title: A monoclonal antibody to glucosylceramide inhibits the growth of Fonsecaea pedrosoi and enhances the antifungal action of mouse macrophages.
abstract: Fungal glucosylceramides (GlcCer) are conserved lipid components in a large variety of pathogenic and non-pathogenic fungal species, but their biological functions are still unclear. Recent studies demonstrate that GlcCer are immunologically active components inducing the production of antifungal antibodies. In this work, a major GlcCer was purified and characterized from mycelial forms of Fonsecaea pedrosoi, the most frequent causative agent of chromoblastomycosis. As determined by fast atom bombardment mass spectrometry (FAB-MS) analysis, the purified molecule was identified as the conserved structure N-2'-hydroxyhexadecanoyl-1-beta-D-glucopyranosyl-9-methyl-4,8-sphingadienine. A monoclonal antibody (Mab) against this structure was used in indirect immunofluorescence with the different morphological stages of F. pedrosoi. Only the surface of young dividing cells was recognized by the antibody. Treatment of F. pedrosoi conidia with the Mab against GlcCer resulted in a clear reduction in fungal growth. In addition, the Mab also enhanced phagocytosis and killing of F. pedrosoi by murine cells. These results suggest that, in F. pedrosoi, GlcCer seem to be cell wall components targeted by antifungal antibodies that directly inhibit fungal development and also enhance macrophage function, supporting the use of monoclonal antibodies to GlcCer as potential tools in antifungal immunotherapy.
authors.affiliation: Departamento de Microbiologia Geral, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Cidade Universitária, CCS, Bloco I, Ilha do Fundão, 21941-590, Brazil.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Nimrichter
authors.forename: Eliana
authors.initials: E
authors.lastname: Barreto-Bergter
authors.forename: Ricardo R
authors.initials: RR
authors.lastname: Mendonça-Filho
authors.forename: Lucimar F
authors.initials: LF
authors.lastname: Kneipp
authors.forename: Mariana T
authors.initials: MT
authors.lastname: Mazzi
authors.forename: Patrícia
authors.initials: P
authors.lastname: Salve
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Farias
authors.forename: Robin
authors.initials: R
authors.lastname: Wait
authors.forename: Celuta S
authors.initials: CS
authors.lastname: Alviano
authors.forename: Marcio L
authors.initials: ML
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000276:immunology / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D001203:Ascomycota / Q000737:chemistry / Q000187:drug effects* / Q000254:growth & development* / Q000276:immunology; D002862:Chromoblastomycosis / Q000276:immunology / Q000382:microbiology; D005260:Female; D005963:Glucosylceramides / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects*
chemical_list: D000908:Antibodies, Fungal; D000911:Antibodies, Monoclonal; D005963:Glucosylceramides