Paracoccidioides brasiliensis INHIBITS H2O2 RELEASE  BY HUMAN NEUTROPHILS

ACORCI M. J.(1), BORDON A. P.(1), DIAS-MELICIO L. A.(1), CALVI S. A.(1), PERAÇOLI M. T. S.(1), SOARES A. M. V. C.(1)

(1)Department of Microbiology and Immunology, Biosciences Institute, UNESP Botucatu, SP, Brazil;

Polymorphonuclear neutrophils (PMNs) are the predominant cells present in the early phases of murine infection with P. brasiliensis. In humans, the early histopathologic characteristics of paracoccidioidomycosis are not fully understood, but there are strong evidences that PMNs are involved in the primary host response to fungus, since studies point out the presence of these cells in infected tissues. Despite of these observations, the mechanisms involved in the response of human PMNs to fungus challenge are poorly studied. Previous studies have been demonstrated that human PMNs fail to kill P. brasiliensis. Since, P. brasiliensis killing by human phagocytes is dependent on oxygen metabolites, the objective of this paper is to assess if the inability of human PMNs to kill P. brasiliensis is related to its capacity to evade oxidative metabolism. Peripheral blood PMNs (2X106/ml) obtained from 10 healthy donors were incubated with tissue culture medium alone, LPS, IFN-g or IL-15 for 18 h, and evaluated for H2O2 release, before and after challenge with high (Pb18) virulent strain of P. brasiliensis (2X104 yeasts/mL) by 4h. P. brasiliensis yeast cells inhibits H2O2 release by unprimed PMNs. However, after PMNs priming with LPS, IFN-g or IL-15 a significative H2O2 release in response to fungus was detected. The results suggest that P. brasiliensis evade oxidative metabolism, by inhibiting H2O2 release and that priming signals by cytokines is necessary to overcome this inhibition.

KEY WORDS: P. brasiliensis, H2O2, PMNs.

CORRESPONDENCE TO:

Michele Janegitz Acorci, Departamento de Microbiologia e Imunologia do Instituto de Biociências, UNESP, Distrito de Rubião Júnior s/n, Botucatu, São Paulo. Caixa Postal: 510; CEP: 18600-000. Email: mjanegitz@hotmail.com