Killing of Paracoccidioides brasiliensis yeast cells by IFN-[gamma] and TNF-[alpha] activated murine peritoneal macrophages: evidence of H2O2 and NO effector mechanisms

• Published in: Mycopathologia (1975) Vol. 166; no. 1; p. 17
• Main Authors: Moreira, Ana Paula, Dias-melicio, Luciane Alarcão, Peraçoli, Maria Terezinha; S, Calvi, Sueli A, Victoriano De Campos Soares, Angela Maria
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Nature B.V 01-07-2008
• ISSN: 0301-486X; 1573-0832
• DOI: 10.1007/s11046-007-9046-3

Paracoccidioidomycosis is a deep mycosis, endemic in Latin America, caused by Paracoccidioides brasiliensis. Macrophage activation by cytokines is the major effector mechanism against this fungus. This work aimed at a better understanding of the interaction between yeast cells-murine peritoneal macrophages and the cytokine signals required for the effective killing of high virulence yeast-form of P. brasiliensis. In addition, the killing effector mechanisms dependent on the generation of reactive oxygen or nitrogen intermediates were investigated. Cell preincubation with IFN-γ or TNF-α, at adequate doses, resulted in effective yeast killing as demonstrated in short-term (4-h) assays. Both, IFN-γ and TNF-α activation were associated with higher levels of H2O2 and NO when compared to nonactivation. Treatment with catalase (CAT), a H2O2 scavenger, and N(G)-monomethyl-l-arginine (l-NMMA), a nitric oxide synthase inhibitor, reverted the killing effect of activated cells. Taken together, these results suggest that both oxygen and l-arginine--nitric oxide pathways play a role in the killing of highly virulent P. brasiliensis. [PUBLICATION ABSTRACT]