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

The role of serum in the production of tumor necrosis factor-alpha (TNF-alp ha) by human monocytes stimulated with yeast-form Candida albicans was stud ied. Pre-exposure of C. albicans to human pooled serum enhanced both TNF-al pha mRNA and cytokine secretion compared with C, albicans preincubated with medium only. Serum factors involved were >30 kDa, were efficiently inhibit ed by D-mannose, and recognized both Ca++-dependent and -independent pathwa ys, Preincubation of yeasts with rabbit mannose-binding protein (MBP) resul ted in dose-related enhancement of TNF-alpha secretion, through a Ca++-depe ndent pathway inhibited by D-mannose, TNF-alpha levels were similarly induc ed in C. albicans preincubated with vitronectin and with serum. Ca++ deplet ion did not affect cytokine release, while D-mannose supplementation displa yed inhibition. The latter effect was abolished after Ca++ depletion. These data call for an involvement of both MBP and vitronectin in the serum-medi ated enhancement of TNF-alpha release upon stimulation of monocytes with ye ast forms of C. albicans.