Gamma interferon activates human macrophages to become tumoricidal and leishmanicidal but enhances replication of macrophage-associated mycobacteria

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Abstract
Recombinant human gamma interferon (rIFN-.gamma.) was examined for its ability to activate human peripheral blood monocyte-derived macrophages to kill tumor cells and to affect the replication of two phylogenetically distinct intracellular pathogens, Mycobacterium tuberculosis and Leishmania donovani. Macrophages preincubated overnight with doses of rIFN-.gamma. from 5 to 500 U/ml killed [3H]thymidine-labeled mouse L929 tumor targets, as measured by the release of [3H]thymidine into the supernatant after 48 h. Counts of macrophages initially infected with leishmania promastigotes showed that rIFN-.gamma.-pretreated macrophages could both inhibit the replication of and kill the resulting intramacrophage amastigotes over a 7-day period. However, rIFN-.gamma. pretreatment of macrophages actually enhanced mycobacterial replication over a 5- to 7-day period, as assessed by (i) counting acid-fast bacilli or (ii) lysing macrophages to release bacteria and determining the numbers of viable units. Mycobacterial growth was not affected by rIFN-.gamma. in the absence of macrophages. rIFN-.gamma. pretreatment had opposite effects on the uptake of mycobacteria and leishmania. As many as 80% fewer activated macrophages ingested mycobacteria compared with controls, whereas 50% more activated macrophages were infected with leishmania. These results suggest that rIFN-.gamma. may interfere with the immune destruction of intracellular tubercle bacilli and that the mechanisms of immunity against mycobacteria and leishmania may differ.