Role of Paracoccidioides brasiliensis cell wall fraction containing beta - glucan in tumor necrosis factor-alpha production by human monocytes: correlation with fungicidal activity

The polysaccharide fraction of Paracoccidioides brasiliensis mycelial cell wall (F1 fraction), the active component of which is composed of beta -glucan, was investigated in regard to the activation of human monocytes for fungal killing. The cells were primed with interferon- (IFN-) or F1 (100 and 200 [mu]g ml-1) or F1 (100 and 200 [mu]g ml-1) plus IFN- for 24 h and then evaluated for H sub(2)O sub(2) release. In other experiments, the cells were pretreated with the same stimuli, challenged with a virulent strain of P. brasiliensis and evaluated for fungicidal activity and levels of tumor necrosis factor (TNF- alpha ) in the supernatants. F1 increased the levels of H sub(2)O sub(2) in a similar manner to IFN-. However, a synergistic effect between these two activators was not detected. On the contrary, a significant fungicidal activity was only obtained after priming with IFN- plus F1. This higher activity was associated with high levels of TNF- alpha in the supernatants of the cocultures. Overall, P. brasiliensis F1 fraction induced human monocytes to release relatively high levels of TNF- alpha , which, in combination with IFN-, is responsible for the activation of human monocytes for effective killing of P. brasiliensis.