Glucosylceramides From Lomentospora prolificans Induce a Differential Production of Cytokines and Increases the Microbicidal Activity of Macrophages

Autor(es)

Dutra da Silva Xisto, Mariana Ingrid ^[1] ; Munoz Henao, Julian Esteban ^[2] ; Dias, Lucas dos Santos ^{[3, 4, 5]} ; Pires Santos, Giulia Maria ^[6] ; Rocha Calixtol, Renata de Oliveira ^[1] ; Bernardino, Mariana Collodetti ^[1] ; Taborda, Carlos Pelleschi ^{[3, 4]} ; Barreto-Bergter, Eliana ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Rio de Janeiro, Ctr Ciencias Saude, Inst Microbiol Paulo Goes, Lab Quim Biol Microrganismos, Dept Microbiol Geral, Rio De Janeiro - Brazil

^[2] Univ Rosario, Sch Med & Hlth Sci, Studies Translat Microbiol & Emerging Dis Res Grp, Bogota - Colombia

^[3] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Med Mycol Lab, Med Sch, Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Med Mycol Lab, Trop Med Inst, Sao Paulo, SP - Brazil

^[5] Univ Wisconsin, Dept Pediat, Sch Med & Publ Hlth, Madison, WI - USA

^[6] Univ Fed Fluminense, Dept Microbiol & Parasitol, Inst Biomed, Niteroi, RJ - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN MICROBIOLOGY; v. 10, MAR 22 2019.
• Citações Web of Science: 1

Resumo

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). GIcCer purified from both forms presented a major species at m/z 750 that corresponds to N-2-hydroxyhexadecanoyl-1-beta-D-glucopyranosyl-9-methyl-4,8-sphingadien ine. Monoclonal antibodies against GlcCer could recognize L. prolificans GIcCer 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. (AU)

• Processo FAPESP: 16/08730-6 - Patogenicidade fúngica: efeito do tabagismo, resposta imune e a modulação vacinal na paracoccidioidomicose e na histoplasmose
• Beneficiário: Carlos Pelleschi Taborda
• Linha de fomento: Auxílio à Pesquisa - Temático