Modulatory effect of prostaglandins on human monocyte activation for killing of high‐ and low‐virulence strains of Paracoccidioides brasiliensis

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Abstract
The effect of indomethacin (Indo), a cyclo-oxygenase inhibitor, on the monocyte-mediated killing of a low- (Pb265) and a high- (Pb18) virulence strain of Paracoccidioides brasiliensis was examined. The Pb18 strain was not killed by either non-activated or interferon-γ (IFN-γ) -activated human monocytes but these cells did show fungicidal activity if pretreated with Indo. In contrast with IFN-γ, tumour necrosis factor-α (TNF-α) was very effective at stimulating the fungicidal activity of monocytes. While the low-virulence strain, Pb265, could not be killed by monocytes, cells preincubated with IFN-γ demonstrated fungicidal activity. The killing of this strain was also induced by pretreatment of monocytes with Indo. The results suggest a negative role for prostaglandins, which are synthesized via the cyclo-oxygenase pathway, in the regulation of monocyte-mediated killing of virulent and avirulent strains of P. brasiliensis and that TNF-α generation during the fungus–monocyte interaction is more important in the killing of Pb265 than Pb18.