CD40/CD154 ligation is required for the development of acute ileitis following oral infection with an intracellular pathogen in mice.
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.
Li
Wen
W
Department of Medicine, Dartmouth Medical School, Lebanon, New Hampshire, USA.
Buzoni-Gatel
Dominique
D
Debbabi
Hajer
H
Hu
Mark S
MS
Mennechet
Franck J D
FJ
Durell
Brigit G
BG
Noelle
Randolph J
RJ
Kasper
Lloyd H
LH
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
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D016207:Cytokines; D023201:CD40 Ligand