4.1 Article

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

Journal

PATHOGENS AND DISEASE
Volume 73, Issue 3, Pages -

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/femspd/ftv008

Keywords

Clostridium difficile; TcdB; epithelial cells; dendritic cells; inflammation

Funding

  1. National Institute of Allergy and Infectious Diseases [R01AI088748, R01DK084509, R56AI99458, U19 AI109776]
  2. National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health (NIH)

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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-alpha 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.

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