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Glucosylceramides from Lomentospora prolificans induce a differential production of cytokines and increases the microbicidal activity of macrophages
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Autores
da Silva Xisto, Mariana Ingrid Dutra
Muñoz Henao, Julián Esteban
dos Santos Dias, Lucas
Santos, Giulia Maria Pires
de Oliveira Rocha Calixto, Renata
Bernardino, Mariana Collodetti
Taborda, Carlos Pelleschi
Barreto-Bergter, Eliana
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Fecha
2019
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Frontiers Media S.A.
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Resumen
Abstract
Lomentospora prolificans is an emerging opportunistic fungus with a high resistance to antifungal agents and it can cause localized infections in immunocompetent patients and disseminated infections with a high mortality rate in immunosuppressed patients. Glucosylceramides (GlcCer) are synthetized in the majority of known fungal pathogens. They are bioactive molecules presenting different functions, such as involvement in fungal growth and morphological transitions in several fungi. The elucidation of the primary structure of the fungal surface glycoconjugates could contribute for the understanding of the mechanisms of pathogenicity. In this work, GlcCer species were isolated from mycelium and conidia forms of L. prolificans and their chemical structures were elucidated by mass spectrometry (ESI-MS). GlcCer purified from both forms presented a major species at m/z 750 that corresponds to N-2-hydroxyhexadecanoyl-1-?-D-glucopyranosyl-9-methyl-4,8-sphingadienine. Monoclonal antibodies against GlcCer could recognize L. prolificans GlcCer species from mycelium and conidia, suggesting a conserved epitope in fungal GlcCer. In addition, in vivo assays showed that purified GlcCer species from both forms was able to induce a high secretion of pro-inflammatory cytokines by splenocytes. GlcCer species also promote the recruitment of polymorphonuclear, eosinophils, small peritoneal macrophage (SPM) and mononuclear cells to the peritoneal cavity. GlcCer species were also able to induce the oxidative burst by peritoneal macrophages with NO and superoxide radicals production, and to increase the killing of L. prolificans conidia by peritoneal macrophages. These results indicate that GlcCer species from L. prolificans are a potent immune response activator. Copyright © 2019 Xisto, Henao, Dias, Santos, Calixto, Bernardino, Taborda and Barreto-Bergter.
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Keywords
CXCL2 chemokine , Gamma interferon , Glucosylceramide , Interleukin 10 , Interleukin 17 , Superoxide , Tumor necrosis factor , Animal experiment , Animal model , Antigen recognition , Antioxidant activity , Article , Carbohydrate analysis , Cellular distribution , Cytokine production , Electrospray mass spectrometry , Enzyme linked immunosorbent assay , Female , Fungus growth , High performance thin layer chromatography , Immune response , Immunocompetence , Immunocompromised patient , Immunodetection , Immunofluorescence , Immunohistochemistry , Immunoreactivity , Macrophage , Microbicidal activity , Mortality rate , Mouse , Nonhuman , Pathogenicity , Phagocytosis , Respiratory burst , Glccer , Glucosylceramides , Innate immune response , Lomentospora prolificans , Structural characterization
