Recombinant and Natural Gamma-Interferon Activation of Macrophages in Vitro: Different Dose Requirements for Induction of Killing Activity against Phagocytizable and Non-Phagocytizable Fungi

摘要

Recombinant murine gamma-interferon (IFN) and supernatants form concanavalin A (ConA)-stimulated spleen cells were tested for their ability to activate resident peritoneal macrophages (MPhi) for fungicidal activity. MPhi monolayers pulsed overnight with IFN exhibited significantly enhanced fungicidal activity against Canadida albicans (44 + or - 12 versus 0.0% ) and Blastomyces dermatitidis (34 + or - 1 versus 3 + or - 3%). The effect of IFN was dose dependent; however, less IFN (10 U/ml) was required to activate MPhi 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 MPhi 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 MPhi for fungicidal activity. These data show that IFN can exert an immunoregulatory role on MPhi defense against these fungal pathogens.