Am. J. Respir. Cell Mol. Biol., Vol 15, No. 6, 12 1996, 711-715.
Interferon-gamma reduces the capacity of human alveolar macrophages to inhibit growth of Cryptococcus neoformans in vitro
CC Reardon, SJ Kim, RP Wagner and H Kornfeld
Pulmonary Center, Boston University School of Medicine, Massachusetts 02118, USA.
Cytokine stimulation of mouse and rat macrophages has previously been shown
to enhance their capacity to phagocytose and inhibit the growth of
Cryptococcus neoformans. To extend these observations to primary human
macrophages, we investigated the anticryptococcal activity of human
alveolar macrophages stimulated with interferon-gamma (IFN- gamma), tumor
necrosis factor-alpha (TNF-alpha), or macrophage-colony stimulating factor
(M-CSF). Neither TNF-alpha nor M-CSF had any effect on fungal growth
inhibition compared with unstimulated macrophages. Alveolar macrophages
stimulated with IFN-gamma demonstrated reduced fungistasis for C.
neoformans compared with controls (49% +/- 15% versus 75% +/- 12%; mean %
growth inhibition +/- SD, P < 0.001). Confocal laser scanning microscopy
was used to assess binding and phagocytosis of yeast. No difference was
observed between unstimulated macrophages and macrophages stimulated with
any of the cytokines tested. These data suggest that the cytokine
regulation of anticryptococcal macrophage functions in humans differs from
the rat and mouse. Conclusions drawn from these models may not necessarily
be applicable to human cryptococcosis. In particular, the effects of IFN-
gamma on the interaction of human alveolar macrophages with C. neoformans
was not predicted based on the mouse and rat macrophage responses.
