Titan cells in Cryptococcus neoformans: cells with a giant impact

Cryptococcus neoformans is a pathogenic yeast that commonly infects immunocompromised individuals, yet has developed multiple adaptation mechanisms to the host. Several virulence factors (capsule and melanin) have been known for many years. However, this yeast also possesses a morphogenetic program that is still not well characterized. C. neoformans has the ability to dramatically enlarge its size during infection to form 'titan cells' that can reach up to 100 μm in cell body diameter, in contrast to typical size cells of 5-7 μm. These titan cells pose a problem for the host because they contribute to fungal survival, dissemination to the central nervous system, and possibly even latency. In this review, we will provide an overview of these cells, covering current knowledge about their phenotypic features, mechanism of formation, and their significance during infection.