TNF- alpha activates human monocytes for Paracoccidioides brasiliensis killing by an H sub(2)O sub(2)-dependent mechanism

Human monocytes activated by recombinant tumor necrosis factor alpha (TNF- alpha ) exhibited significant fungicidal activity on the yeast cells of a highly virulent strain of Paracoccidioides brasiliensis. This process was significantly inhibited in the presence of catalase (CAT -- a scavenger of H sub(2)O sub(2)), but not in the presence of superoxide-dismutase (SOD -- a scavenger of superoxide anion) or N super(G)-monomethyl-L-arginine (N super(G)-MMLA -- a nitric oxide inhibitor). Furthermore, there was a direct association between the intracellular killing of the fungus and the production of H sub(2)O sub(2) by activated cells. These results strongly suggest a role for H sub(2)O sub(2) in the killing of highly virulent strains of P. brasiiiensis by TNF- alpha -activated human monocytes.