Eicosanóides role on Paracoccidioidomycosis

Abstract

Prostaglandins and leukotrienes are eicosanoides playing an important role on modulation of immune response in several infections. Studies in our laboratory have been evaluated the role of these eicosanoides on paracoccidioidomycosis. The results showed that P.brasiliensis induces human monocytes to produce prostaglandins that inhibit fungicidal activity by these cells. Prostaglandins action mechanism involved TNF-a inhibition with consequent reduction on H2O2 levels ,the metabolite involved in P.brasiliensis killing by human monocytes. By other hand, preliminary studies on our laboratory showed that P.brasiliensis induces leukotrienes production, that different from prostaglandins, increase fungus killing by human monocytes. These studies clearly demonstrated that P.brasiliensis induces human cells to produce eicosanoides that modulate cells antifungal functions. However, other studies on our laboratory have been shown that P.brasiliensis itself produces both prostaglandins and leukotrienes, using endogenous and exogenous arachidonic acid source. Moreover, the studies showed that these eicosanoids are involved in fungal survival. This process is reported for other fungi, and is suggested to be associated to a virulence mechanism, with important implications for pathogenesis of fungal infections. In this context, we assessed to advance in our studies on caracterization and biological activities of P,brasiliensis eicosanoides. Our objectives are: 1- to evaluate the capacity of different P.brasiliensis strains to produce different metabolites resulting from arachidonic acid biosynthesis. 2- to characterize and purify prostaglandins and leukotrienes produced by the different strains. 3- to evaluate the presence of genes codifying the enzymes cyclooxygenase and lipoxygenase, or other enzymes with functional homology. 4 To study the role of purified prostaglandins and leukotrienes on human phagocytic cell functions. (AU)