The Cryptococcus neoformans titan cell: from in vivo phenomenon to in vitro model

Purpose of review: During infection, the human fungal pathogen Cryptococcus neoformans undergoes an unusual change in size, from small haploid yeast to large polyploid Titan cells. This transition is now well recognized as a virulence factor, but significant questions remain about how Titanisation is regulated and how it influences disease progression. Progress has been impeded by the lack of an in vitro model for the yeast-to-Titan transition, a challenge that was recently overcome by three independent groups.

Recent findings: Here, we review Titanization in the context of patient samples and animal models and set the stage for three new reports describing in vitro Titan cell induction assays. We compare and contrast key findings, place them in the broader research context, and identify areas of further interest.

Summary: New in vitro models will allow pressing questions about molecular mechanisms driving the yeast-to-Titan transition and their influence on drug resistance and pathogenesis to be addressed.