Article

Clostridium difficile toxin B is an inflammatory enterotoxin in human intestine.

Developmental Gastroenterology Laboratory, Combined Program in Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital and Harvard Medical School, 114 16th Street, Charlestown, Massachusetts 02129, USA.
Gastroenterology (impact factor: 11.68). 08/2003; 125(2):413-20. pp.413-20
Source: PubMed

ABSTRACT Clostridium difficile causes antibiotic-associated diarrhea and pseudomembranous colitis, diseases afflicting millions of people each year. Although C. difficile releases 2 structurally similar exotoxins, toxin A and toxin B, animal experiments suggest that only toxin A mediates diarrhea and enterocolitis. However, toxin A-negative/toxin B-positive strains of C. difficile recently were isolated from patients with antibiotic-associated diarrhea and colitis, indicating that toxin B also may be pathogenic in humans.
Here we used subcutaneously transplanted human intestinal xenografts in immunodeficient mice to generate a chimeric animal model for C. difficile toxin-induced pathology of human intestine.
We found that intraluminal toxin B, like equivalent concentrations of toxin A, induced intestinal epithelial cell damage, increased mucosal permeability, stimulated interleukin (IL)-8 synthesis, and caused an acute inflammatory response characterized by neutrophil recruitment and tissue damage. Laser capture microdissection and real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) showed that intestinal epithelial cell-specific IL-8 gene expression also was increased significantly after luminal exposure to C. difficile toxins in vivo.
We conclude that C. difficile toxin B, like toxin A, is a potent inflammatory enterotoxin for human intestine. Future therapeutic or vaccine strategies for C. difficile infection therefore need to target both toxins.

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Keywords

animal experiments
 
C. difficile
 
C. difficile infection
 
C. difficile releases 2 structurally similar exotoxins
 
C. difficile toxin B
 
C. difficile toxin-induced pathology
 
C. difficile toxins
 
chimeric animal model
 
Clostridium difficile causes antibiotic-associated diarrhea
 
diseases afflicting millions
 
equivalent concentrations
 
human intestinal xenografts
 
immunodeficient mice
 
induced intestinal epithelial cell damage
 
luminal exposure
 
neutrophil recruitment
 
potent inflammatory enterotoxin
 
tissue damage
 
toxin A-negative/toxin B-positive strains
 
vaccine strategies