Format

Send to

Choose Destination
Cell Host Microbe. 2018 Apr 11;23(4):470-484.e7. doi: 10.1016/j.chom.2018.03.004. Epub 2018 Apr 5.

Listeria Adhesion Protein Induces Intestinal Epithelial Barrier Dysfunction for Bacterial Translocation.

Author information

1
Molecular Food Microbiology Laboratory, Department of Food Science, Purdue University, West Lafayette, IN 47907, USA.
2
Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA.
3
Departments of Pathology and Medicine (Gastroenterology), Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
4
Molecular Food Microbiology Laboratory, Department of Food Science, Purdue University, West Lafayette, IN 47907, USA; Department of Comparative Pathobiology, Purdue University, West Lafayette, IN 47907, USA. Electronic address: bhunia@purdue.edu.

Abstract

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.

KEYWORDS:

Hsp60; InlA; LAP; Listeria monocytogenes; MLCK; NF-κB; bacterial translocation; intestinal epithelial barrier; mouse; tight junction

PMID:
29606495
DOI:
10.1016/j.chom.2018.03.004
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center