Paradoxical roles of alveolar macrophages in the host response to Cryptococcus neoformans

Cryptococcus neoformans (Cn) is a fungal pathogen that is a serious health threat to immunocompromised individuals. Upon environmental exposure, infectious fungal propagules are inhaled into the host's lungs. The anticryptococcal actions of alveolar macrophages (AM), the predominant host phagocyte of the innate immune system in the lungs, are fundamental in determining whether containment and clearance of the pathogen occurs by the development of an adapted immune response or whether infection is established and progresses to disease. However, the fungus is also capable of surviving the antimicrobial actions of AM and exploits these host phagocytes to establish infection and exacerbate disease. In addition, there is evidence suggesting that cryptococcosis may occur following reactivation of latent cryptococcal infection. Currently, the role of AM and the fungal factors contributing to latent cryptococcosis are unknown. This review examines the AM-Cn interaction and how it affects the development of pulmonary disease with a focus on host and pathogen factors enabling latency to occur.