Defective induction of interleukin-12 in human monocytes by germ-tube forms of Candida albicans

Yeast TY) to germ-tube (GT) transition of Candida albicans is considered a putative virulence trait. On the other hand, interleukin-12 (IL-12) is a key promoter of T-helper type 1 protective immunity against this human opportunistic pathogen, We studied IL-12 production by human monocytes cocultured in vitro with Y or GT forms of C. albicans, Following stimulation by Y cells, monocytes produced appreciable levels of 1L-12, which, upon addition of gamma interferon (IFN-gamma), compared to those achievable by lipopolysaccharide (100 ng/ml) stimulation (140 +/- 65 and 185 +/- 80 pg/ml, respectively [mean +/- standard deviation in four independent experiments]), In contrast, 1L-12 production by GT cell-stimulated monocytes was much lower or absent (<5 pg/ml) and could not be brought to the level induced by Y cells by the addition of IFN-gamma (30 +/- 10 pg/ml in the four independent experiments above). Besides being observed as actual cytokine production, this lower response was also observed as specific IL-12 p40 mRNA transcript and was not associated with hyperprodoction of the IL-12-competing cytokine IL-10, Phagocytosis and killing experiments in the presence of cytochalasin D showed that IL-12 production by Y cell-stimulated monocytes was phagoEytosis dependent and that GT cells of C, albicans were not phagocytized by the human monocytes, Importantly, however, Y and ST cells were equally killed by the monocytes, Thus, the virulence trait attributed to the Y-GT transition of C, albicans might also be related to the lack of induction by GT cells of a protective anticandidal immunity through defective IL-12 production.