XI International Meeting on Paracoccidioidomycosis

XI International Meeting on Paracoccidioidomycosis

Resume:157-1

Oral / Poster

157-1	A monoclonal antibody to glucosylceramide of Paracoccidiodies brasiliensis enhances the antifungal action of macrophages
Authors:	Luciana Thomaz (USP - University of São Paulo) ; Fernanda Dias da Silva (USP - University of São Paulo) ; Marcia Ribeiro Pinto da Silva (USP - University of São Paulo) ; Paula Cristina Martinelli Barbarian (USP - University of São Paulo) ; Viviana Sarria (USP - University of São Paulo) ; Carlos Pelleschi Taborda (USP - University of São PauloUSP - University of São Paulo)

Abstract

Glycosphingolipidis are amphipathic molecules consisting of a ceramide lipids moiety linked to a glycan chain of variable length and structure. These molecules have been implicated in many fundamental cellular processes, including growth, differentiation, and morphogenesis. The ceramide monohexosides (CMHs) gluco- and galactosylceramides are the main neutral glycosphingolipids expressed in fungal pathogens such as Paracoccidioides brasiliensis. Recently studies showed that glycosphingolipidis are immunologically active components inducing the production of antifungal antibodies. Some of these structures can be specifically recognized by antibodies from patientâ€™s sera with fungal infections, suggesting that they can be useful in the diagnosis and could be target for new therapeutic agents. CMHs are conserved molecules in a large pathogenic fungal species as in P. brasiliensis, thermally dimorphic fungal, etiological agent of paracoccidioidomycosis, the most prevalent systemic mycosis in Latin America that is endemic in areas of Brazil, Argentina, Colombia and Venezuela. In the present study, CMH was purified from P. brasiliensis (Pb18) and a monoclonal antibody (IgM mAb) was produced against this structure, which was used in electron microscope. The cell surface was recognized by IgM mAb against CMH. We also investigated the influence of the IgM mAb in phagocytosis and killing assays of P. brasiliensis. The IgM mAb, in the presence of complement, increased by two fold the potential of macrophages J774.17 and showed strong activity in killing assay. The present work shows that, in P. brasiliensis, CMH seem to be cell components targeted by antifungal antibodies that enhance macrophage function, supporting the use of monoclonal antibodies to CMH as potential tolls in antifungal immunotherapy.

Keyword: Paracoccidioides brasiliensis, glucosylceramide, monoclonal antibody

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