CD40/CD154 ligation is required for the development of acute ileitis following oral infection with an intracellular pathogen in mice

Gastroenterology. 2002 Mar;122(3):762-73. doi: 10.1053/gast.2002.31888.

Abstract

Background & aims: Acute inflammatory ileitis occurs in C57BL/6 mice after oral infection with Toxoplasma gondii. We evaluated the role of CD40/CD154 interaction in the development of acute ileitis in this experimental model.

Methods: CD154-/- and anti-CD154 antibody-treated mice as well as chimeric mice, either C57BL/6 or CD40-/- reconstituted with bone marrow from C57BL/6 or CD40-/- mice, were orally infected with cysts. Inflammation was assessed by qualitative histologic and phenotypic analysis of the intestinal compartment at day 7 after infection. Intestinal chemokine and cytokine production was assayed by ribonuclease protection assay.

Results: CD154-/- and anti-CD154 monoclonal antibody-treated mice failed to develop an acute, lethal ileitis after oral infection and survived. Chimeric mice reconstituted with bone marrow from C57BL/6 mice developed ileitis and died, whereas those recipient mice deficient in CD40 survived. CD40 expression in the intestine after infection was found principally within the B-cell compartment. A modest increase in CD40 expression in both the macrophage and dendritic cell compartments was also observed. Both chemokine and cytokine expression was up-regulated in those recipients of wild-type bone marrow. Impairment of CD40/CD154 interaction abrogated the production of these proinflammatory productions.

Conclusions: CD40/CD154 interaction is essential to the development of inflammation in this pathogen-driven experimental model of acute ileitis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • CD40 Antigens / genetics
  • CD40 Antigens / metabolism*
  • CD40 Ligand / immunology
  • CD40 Ligand / metabolism*
  • Cytokines / immunology
  • Ileitis / immunology
  • Ileitis / metabolism
  • Ileitis / parasitology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenotype
  • Toxoplasma / immunology*
  • Toxoplasmosis / immunology*
  • Toxoplasmosis / metabolism
  • Toxoplasmosis / pathology

Substances

  • Antibodies, Monoclonal
  • CD40 Antigens
  • Cytokines
  • CD40 Ligand