TY - JOUR
T1 - Compositional and immunobiological analyses of extracellular vesicles released by Candida albicans
AU - Vargas, Gabriele
AU - Rocha, Juliana D.B.
AU - Oliveira, Debora Leite
AU - Albuquerque, Priscila Costa
AU - Frases, Susana
AU - Santos, Suelen S.
AU - Nosanchuk, Joshua Daniel
AU - Gomes, Andre Marco Oliveira
AU - Medeiros, Lia C.A.S.
AU - Miranda, Kildare
AU - Sobreira, Tiago J.P.
AU - Nakayasu, Ernesto S.
AU - Arigi, Emma A.
AU - Casadevall, Arturo
AU - Guimaraes, Allan J.
AU - Rodrigues, Marcio L.
AU - Freire-de-Lima, Celio Geraldo
AU - Almeida, Igor C.
AU - Nimrichter, Leonardo
N1 - Publisher Copyright:
© 2014 John Wiley & Sons Ltd.
PY - 2015/3/1
Y1 - 2015/3/1
N2 - Summary: The release of extracellular vesicles (EV) by fungal organisms is considered an alternative transport mechanism to trans-cell wall passage of macromolecules. Previous studies have revealed the presence of EV in culture supernatants from fungal pathogens, such as Cryptococcus neoformans, Histoplasma capsulatum, Paracoccidioides brasiliensis, Sporothrix schenckii, Malassezia sympodialis and Candida albicans. Here we investigated the size, composition, kinetics of internalization by bone marrow-derived murine macrophages (MO) and dendritic cells (DC), and the immunomodulatory activity of C.albicansEV. We also evaluated the impact of EV on fungal virulence using the Galleria mellonella larvae model. By transmission electron microscopy and dynamic light scattering, we identified two populations ranging from 50 to 100 nm and 350 to 850nm. Two predominant seroreactive proteins (27kDa and 37kDa) and a group of polydispersed mannoproteins were observed in EV by immunoblotting analysis. Proteomic analysis of C.albicansEV revealed proteins related to pathogenesis, cell organization, carbohydrate and lipid metabolism, response to stress, and several other functions. The major lipids detected by thin-layer chromatography were ergosterol, lanosterol and glucosylceramide. Short exposure of MO to EV resulted in internalization of these vesicles and production of nitric oxide, interleukin (IL)-12, transforming growth factor-beta (TGF-β) and IL-10. Similarly, EV-treated DC produced IL-12p40, IL-10 and tumour necrosis factor-alpha. In addition, EV treatment induced the up-regulation of CD86 and major histocompatibility complex class-II (MHC-II). Inoculation of G.mellonella larvae with EV followed by challenge with C.albicans reduced the number of recovered viable yeasts in comparison with infected larvae control. Taken together, our results demonstrate that C.albicansEV were immunologically active and could potentially interfere with the host responses in the setting of invasive candidiasis.
AB - Summary: The release of extracellular vesicles (EV) by fungal organisms is considered an alternative transport mechanism to trans-cell wall passage of macromolecules. Previous studies have revealed the presence of EV in culture supernatants from fungal pathogens, such as Cryptococcus neoformans, Histoplasma capsulatum, Paracoccidioides brasiliensis, Sporothrix schenckii, Malassezia sympodialis and Candida albicans. Here we investigated the size, composition, kinetics of internalization by bone marrow-derived murine macrophages (MO) and dendritic cells (DC), and the immunomodulatory activity of C.albicansEV. We also evaluated the impact of EV on fungal virulence using the Galleria mellonella larvae model. By transmission electron microscopy and dynamic light scattering, we identified two populations ranging from 50 to 100 nm and 350 to 850nm. Two predominant seroreactive proteins (27kDa and 37kDa) and a group of polydispersed mannoproteins were observed in EV by immunoblotting analysis. Proteomic analysis of C.albicansEV revealed proteins related to pathogenesis, cell organization, carbohydrate and lipid metabolism, response to stress, and several other functions. The major lipids detected by thin-layer chromatography were ergosterol, lanosterol and glucosylceramide. Short exposure of MO to EV resulted in internalization of these vesicles and production of nitric oxide, interleukin (IL)-12, transforming growth factor-beta (TGF-β) and IL-10. Similarly, EV-treated DC produced IL-12p40, IL-10 and tumour necrosis factor-alpha. In addition, EV treatment induced the up-regulation of CD86 and major histocompatibility complex class-II (MHC-II). Inoculation of G.mellonella larvae with EV followed by challenge with C.albicans reduced the number of recovered viable yeasts in comparison with infected larvae control. Taken together, our results demonstrate that C.albicansEV were immunologically active and could potentially interfere with the host responses in the setting of invasive candidiasis.
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U2 - 10.1111/cmi.12374
DO - 10.1111/cmi.12374
M3 - Article
C2 - 25287304
AN - SCOPUS:84925052199
SN - 1462-5814
VL - 17
SP - 389
EP - 407
JO - Cellular Microbiology
JF - Cellular Microbiology
IS - 3
ER -