XI International Meeting on Paracoccidioidomycosis

XI International Meeting on Paracoccidioidomycosis

Resume:134-1

Poster (Painel)

134-1	Human neutrophils treated with IL-17 presented diminished fungicidal activity against P. brasiliensis yeast cells, besides increased expression of adhesion molecules and chemokine receptors.
Authors:	Munir Regini Paiao (UNICAMP - Universidade Estadual de Campinas) ; Maria Heloisa Souza Lima Blotta (UNICAMP - Universidade Estadual de CampinasUNICAMP - Universidade Estadual de Campinas) ; Ronei Luciano Mamoni (UNICAMP - Universidade Estadual de CampinasUNICAMP - Universidade Estadual de CampinasUNICAMP - Universidade Estadual de Campinas)

Abstract

Background and objectives: Paracoccidioidomycosis (PCM) lesions are characterized by inflammatory infiltrates containing numerous neutrophils, however, neutrophils from PCM patients presented diminished fungicidal activity when compared to cells from healthy subjects. Recently, it was showed that IL-17 can participate in immunological responses against fungi, and that this cytokine had an important effect on neutrophils activities. The aim of this study was to evaluate the participation of IL-17 in human PCM, and its role on fungicidal activity and migratory capability of PMNs. Methods and results: We evaluated the production of IL-17 by PBMCs (stimulated with PHA for 24 hours) from healthy controls and PCM patients presenting the Juvenile Form (JF) or the Adult Form (AF) of the disease. The results showed that AF patients produced large amounts of IL17 in comparison to the JF patients and controls. We also, isolated neutrophils from peripheral blood of PCM patients (AF or JF) and controls and evaluated their fungicidal activity against P. brasiliensis (strains: Pb18 and Pb265 – by CFUs counting), as well as the production of MMP-9 (matrix metallo proteinase-9 – by ELISA) and the expression of CXCR1 and CXCR2, IL17RA and IL23R and adhesion molecules (CD54 and CD62L), after the treatment with IL-17 (100ng/mL) and/or IL-23 (100ng/mL) (for 4 and 24 hours) by qRT-PCR and flow cytometry. The results showed that neutrophils stimulated with IL-17 and IL-23 exhibited a decreased antifungal activity, while presented an increased production of MMP-9. Furthermore, neutrophils treated with the cytokines showed an augmented expression of CXCR1, CXCR2, CD54, CD62L, IL17R and IL-23R. Discussion and conclusions: Our results indicate that IL-17 can participate in the inflammatory response observed in PCM patients. Neutrophils exposed to IL17 and IL23 increased their expression of CXCR1, CXCR2, CD54 and CD62L, which can increase their migratory capacity in response to the production of IL-8 (CXCL8) in lesions. Furthermore, the treatment of PMNs with IL-17 and IL-23 had a suppressive effect on fungicidal activity, but increased the production of MMP-9. These results may indicate that neutrophils exposed to Th17 related cytokines may contribute to the inflammatory reaction and tissue destruction, while will present poorly fungicidal activity.

Keyword: adhesion molecules, chemokine receptors, immune response, IL-17, Paracoccidioidomycosis

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