy togenes mutants lacking invasion proteins showed that InlA and InlB ac ted in synergy to mediate the entry of L. monocytogenes into prolifera tive cells, whereas InlA alone seemed to be involved in the entry into non-proliferative cells, These two entry pathways could correspond to the two cellular processes used by L. monocytogenes to enter prolifer ative and non-proliferative cells, as suggested by the use of cytochal asin D, nocodazole, chloroquine and monodansylcadaverine. Taken togeth er, we propose a hypothesis in which the entry of L. monocytogenes is mediated by interaction between randomly distributed E-cadherin on the surface of proliferative cells, Tn contrast, the entry into non-proli ferative cells may involve pp60(c-src), a proto-oncogenic tyrosine kin ase signal that modifies E-cadherin localisation, In conclusion, these results suggest that L. monocytogenes may preferentially enter crypt cells in vivo by a microfilament-dependent process, whereas the few ba cteria that infect villus cells enter by an E-cadherin-internalin inte raction that mediates microtubule-dependent endocytosis.