XI International Meeting on Paracoccidioidomycosis

XI International Meeting on Paracoccidioidomycosis

Resume:75-1

Poster (Painel)

75-1	Antifungal activity of human monocytes against a new isolate of Paracoccidioides brasiliensis਀
Authors:	Daniela Ramos Rodrigues (UNESP - Universidade Estadual Paulista) ; Ana Paula Bordon-graciani (UNESP - Universidade Estadual Paulista) ; Cibele Ferrari (UNESP - Universidade Estadual Paulista) ; Gil Benard (USP - Universidade de São Paulo) ; Ângela Maria Victoriano de Campos Soares (UNESP - Universidade Estadual Paulista)

Abstract

Introduction: Paracoccidiodomycosis (Pbmycosis) is a systemic mycosis caused by P. brasiliensis (Pb), which is endemic in Latin America. The host innate immune response against the fungus has been well characterized and several studies have clearly shown the important role played by phagocytic cells. Our laboratory has studied the relationship between human monocytes/ Pb strains with different virulences. The results have clearly shown that capacity of monocytes to kill the fungus is highly dependent on activation by cytokines and strain virulence. In this context, some cytokines such as TNF-alpha and GM-CSF are more effective than IFN-gamma in inducing high H2O2 levels and consequently effective fungicidal activity. In addition, higher H2O2 levels are released by low virulent Pb strains in relation to high virulent ones. Recently, a one and half year-old child, with no obvious history of exposition to P.brasiliensis, was diagnosed with severe, disseminated Pbmycosis. This is probably the youngest case of Pbmycosis that was reported. Some studies have been performed to better understand the characteristics of the isolate obtained from this patient. Objectives: We compared antifungal functions of monocytes against this isolate with those detected for classical strains used in our laboratory (Pb 18 and Pb 265). Methodology: Peripheral blood monocytes obtained from 10 healthy donors were activated or not with IFN-gamma, TNF-alpha or GM-CSF for 18h, and further challenged with Pb18, Pb265 and the child isolate (called PbAB), for 4h. After, cultures were evaluated for fungicidal activity, H2O2 release and TNF-alpha and IL-10 production by ELISA. Results: As expected, H2O2 production and killing activity were more effective after TNF-alpha and GM-CSF activation for all strains tested. However, of note, was the observation that after challenge with PbAB the fungicidal activity was lower than that detected with Pb265 and even with Pb18, respectively the low and high virulence reference strains. Furthermore, PbAB induces low levels of TNF-alpha but increases the production of IL-10 when compared with strains Pb18 and Pb265. Conclusion: These results reinforce the idea that higher virulence of some strains of P. brasiliensis is associated, at least partially, with their greater ability to escape from the effector mechanisms of phagocytic cells and thus induce a more severe disease.

Keyword: Antifungal activity, cytokines, human monocytes, Paracoccidioides brasiliensis

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