Recombinant and natural gamma-interferon activation of macrophages in vitro: 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 to kill C. albicans, but not B. dermatitidis, which was shown to be associated with residual (10%) lymphocytes in the monolayers. Lipopolysaccharide (0.001 to 10 micrograms/ml) failed to consistently activate M phi for fungicidal activity. These data show that IFN can exert an immunoregulatory role on M phi defense against these fungal pathogens.
D000818:Animals; D000906:Antibodies / Q000276:immunology; D003208:Concanavalin A / Q000494:pharmacology; D004274:DNA, Recombinant; D004305:Dose-Response Relationship, Drug; D005658:Fungi / Q000276:immunology*; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000187:drug effects*
D000906:Antibodies; D004274:DNA, Recombinant; D008070:Lipopolysaccharides; D003208:Concanavalin A; D007371:Interferon-gamma