THE TIMING OF EXPOSURE OF MONONUCLEAR PHAGOCYTES TO RECOMBINANT INTERFERON GAMMA AND RECOMBINANT TUMOR-NECROSIS-FACTOR-ALPHA ALTERS INTERACTIONS WITH NOCARDIA-ASTEROIDES

Nocardia asteroides modulates phagocyte function and grows within macrophages. Because interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) have been shown to activate macrophages to kill a variety of microorganisms, the effects of IFN-gamma and TNF-alpha on the activation of murine macrophages and human monocytes to kill nocardiae were studied. It was found that macrophages or monocytes treated with either IFN-gamma, TNF-alpha, or lipopolysaccharide as a secondary signal did not demonstrate increased microbicidal activity against N. asteroides even though these phagocytes were effective at killing the fungus Coccidioides immitis and the protozoan Toxoplasma gondii. Preincubation of phagocytes for 24 h with these compounds resulted in an enhancement of nocardial growth. In contrast, coincubation of these factors with the nocardiae and mononuclear cells during phagocytosis resulted in inhibition of nocardial growth even though this bacterium was not killed. Therefore, the specific timing of the exposure of the phagocyte in vitro to IFN-gamma or TNF-alpha has a significant effect on its ability to alter nocardial growth.