Publication date: Available online 5 April 2018
Source:Cell Host & Microbe
Author(s): Rishi Drolia, Shivendra Tenguria, Abigail C. Durkes, Jerrold R. Turner, Arun K. Bhunia
Intestinal epithelial cells are the first line of defense against enteric pathogens, yet bacterial pathogens, such as Listeria monocytogenes, can breach this barrier. We show that Listeria adhesion protein (LAP) induces intestinal epithelial barrier dysfunction to promote bacterial translocation. These disruptions are attributed to the production of pro-inflammatory cytokines TNF-α and IL-6, which is observed in mice challenged with WT and isogenic strains lacking the surface invasion protein Internalin A (ΔinlA), but not a lap— mutant. Additionally, upon engagement of its surface receptor Hsp60, LAP activates canonical NF-κB signaling, facilitating myosin light-chain kinase (MLCK)-mediated opening of the epithelial barrier via cellular redistribution of the epithelial junctional proteins claudin-1, occludin, and E-cadherin. Pharmacological inhibition of MLCK or NF-κB in cells or genetic ablation of MLCK in mice prevents mislocalization of junctional proteins and L. monocytogenes translocation. Thus, L. monocytogenes uses LAP to exploit epithelial defenses and cross the intestinal epithelial barrier.
Graphical abstract
Teaser
The pathogen Listeria monocytogenes crosses the intestinal barrier during infection. Drolia et al. show that L. monocytogenes employs Listeria adhesion protein (LAP) to exploit epithelial innate defenses and induce intestinal barrier dysfunction. LAP induces activation of NF-κB and MLCK, resulting in cellular redistribution of epithelial junction proteins and bacterial translocation.https://ift.tt/2GHobO5
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