Listeria monocytogenes Invades the Epithelial Junctions at Sites of Cell Extrusion

Abstract

Listeria monocytogenes causes invasive disease by crossing the intestinal epithelial barrier. This process depends on the interaction between the bacterial surface protein Internalin A and the host protein E-cadherin, located below the epithelial tight junctions at the lateral cell-to-cell contacts. We used polarized MDCK cells as a model epithelium to determine how L. monocytogenes breaches the tight junctions to gain access to this basolateral receptor protein. We determined that L. monocytogenes does not actively disrupt the tight junctions, but finds E-cadherin at a morphologically distinct subset of intercellular junctions. We identified these sites as naturally occurring regions where single senescent cells are expelled and detached from the epithelium by extrusion. The surrounding cells reorganize to form a multicellular junction that maintains epithelial continuity. We found that E-cadherin is transiently exposed to the lumenal surface at multicellular junctions during and after cell extrusion, and that L. monocytogenes takes advantage of junctional remodeling to adhere to and subsequently invade the epithelium. In intact epithelial monolayers, an anti-E-cadherin antibody specifically decorates multicellular junctions and blocks L. monocytogenes adhesion. Furthermore, an L. monocytogenes mutant in the Internalin A gene is completely deficient in attachment to the epithelial apical surface and is unable to invade. We hypothesized that L. monocytogenes utilizes analogous extrusion sites for epithelial invasion in vivo. By infecting rabbit ileal loops, we found that the junctions at the cell extrusion zone of villus tips are the specific target for L. monocytogenes adhesion and invasion. Thus, L. monocytogenes exploits the dynamic nature of epithelial renewal and junctional remodeling to breach the intestinal barrier.

Cited by papers we hold 9

• <named-content content-type="genus-species">Campylobacter jejuni</named-content> Triggers Signaling through Host Cell Focal Adhesions To Inhibit Cell Motility · 2021
  Not checked
• Volume measurement and biophysical characterization of mounds in epithelial monolayers after intracellular bacterial infection · 2021
  Not checked
• Controlling Epithelial Polarity: A Human Enteroid Model for Host-Pathogen Interactions · 2019
  No notice
• Epithelial Cell Shedding and Barrier Function · 2014
  No notice
• Attenuated Listeria monocytogenes: a powerful and versatile vector for the future of tumor immunotherapy · 2014
  No notice
• ActA Promotes Listeria monocytogenes Aggregation, Intestinal Colonization and Carriage · 2013
  No notice
• Helicobacter pylori Perturbs Iron Trafficking in the Epithelium to Grow on the Cell Surface · 2011
  No notice
• Placental Syncytiotrophoblast Constitutes a Major Barrier to Vertical Transmission of Listeria monocytogenes · 2010
  No notice
• Helicobacter pylori Usurps Cell Polarity to Turn the Cell Surface into a Replicative Niche · 2009
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.