Cryptococcus is a yeast commonly found in soil, decaying wood and bird excreta. Normally characterized as an opportunistic human infection, cryptococcosis is a leading cause of meningitis and death in HIV/AIDS patients in Sub-Saharan Africa. Recent Cryptococcus gattii outbreaks within healthy, immunocompetent populations in the Pacific Northwest are calling this characterization into question. Recent studies support the ability of Cryptococcus to replicate intracellularly, particularly in macrophages, leading to classification as a facultative intracellular pathogen. However, in vivo analysis of this capacity for intracellular replication in the context of a disease model for pulmonary infection has been lacking. Here we employ a GFP expressing strain of Cryptococcus neoformans and present novel dye labeling strategies to assess whether intracellular replication is productive in a mouse model of pulmonary cryptococcosis. We show that, while limited intracellular replication occurs, cryptococcal clearance by alveolar macrophages within the first forty-eight hours of pulmonary infection predominates. Cryptococcus may correctly be characterized as a facultative intracellular pathogen; however, alveolar macrophages possess the capacity to clear this pathogen, keeping early infection in check. Our finding, showing the importance of the alveolar macrophage in early cryptococcal clearance, opens the possibility of novel treatment strategies for a clinically important human pathogen.
- Copyright © 2013 by The American Association of Immunologists, Inc.