A role for tryptophan in immune control of chlamydial abortion in sheep

Tryptophan (Trp) catabolism appears to be an important mechanism for regulation of inflammatory responses, resulting in T-cell tolerance and survival of semi-allogeneic concepti during pregnancy. Trp catabolism can be induced by IFN-gamma, and is therefore an important host defence mechanism against intracellular pathogens. Chlamydophila abortus is a bacterial pathogen that can cause persistent infection in non-pregnant sheep, but invades the placenta and causes abortion in late pregnancy. IFN-gamma was found to control the growth of Chlamydophila abortus in ovine cells in a highly dose-dependent manner. Addition of 200U/ml IFN-gamma eradicated all traces of infection from the cultures, whereas concentrations less than 50U/ml failed to control the growth of the organism, resulting in cell lysis. However, concentrations in the range of 50-100U/ml were found to restrict growth to an extent that a persistent infection was established, allowing survival of the organism in tissue culture for several months. Removal of IFN-gamma resulted in the re-appearance of infectious organisms. Addition of exogenous Trp to the cells treated with 50-100U/ml IFN-gamma prevented the establishment of persistence. These effects in tissue culture are analogous to the persistent infection observed in pregnant sheep prior to abortion. These data suggest that control of C. abortus growth in the periphery is linked to the balance of pro-inflammatory cytokine production and availability of Trp during pregnancy.