ROLE OF PHAGOCYTIC CELLS IN PARACOCCIDIOIDOMYCOSIS

SOARES, A. M. V. C.(1)

(1)Departamento de Microbiologia e Imunologia, Instituto de Biociências de Botucatu, UNESP

Paracoccidioidomycosis is a deep mycosis caused by Paracoccidioides brasiliensis. Phagocytic cells play a critical role against this fungus with several papers showing macrophages and monocytes antifungal effects. However, despite neutrophils represent the first cells to migrate toward inflamed tissue, works focusing their antifungal functions are scarcer. These findings stimulated us to contribute for the better understanding of human neutrophils role in early infection stages, by studying their capacity to kill P brasiliensis. Nonactivated cells failed to exhibit antifungal activity. However, if they were IFN-g, TNF-a or GM-CSF-activated, a significative fungicidal activity was detected. Killing process was inhibited in presence of catalase and superoxide dismutase showing the role of H2O2 and superoxide anion as effector molecules. Our results indicated that an activation process is essential for neutrophil antifungal activity. Therefore, we asked if IL-10, a suppressor cytokine, would have the capacity to deactivate these cells. This cytokine significantly inhibited P. brasiliensis killing by IFN-g-activated neutrophils, reducing their capacity to release H2O2. The results showed the importance of early neutrophils exposure to activator or suppressor cytokines, for P. brasiliensis killing modulation. However, one question arises in relation to the cellular source of these cytokines in first stages of infection. It has been proposed that NK cells might be the potential source of IFN-g and GM-CSF. TNF-a and IL-10 production might occur by macrophages or even neutrophils. Works in our laboratory have been demonstrated that patient’s monocytes produce high levels of TNF-a and IL-10. These cells also release these cytokines after challenge with fungus in vitro.  These findings suggest that in vivo the potential sources for TNF-a and IL-10 might be alveolar macrophages activated with P. brasiliensis antigens.

CORRESPONDENCE TO:

Ângela Maria Victoriano de Campos Soares, Departamento de Microbiologia e Imunologia, IBB, UNESP. Distrito de Rubião Junior s/nº, 18618-000, Botucatu, SP, Brasil, Caixa Postal: 510, E-mail: acsoares@ibb.unesp.br