Clostridium difficile toxin B intoxicated mouse colonic epithelial CT26 cells stimulate the activation of dendritic cells

Pathog Dis. 2015 Apr;73(3):ftv008. doi: 10.1093/femspd/ftv008. Epub 2015 Jan 27.

Abstract

Clostridium difficile causes antibiotic-associated diarrhea and pseudomembranous colitis mainly through two exotoxins TcdA and TcdB that target intestinal epithelial cells. Dendritic cells (DCs) play an important role in regulating intestinal inflammatory responses. In the current study, we explored the interaction of TcdB-intoxicated epithelial cells with mouse bone marrow-derived DCs. TcdB induced cell death and heat shock protein translocation in mouse intestinal epithelial CT26 cells. The intoxicated epithelial cells promoted the phagocytosis and the TNF-α secretion by DCs. Incubation with TcdB-intoxicated CT26 cells stimulated DC maturation. Moreover, TcdB-treated CT26 cells induced DC immigration when they were injected into mice subcutaneously. Taken together, these data demonstrate that TcdB-intoxicated intestinal epithelial cells are able to stimulate DC activation in vitro and attract DCs in vivo, indicating that epithelial cells may be able to regulate DC activation under the exposure of TcdB during C. difficile infection.

Keywords: Clostridium difficile; TcdB; dendritic cells; epithelial cells; inflammation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Bacterial Proteins / toxicity*
  • Bacterial Toxins / toxicity*
  • Cell Communication*
  • Cell Death / drug effects
  • Cell Differentiation
  • Cell Movement
  • Dendritic Cells / immunology*
  • Dendritic Cells / physiology
  • Epithelial Cells / drug effects*
  • Epithelial Cells / immunology*
  • Epithelial Cells / physiology
  • Heat-Shock Proteins / metabolism
  • Male
  • Mice, Inbred BALB C
  • Phagocytosis
  • Protein Transport
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Bacterial Proteins
  • Bacterial Toxins
  • Heat-Shock Proteins
  • Tumor Necrosis Factor-alpha
  • toxB protein, Clostridium difficile