Genetic deficiency in the chemokine receptor CCR1 protects against acute Clostridium difficile toxin A enteritis in mice

Gastroenterology. 2002 Mar;122(3):725-33. doi: 10.1053/gast.2002.31873.


Background & aims: The role of the CC chemokine receptor (CCR) 1 in acute enteritis was investigated by subjecting CCR1 knockout mice to Clostridium difficile toxin A treatment.

Methods: Toxin A or vehicle was injected into ileal loops in anesthetized wild-type, CCR1-/- and macrophage inhibitory protein (MIP)-1alpha-/- mice. After 1-4 hours, fluid accumulation was calculated, and the loops were processed for histology, myeloperoxidase activity, regulated on activation, normal T cell expressed and secreted (RANTES) production, and messenger RNA measurements.

Results: Toxin A induced in all mice a significant (P < 0.05) increase in ileal fluid accumulation, epithelial damage, and neutrophil infiltration, with all parameters being significantly (P < 0.01) lower in CCR1-/- and MIP-1alpha-/- mice. Ileal messenger RNA expression of the CCR1 ligands MIP-1alpha and RANTES and RANTES synthesis were increased in toxin A-treated wild-type mice. The RANTES antagonist Met-RANTES significantly (P < 0.01) reduced the toxin A-induced increases in ileal fluid accumulation and myeloperoxidase activity in wild-type mice.

Conclusions: C. difficile toxin A-induced murine enteritis involves CCR1 and its ligands MIP-1alpha and RANTES, which may be important mediators of the neutrophil recruitment characterizing acute, enterotoxin-mediated enteritis.

MeSH terms

  • Acute Disease
  • Animals
  • Bacterial Toxins / toxicity*
  • Body Fluids / metabolism
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5 / analogs & derivatives*
  • Chemokine CCL5 / antagonists & inhibitors
  • Chemokine CCL5 / pharmacology
  • Cholera Toxin / toxicity
  • Enterocolitis / chemically induced
  • Enterocolitis / immunology*
  • Enterocolitis / pathology
  • Enterotoxins / toxicity*
  • Gene Expression / immunology
  • Ileum / metabolism
  • Ileum / pathology
  • Macrophage Inflammatory Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • RNA, Messenger / analysis
  • Receptors, CCR1
  • Receptors, Chemokine / genetics*


  • Bacterial Toxins
  • Ccr1 protein, mouse
  • Chemokine CCL3
  • Chemokine CCL4
  • Chemokine CCL5
  • Enterotoxins
  • Macrophage Inflammatory Proteins
  • RANTES, Met-
  • RNA, Messenger
  • Receptors, CCR1
  • Receptors, Chemokine
  • tcdA protein, Clostridium difficile
  • Cholera Toxin