title: CD40/CD154 ligation is required for the development of acute ileitis following oral infection with an intracellular pathogen in mice.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Medicine, Dartmouth Medical School, Lebanon, New Hampshire, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Dominique
authors.initials: D
authors.lastname: Buzoni-Gatel
authors.forename: Hajer
authors.initials: H
authors.lastname: Debbabi
authors.forename: Mark S
authors.initials: MS
authors.lastname: Hu
authors.forename: Franck J D
authors.initials: FJ
authors.lastname: Mennechet
authors.forename: Brigit G
authors.initials: BG
authors.lastname: Durell
authors.forename: Randolph J
authors.initials: RJ
authors.lastname: Noelle
authors.forename: Lloyd H
authors.initials: LH
authors.lastname: Kasper
mesh_terms: D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism*; D023201:CD40 Ligand / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology; D007079:Ileitis / Q000276:immunology / Q000378:metabolism / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D014122:Toxoplasma / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D016207:Cytokines; D023201:CD40 Ligand