The triple threat of cryptococcosis: it's the body site, the strain, and/or the host.

Cryptococcosis is the leading invasive fungal infection in the world today. Over the past century, the causative agents, Cryptococcus neoformans and Cryptococcus gattii, have risen from the status of medical curiosities to common but life-threatening central nervous system pathogens. In an elegant experimental pathobiology study of these two organisms carried out by Ngamskulrungroj et al., there are three matters that merit further discussion. First is the question of whether there is a variable specific pathobiology for each yeast strain. Does it make biological and clinical sense to designate C. neoformans and C. gattii as two separate species? Second is the matter of how the organisms differ pathologically at the site of infection. Finally, there is the possibility that the human immune system responds differently to each species. Although no single study can provide definitive mechanistic answers to the important questions, this experimental pathology study and its discussion clearly frame the issues to be dissected.