Lean, I.S.; McDonald, S.A.C.; McDonald, V.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA56
Academic Journal
Introduction: It has been suggested that TNF-α may play a role in immunity to infection by the intracellular parasite C parvum. Increased mucosal expression of this pro-inflammatory cytokine has been noted in the intestine of infected mice and humans whilst exogenous TNFα has been shown to reduce oocyst shedding in susceptible mouse models. However, its exact mechanisms of action and its importance in infection have yet to be established. Methods: The human enterocyte cell lines HT 29, Caco2 and the mouse enterocyte cell line CMT 93 were pre-incubated for 24 h with TNFα prior to infection with Cparvum. Cells were incubated for a further 24 h then fixed and stained in Giemsa and the number of parasites estimated per 50 high power fields. Using previously established in vitro models of infection, the possible mechanisms of action involved were also studied. Finally, C57BL/6 TNFα deficient neonatal mice were infected with C parvum and the outcome of disease measured. Results: TNFα inhibited the development of C parvum in all 3 enterocyte cell lines. In HT 29 cells TNFα led to a 29 (+/-10)% decrease in parasite numbers in concentrations as Iow as 0.04 ng/ml. One mechanism identified was the inhibition of invasion. Tryptophan depletion and alteration of intracellular iron did not appear to be involved. In the murine model of infection however, no significant difference was noted in either the course of infection or parasite burden between controls and mice lacking the functional gene for TNFα. Conclusion: We have demonstrated that TNFα inhibits C parvum development in enterocytes. We have also identified, for the first time, a possible mechanism of its action. Although TNFα appears to have an inhibitory effect in vitro, it does not appear to be essential for recovery against infection in an in vivo mouse model.


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