Long-term effects of gamma interferon on chlamydia-infected host cells: microbicidal activity follows microbistasis

When human monocyte-derived macrophages or a human uroepithelial cell line (T24 cells) was incubated in the presence of gamma interferon (IFN-gamma) for 24 to 48 h and then infected with Chlamydia psittaci, host cells became activated to restrict intracellular C. psittaci growth. A reversal of this inhibition was observed when infected cells were supplemented with excess exogenous tryptophan at the time of infection or at 1 to 3 days after infection. When IFN-gamma-treated, infected cells were incubated for more extended periods of time before the addition of exogenous tryptophan, no recovery of viable chlamydiae was observed. Neither replacement of the IFN-gamma-containing medium with complete medium supplemented with excess tryptophan nor the addition of excess concentrations of all 20 amino acids with and without essential vitamins contributed to the reversal of IFN-gamma-mediated inhibition of chlamydial growth beyond the time when reversal occurred after the addition of exogenous tryptophan alone. These data provide evidence which indicates that although IFN-gamma treatment of host cells initially results in a microbistatic inhibition of intracellular chlamydial development, longer incubations result in microbicidal activity that is irreversible by modulation of essential nutrient levels.