Abstract
Cryptococcus neoformans is a human pathogenic fungus that mainly afflicts immunocompromised patients. One of its virulence strategies is the production of extracellular vesicles (EVs), containing cargo with immunomodulatory properties. We evaluated EV’s characteristics produced by capsular and acapsular strains of C. neoformans (B3501 and ΔCap67, respectively) growing in nutritionally poor or rich media and co-cultures with bone marrow-derived macrophages or dendritic cells from C57BL/6 mice. EVs produced under a poor nutritional condition displayed a larger hydrodynamic size, contained more virulence compounds, and induced a more robust inflammatory pattern than those produced in a rich nutritional medium, independently of strain. We treated infected mice with EVs produced in the rich medium, and the EVs inhibited more genes related to the inflammasome than untreated infected mice. These findings suggest that the EVs participate in the pathogenic processes that result in the dissemination of C. neoformans. Thus, these results highlight the versatility of EVs’ properties during infection by C. neoformans in different tissues and support ongoing efforts to harness EVs to prevent and treat cryptococcosis.
Highlights
Cryptococcus neoformans is an environmental basidiomycetous yeast-like fungus
Dynamic light scattering (DLS) experiments revealed that both strains produced vesicles of different sizes when grown in different media
We show that a stressful microenvironment with low nutrient availability results in C. neoformans producing extracellular vesicles (EVs) that are larger than those produced in a rich medium, in addition to exhibiting a higher content of virulence factors such as GXM, acid phosphatase, urease, laccase, and heat shock proteins
Summary
Cryptococcus neoformans is an environmental basidiomycetous yeast-like fungus. Mammals can inhale the spores or desiccated yeast, which transition to a yeast-like form and, if they avoid or subvert host immune responses, cause cryptococcosis. Infection in immunocompetent individuals typically results in an asymptomatic acquisition of the fungus or mild, self-limited pneumonia. The fungi are usually eliminated or became latent, which can result in reactivation disease if the host immune system subsequently becomes compromised [3]. When C. neoformans infects individuals with defective cell-mediated immunity, especially those deficient in CD4+ T lymphocytes, the yeasts can migrate from the lung to cause disease in any organ, including the central nervous system (CNS) to cause a meningoencephalitis, which is uniformly lethal without antimicrobial therapy [4]
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