Killing of Histoplasma capsulatum by gamma-interferon-activated human monocyte-derived macrophages: evidence for a superoxide anion-dependent mechanism

Abstract

The interaction of human macrophages with the yeast form of the thermally dimorphic fungal pathogen, Histoplasma capsulatum, was studied. Macrophages derived from monocytes by culture in vitro for 3 days ingested H. capsulatum, but were neither fungicidal or fungistatic. In contrast, when monocytes were exposed to human recombinant gamma-interferon (gamma-IFN) during their differentiation into macrophages, those macrophages were able to reduce the number of ingested or adherent cfu of H. capsulatum by 44-75% in 2 h. Activation of macrophages for fungicidal activity by gamma-IFN was dose dependent and 500-1000 units ml were optimal. Antibody to gamma-IFN abrogated the gamma-IFN activation process. Killing of H. capsulatum by activated macrophages in 2-h assays could be inhibited by superoxide dismutase but not by sodium azide.