Dual-transcriptome analyses of high- and low-virulence strains of Cryptococcus gattii cocultured with RAW264.7 macrophages.

Abstract

Cryptococcus gattii (C. gattii) is an aggressive fungus that can infect both immunocompetent and immunosuppressed hosts. As a first line of immunity in humans, macrophages can phagocytose and kill C. gattii; yet macrophages can also provide a favorable ecological niche for its proliferation and immune escape. Using dual-transcriptome analysis, which allows for the exploration of transcriptional expression levels in pathogen-host interactions, we aimed to quantitatively measure host (RAW264.7 macrophage) immune responses to strains of C. gattii with different virulence, including transcriptional changes in both host and fungus. We evaluated 31 strains of C. gattii and divided them into high virulence (HV) and low virulence (LV) based on phenotype. Compared to the LV strains, the HV strains inhibited development of M1 macrophages, killing of the HV strains by macrophages was weaker, and transcription levels of virulence and growth genes were increased. We also found that macrophages after contact with HV C. gattii strains had high expression of genes related to cell adhesion but lower expression of those related to antigen presentation, immune response, and oxidative stress. Inhibition of macrophage immune response to HV C. gattii was confirmed in vitro and in vivo. Our data add to what is known about the mechanisms of immune escape by C. gattii.