Catch me if you can: phagocytosis and killing avoidance by Cryptococcus neoformans.

After inhalation of infectious particles, Cryptococcus neoformans resides in the alveolar spaces, where it can survive and replicate in the extracellular environment. This yeast has developed different mechanisms to avoid internalization by phagocytic cells, the main one being a polysaccharide capsule around the cell body, which inhibits the uptake of the yeast by macrophages. In addition, capsule-independent mechanisms have also been described, such as the production of antiphagocytic proteins. Despite these mechanisms, phagocytosis can occur in the presence of opsonins, and once C. neoformans is internalized, multiple outcomes are possible, including pathogen killing or intracellular replication and escape from macrophages. For this reason, C. neoformans is considered a facultative intracellular pathogen. As alveolar macrophages are the first component of the host immune system to confront C. neoformans, the outcome of this interaction could determine the degree of infection, producing either a severe disseminated disease or a latency state. In this review, we will tackle the complexity of the interaction between C. neoformans and macrophages, including the phagocytic avoidance mechanisms and all the possible outcomes that have been described for this interaction. Finally, we will discuss the consequences of the different outcomes for the type of infection produced in the host.