Dueling in the lung: how Cryptococcus spores race the host for survival

Abstract

Many human fungal pathogens infect people when they are inhaled as spores. Despite the serious impact of fungal spores on human health, little is known about their basic properties or how they interact with the host. This is particularly true for Cryptococcus neoformans, a human fungal pathogen that causes more than 600,000 deaths annually. Spores of C. neoformans have not been well characterized previously because of technical challenges in isolating them; however, recent advances in spore isolation have lead to the first direct analyses of spores. Novel insights into the spore-host interaction, specifically how spores interact with alveolar macrophages, have provided a new model of cryptococcosis that could have broad implications for human fungal pathogenesis.

Figure 1. C. neoformans spores are covered by a thick spore coat

The left panel is a scanning electron micrograph of a C. neoformans spore, showing the characteristic polar morphology with a stalk-like structure on the bottom and a crenulated surface (Bar = 500 nm). The right panel shows a transmission electron micrograph displaying a cross section of a C. neoformans spore. The arrow indicates the thick spore coat, which is a heterogeneous structure containing striations of varying electron density (Bar 500 nm).

Figure 2. The kinetic model of C. neoformans spore-mediated infections

Inhaled spores are phagocytosed by alveolar macrophages. Rapid activation of the macrophage leads to the production of ROI and RNI (stars) before the spores have completed germination, thus killing and clearing the spores. Delayed activation of the macrophages allows the spores to germinate into yeast, which are capable of withstanding the ROI and RNI. These yeast then persist and grow within the macrophage.