Serum-mediated enhancement of TNF-α release by human monocytes stimulated with the yeast form of Candida albicans

Abstract

The role of serum in the production of tumor necrosis factor-α (TNF- α) by human monocytes stimulated with yeast-form Candida albicans was studied. Pre-exposure of C. albicans to human pooled serum enhanced both TNF- α mRNA and cytokine secretion compared with C. albicans preincubated with medium only. Serum factors involved were >30 kDa, were efficiently inhibited by D-mannose, and recognized both Ca++-dependent and -independent pathways. Preincubation of yeasts with rabbit mannose-binding protein (MBP) resulted in dose-related enhancement of TNF-α secretion, through a Ca++-dependent pathway inhibited by D-mannose. TNF-α levels were similarly induced in C. albicans preincubated with vitronectin and with serum. Ca++ depletion did not affect cytokine release, while D-mannose supplementation displayed inhibition. The latter effect was abolished after Ca++ depletion. These data call for an involvement of both MBP and vitronectin in the serum- mediated enhancement of TNF-α release upon stimulation of monocytes with yeast forms of C. albicans.