Inhibition of Apoptosis by Gamma Interferon in Cells and Mice Infected withChlamydia muridarum(the Mouse Pneumonitis Strain ofChlamydia trachomatis)

Abstract
The effect of gamma interferon (IFN-γ) on apoptosis due to infection byChlamydia muridarum(the mouse pneumonitis strain ofChlamydia trachomatis) was studied in epithelial cells in culture and in the genital tracts of mice. IFN-γ concentrations that induce the formation of aberrant, persistent chlamydiae inhibit apoptosis due toC. muridaruminfection. In cells treated with an IFN-γ concentration that leads to the development of a heterogenous population of normal and aberrantChlamydiavacuoles, apoptosis was inhibited preferentially in cells that contained the aberrant vacuoles. The inhibitory effect of IFN-γ appears to be due in part to expression of host cell indoleamine 2,3-dioxygenase activity, since inhibition of apoptosis could be partially reversed through coincubation with exogenous tryptophan. Apoptotic cells were observed in the genital tracts of wild-type mice infected withC. muridarum, and a significantly larger number of apoptotic cells was detected in infected IFN-γ-deficient mice. These results suggest that IFN-γ may contribute to pathogenesis of persistentChlamydiainfections in vivo by preventing apoptosis of infected cells.