Gamma interferon limits access of Listeria monocytogenes to the macrophage cytoplasm

The effect of rIFN-gamma and rTNF on the fate of hemolytic and nonhemolytic (hly-) Listeria monocytogenes in cultured mouse peritoneal macrophages was investigated. In untreated macrophages, approximately 80% of the hemolytic bacteria were killed during the first 2 h of incubation, but the survivors doubled between two and three times. In rIFN-gamma-treated macrophages, although the bacterial killing was identical to the controls during the first 2 h, there was no subsequent bacterial growth, and bactericidal activity continued for the duration of the experiment. rTNF has no affect by itself, but acted synergistically with rIFN-gamma to promote bacterial killing. Infected macrophages with or without rIFN-gamma were examined by EM. The results clearly showed that the role of rIFN-gamma was to prevent access of L. monocytogenes to the macrophage cytoplasm, which would prevent cell-to-cell spread of the bacteria. In addition, rIFN-gamma-treated macrophages exhibited enhanced digestive capacity of the intracellular bacteria.