Extracellular vesicles from Cryptococcus neoformans modulate macrophage functions

Débora L. Oliveira, Célio G. Freire-de-Lima, Joshua D. Nosanchuk, Arturo Casadevall, Marcio L. Rodrigues, Leonardo Nimrichter

Research output: Contribution to journalArticle

124 Scopus citations

Abstract

Cryptococcus neoformans and distantly related fungal species release extracellular vesicles that traverse the cell wall and contain a varied assortment of components, some of which have been associated with virulence. Previous studies have suggested that these extracellular vesicles are produced in vitro and during animal infection, but the role of vesicular secretion during the interaction of fungi with host cells remains unknown. In this report, we demonstrate by fluorescence microscopy that mammalian macrophages can incorporate extracellular vesicles produced by C. neoformans. Incubation of cryptococcal vesicles with murine macrophages resulted in increased levels of extracellular tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10), and transforming growth factor β (TGF-β). Vesicle preparations also resulted in a dose-dependent stimulation of nitric oxide production by phagocytes, suggesting that vesicle components stimulate macrophages to produce antimicrobial compounds. Treated macrophages were more effective at killing C. neoformans yeast. Our results indicate that the extracellular vesicles of C. neoformans can stimulate macrophage function, apparently activating these phagocytic cells to enhance their antimicrobial activity. These results establish that cryptococcal vesicles are biologically active.

Original languageEnglish (US)
Pages (from-to)1601-1609
Number of pages9
JournalInfection and immunity
Volume78
Issue number4
DOIs
StatePublished - Apr 2010

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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    Oliveira, D. L., Freire-de-Lima, C. G., Nosanchuk, J. D., Casadevall, A., Rodrigues, M. L., & Nimrichter, L. (2010). Extracellular vesicles from Cryptococcus neoformans modulate macrophage functions. Infection and immunity, 78(4), 1601-1609. https://doi.org/10.1128/IAI.01171-09