title: Modulatory effect of prostaglandins on human monocyte activation for killing of high- and low-virulence strains of Paracoccidioides brasiliensis.
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-gamma (IFN-gamma) -activated human monocytes but these cells did show fungicidal activity if pretreated with Indo. In contrast with IFN-gamma, tumour necrosis factor-alpha (TNF-alpha) 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-gamma 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-alpha generation during the fungus-monocyte interaction is more important in the killing of Pb265 than Pb18.
authors.affiliation: Department of Microbiology and Immunology, Biosciences Institute, and Department of Tropical Diseases, Medical School, UNESP, Botucatu, S.P., Brazil.
authors.forename: A M
authors.initials: AM
authors.lastname: Soares
authors.forename: S A
authors.initials: SA
authors.lastname: Calvi
authors.forename: M T
authors.initials: MT
authors.lastname: Peraçoli
authors.forename: A C
authors.initials: AC
authors.lastname: Fernandez
authors.forename: L A
authors.initials: LA
authors.lastname: Dias
authors.forename: A R
authors.initials: AR
authors.lastname: Dos Anjos
mesh_terms: D000328:Adult; D018929:Cell Culture Techniques; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology; D009000:Monocytes / Q000187:drug effects; D016260:Monocytes, Activated Killer / Q000276:immunology*; D010228:Paracoccidioides / Q000472:pathogenicity; D010229:Paracoccidioidomycosis / Q000276:immunology*; D011453:Prostaglandins / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014774:Virulence
chemical_list: D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D007213:Indomethacin