XI International Meeting on Paracoccidioidomycosis

XI International Meeting on Paracoccidioidomycosis

Resume:154-1

Investigação

154-1	The role of NK cells in human Paracoccidioidomycosis
Authors:	Ronei Luciano Mamoni (UNICAMP - Universidade Estadual de Campinas)

Abstract

Besides their role in viral infection and tumor resistance, recent studies have showed that NK cells also participate in the immune response against other infectious diseases. The aim of this study was to evaluate the possible role for NK cells (CD56+ cells) in the immune response against the dimorphic fungus Paracoccidioides brasiliensis. It was found that NK cells from patients present a lower citotoxic response when compared to healthy individuals. The analyses of CD56+ cells from controls showed an elevated expression of CD25 and CD69 after the stimulus with yeast cells, while cells from patients are activated only in the presence of IL-15. Furthermore, our results showed that CD56+ cells are able to directly recognize and kill P. brasiliensis yeast cells, and that this activity seems to be granule-dependent but perforin-independent, while the citotoxicity against monocytes infected with P. brasiliensis showed to be perforin-dependent. Infected monocytes augmented their expression for IL-15 mRNA, while exhibit a diminished number of MHC class I molecules, associated with an increased expression of MICA/B molecules in their surface. It was also observed an augmented expression of granulysin in NK cells from healthy individuals, and that CD56+ cells are able to produce and release granulysin after stimulation with P.brasiliensis. One possible mechanism for the recognition of P. brasiliensis by NK cells is through the TLR2, TLR4 and CR3. We observed that NK cells express TLR2 and CR3 on their surface, and that IL-15 increases the expression of TLR2. These results demonstrated that CD56+ cells can actively participate in the immune response against the P. brasiliensis infection either by directly destroying yeast cells or by the recognition and killing of infected cells. Granulysin is the possible mediator of the cytotoxic effect observed in this study, once this protein is produced and released by CD56+ cells. Furthermore, our data showed that NK cells express TLR2, TLR4 and CR3, which may be responsible for the recognition of yeast cells through the beta-glucan present in the yeasts cell-walls. Another important data is the finding that CD56+ cells are able to produce IFN-gamma and TNF-alpha, which could influence the subsequent acquired immunological response by stimulating other cells as dendritic cells, macrophages and lymphocytes.

Keyword: Granulysin, NK cells, TLR2, Paracoccidioidomycosis

਀�