It’s a big week for Cryptococcus neoformans at mBio. Two new papers describe insights into how the pathogen interacts with the body’s macrophages, those big eaters of the immune system that should (but often don’t) gobble up C. neoformans before it can do real harm. In chronic C. neoformans infections, the pathogen is often found inside macrophage phagosomes where it may be living as a facultative intercellular pathogen. Getting to the bottom of how the fungus gets in and out of macrophages could help in the development of new therapies for the infection.
First: a discovery about how C. neoformans escapes from macrophages through a process called non-lytic exocytosis. Nicola et al. noted that scientists have observed neoformans escaping from intact macrophages in vitro, but no one knew how important this mode of escape might be in the body. They developed a method using flow cytometry that can monitor the process and used it to explore the process in mice with C. neoformans infections. They proved that non-lytic exocytosis could play a bigger role than previously appreciated: the process occurred in vivo at a much higher frequency than observed in vitro. These results in turn suggest that non-lytic exocytosis has potential role in the pathogenesis of cryptococcosis.
Next up is a paper by Alanio et al. that examines how differences in C. neoformans clinical isolates impact the outcome of infection. Until now, the interactions between C. neoformans and host cells has mostly been studied using reference or mutant strains of the pathogen and few studies describe the effects of C. neoformans diversity on infections. Like Nicola et al., Alanio et al. developed a flow cytometry assay to study the dynamics of macrophage-C. neoformans interactions. By deploying several different clinical isolates of C. neoformans, Alanio et al. demonstrated that under the same experimental conditions, clinical isolates behave differently and these differences could well have important effects – for better or worse – on outcomes for patients.
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