PNNL

Abstract

Cryptococcus neoformans cause a deadly mycosis in immunocompromised individuals. Macrophages are key cells fighting against microbes. Extracellular vesicles (EVs) are cell-to-cell communication mediators. The roles of EVs from infected host in the interaction with Cryptococcus remains elusive. Here, EVs from viable C. neoformans infected macrophages reduced fungal burden but led to shorter survival of infected mice. In vitro, EVs induced naïve macrophages to inflammatory phenotype. Transcriptome analysis showed EVs from viable C. neoformans-infected macrophages activated immune-related pathways including p53 in naïve macrophages from human and murine. Conserved analysis demonstrated basic cell biological process, including cell cycle and division, were activated by infection-derived EVs from both murine and human infected macrophages. Combined proteomics, lipidomics, and metabolomics of EVs from infected macrophages showed regulation of pathways such as ECM-receptor and phosphatidylcholine. This form of inter-macrophage communication could serve to prepare cells at more distant sites of infection to resist C. neoformans infection.