Fungicidal activity of human dendritic cells against P. brasiliensis: role of oxygen metabolites, cytokines and pattern recognizing receptors

Abstract

Paracoccidioidomycosis is a systemic mycosis whose etiological agent is the dimorphic fungus Paracoccidioides brasiliensis. Phagocytic cells play an important role on the immune response against this fungus, actuating as both, effector cells in fungicidal and fungistatic activities and as modulators of the inflammatory response resulting from their interaction with the fungus. Regarding effector functions studies have shown that human neutrophils, monocytes and murine macrophages exert fungicidal activity against P.brasiliensis after activation with the cytokines IFN-g, TNF-±, GM-CSF e IL-15. This activity is mediated by products from oxidative metabolism, mainly H2O2. Dendritic cells are essential for early microrganisms recognizing as well as for instructing adaptative immune response. This second aspect has been studied in paracoccidioidomycosis. However, similarly to neutrophils, monocytes and macrophages, these cells could also play an important role as effector cells. Differences in the capacity of DCs to kill P.brasiliensis, may result in differences in the dissemination of the fungus during their migration from periphery to secundary lymphoid organs. In this context, the main objective of this study is to evaluate whether human DCs exert fungicidal activity against P.brasiliensis and the involvement of NADPoxidase system activation in this process. Moreover, the participation of different pattern recognizing receptors ( PRRS) and activators cytokines such as IFN-g e TNF-a will be evaluated. (AU)