Structure, cellular distribution, antigenicity, and biological functions of Fonsecaea pedrosoi ceramide monohexosides.
Monohexosylceramides (CMHs, or cerebrosides) have been reported as membrane and cell wall constituents of both pathogenic and nonpathogenic fungi, presenting remarkable differences in their ceramide moiety compared to mammalian CMHs. Current evidence suggests that CMHs are involved in fungal differentiation and growth and contribute to host immune response. Here we describe a structural diversity between cerebrosides obtained from different forms of the human pathogen Fonsecaea pedrosoi. The major CMH species produced by conidial forms displayed the same structure previously demonstrated by our group for mycelia, an N-2'-hydroxyhexadecanoyl-1-beta-d-glucopyranosyl-9-methyl-4,8-sphingadienine. However, the major cerebroside species purified from sclerotic cells carries an additional hydroxyl group, bound to its long-chain base. The structural difference between cerebrosides from mycelial and sclerotic cells was apparently not relevant for their antigenicity, since they were both recognized at similar levels by sera from individuals with chromoblastomycosis and a monoclonal antibody to a conserved cerebroside structure. Preincubation of fungal cells with anti-CMH monoclonal antibodies had no effect on the interaction of F. pedrosoi sclerotic cells with murine macrophages. In contrast to what has been described for other fungal species, sclerotic bodies are resistant to the antifungal action of anti-CMH antibodies. Immunofluorescence analysis showed that recognition of sclerotic cells by these antibodies only occurs at cell wall regions in which melanization is not evident. Accordingly, melanin removal with alkali results in an increased reaction of fungal cells with anti-CMH antibodies. Our results indicate that cerebroside expression in F. pedrosoi cells is associated with dimorphism and melanin assembly on the fungal cell wall.
Nimrichter
Leonardo
L
Instituto de Microbiologia Professor Paulo de Góes, Departamento de Microbiologia Geral, Universidade Federal do Rio de Janeiro Cidade Universitária, Rio de Janeiro, RJ, 21941-590, Brazil. nimrichter@micro.ufrj.br
Cerqueira
Mariana D
MD
Leitão
Eduardo A
EA
Miranda
Kildare
K
Nakayasu
Ernesto S
ES
Almeida
Sandro R
SR
Almeida
Igor C
IC
Alviano
Celuta S
CS
Barreto-Bergter
Eliana
E
Rodrigues
Marcio L
ML
D000818:Animals; D000908:Antibodies, Fungal / Q000276:immunology; D000946:Antigens, Fungal / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D001203:Ascomycota / Q000276:immunology* / Q000378:metabolism; D002554:Cerebrosides / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D008264:Macrophages / Q000276:immunology; D008543:Melanins / Q000378:metabolism; D051379:Mice
D000908:Antibodies, Fungal; D000946:Antigens, Fungal; D002554:Cerebrosides; D008055:Lipids; D008543:Melanins; C013870:ceramide monohexoside