TNF-α activates human monocytes for Paracoccidioides brasiliensis killing by an H2O2-dependent mechanism

Human monocytes activated by recombinant tumor necrosis factor alpha (TNF-α) 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 H2O2), but not in the presence of superoxide-dismutase (SOD — a scavenger of superoxide anion) or NG-monomethyl-L-arginine (NG-MMLA — a nitric oxide inhibitor). Furthermore, there was a direct association between the intracellular killing of the fungus and the production of H2O2 by activated cells. These results strongly suggest a role for H2O2 in the killing of highly virulent strains of P. brasiliensis by TNF-α-activated human monocytes.