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

First Author  Li W Year  2002
Journal  Gastroenterology Volume  122
Issue  3 Pages  762-73
PubMed ID  11875009 Mgi Jnum  J:75019
Mgi Id  MGI:2159554 Doi  10.1053/gast.2002.31888
Citation  Li W, et al. (2002) CD40/CD154 ligation is required for the development of acute ileitis following oral infection with an intracellular pathogen in mice. Gastroenterology 122(3):762-73
abstractText  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.
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