RECOMBINANT AND NATURAL GAMMA-INTERFERON ACTIVATION OF MACROPHAGES INVITRO - DIFFERENT DOSE REQUIREMENTS FOR INDUCTION OF KILLING ACTIVITY AGAINST PHAGOCYTIZABLE AND NONPHAGOCYTIZABLE FUNGI

Recombinant murine gamma-interferon (IFN) and supernatants from concanavalin A (ConA)-stimulated spleen cells were tested for their ability to activate resident peritoneal macrophages (M.PHI.) for fungicidal activity. M.PHI. monolayers pulsed overnight with IFN exhibited significantly enhanced fungicidal activity against Candida albicans (44 .+-. 12 versus 0.0%) and Blastomyces dermatitidis (34 .+-. 1 versus 3 .+-. 3%). The effect of IFN was dose dependent; however, less IFN (10 U/ml) was required to activate M.PHI. to kill phagocytizable C. albicans than to kill nonphagocytizable B. dermatitidis (1,000 U/ml). ConA-stimulated spleen cell supernatants were also able to activate M.PHI. for fungicidal activity against both fungi. The capacity of ConA-stimulated spleen cell supernatants to activate M.PHI. for fungicidal activity was neutralized in the presence of antibody to murine IFN. ConA-treated monolayers acquired the ability of kill C. albicans, but not B. dermatitidis, which was shown to be associated with residual (10%) lymphocytes in the monolayers. Lipopolysaccharide (0.001-10 .mu.g/ml) failed to consistently activate M.PHI. for fungicidal activity. These data show that IFN can exert an immunoregulatory role in M.PHI. defense against these fungal pathogens.