Human immunodeficiency virus type 1 infection of alveolar macrophages impairs their innate fungicidal activity

Impaired adaptive immunity is the hallmark of AIDS, but the effects of huma n immunodeficiency virus type 1 (HIV-1) infection on innate immunity are le ss clear. Cryptococcus neoformans (CN) is a common AIDS-related fungal path ogen acquired by inhalation. Alveolar macrophages (AM phi) comprise the ini tial host defense in cryptococcosis and they may arrest infection before di ssemination occurs. We hypothesized that HIV-1 infection of AM phi impairs their anti-cryptococcal activity. This was tested by infection of normal AM phi with the M-tropic strain HIV-1(Bal). Two weeks postinfection we measur ed fungistatic activity against CN by colony counting, binding, and interna lization of CN by confocal microscopy and AM phi cell viability by Alamar B lue assay. Uninfected AM phi from most donors demonstrated innate fungicida l activity against CN. In HIV-1-infected AM phi, there was a significant re duction, and in most cases loss, of fungicidal activity compared with the u ninfected AM phi. The reduced antifungal activity was not due to any cytoto xic effect of HIV-1, and HIV-1 infection did not impair binding or internal ization of yeast by AM phi. Thus, the innate fungicidal activity of primary human AM phi is impaired after HIV-1 infection in vitro by a mechanism inv olving a defect of intracellular antimicrobial processing.