Listeriaadhesion protein orchestrates caveolae-mediated apical junctional remodeling of epithelial barrier forL. monocytogenestranslocation

Abstract

ABSTRACTThe cellular junctional architecture remodeling by LAP-Hsp60 interaction forL. monocytogenes(Lm) passage through the epithelial barrier is incompletely understood. Here, using the gerbil model, permissive to internalin (Inl) A/B-mediated pathways like in humans, we demonstrate thatLmcrosses the intestinal villi at 48 h post-infection. In contrast, the single isogenic (lap─or ΔinlA) or double (lap─ΔinlA) mutant strains show significant defects. LAP promotesLmtranslocation via endocytosis of cell-cell junctional complex in enterocytes that do not display luminal E-cadherin. In comparison, InlA-mediated transcytosis occurs in enterocytes displaying apical E-cadherin during cell extrusion and mucus expulsion from goblet cells. LAP hijacks caveolar endocytosis to traffic integral junctional proteins to the early and recycling endosomes. Pharmacological inhibition in a cell line and genetic knock-out of caveolin-1 in mice prevents LAP-induced intestinal permeability, junctional endocytosis, andLmtranslocation. Furthermore, LAP-Hsp60-dependent tight junction remodeling is also necessary for InlA access to E-cadherin forLmintestinal barrier crossing in InlA-permissive hosts.