Characterization of gamma interferon-mediated cytotoxicity to chlamydia-infected fibroblasts

Addition of murine recombinant gamma interferon (IFN-gamma) to mouse fibroblast cultures infected with Chlamydia psittaci was found to induce a cytotoxic response that was dependent on the concentration of IFN-gamma added and the multiplicity of infection given. No cytotoxicity was observed for uninfected cells treated with IFN-gamma, nor did infection alone elicit cytotoxicity. Cytotoxicity was detected only if IFN-gamma was present for at least the first 18 h of a 30-h incubation period. Cytotoxic activity was not observed when infected cells were treated with 50 micrograms of chloramphenicol per ml, a drug which inhibits differentiation of infectious elementary bodies to noninfectious reticulate bodies. Cytotoxic activity was restored if addition of chloramphenicol was delayed until 18 h postinfection. Addition of 100 U of penicillin per ml to infected host cells reduced but did not abolish cytotoxic activity. Treatment of host cells with as little as 0.2 microgram of cycloheximide per ml inhibited cytotoxicity without interfering with chlamydial growth. When addition of cycloheximide was delayed until 12 h after infection and IFN-gamma treatment, cytotoxicity was restored. These data indicate that IFN-gamma functions as a cytotoxic cytokine against chlamydia-infected fibroblasts. Cytotoxicity was found to be dependent on chlamydial multiplicity of infection, differentiation of chlamydiae to the metabolically active form, and host cell protein synthesis.