Abstract
Cryptococcus neoformans is a common environmental saprophyte and human fungal pathogen that primarily causes disease in immunocompromised individuals. Similar to many environmentally acquired human fungal pathogens, C. neoformans initiates infection in the lungs. However, the main driver of mortality is invasive cryptococcosis leading to fungal meningitis. After C. neoformans gains a foothold in the lungs, a critical early step in invasion is transversal of the respiratory epithelium. In this review, we summarize current knowledge relating to pulmonary escape. We focus on fungal factors that allow C. neoformans to disseminate from the lungs via intracellular and extracellular routes.
Highlights
The lungs present a mucosal barrier that is in constant contact with airborne microbes, including fungi
Experiments in zebrafish found that most C. neoformans cells are found outside macrophages at 2 h post-inoculation but that almost >50% of fungal cells were found within macrophages at 24 hpi [29]
The cell surface capsule is necessary for cryptococcal cell survival following phagocytosis, as acapsular cells cannot replicate inside macrophages [24]
Summary
The lungs present a mucosal barrier that is in constant contact with airborne microbes, including fungi. The lung epithelium plays a constitutive role in regulating microbial load through mechanisms such as secretion of antimicrobial defensins and mucociliary clearance [6] Both resident professional immune cells and epithelial cells are capable of sensing and coordinating immune responses to microbes [7]. J. Fungi 2018, 4, 25 is reliant on robust cell-mediated immunity, characterized broadly by a T-helper 1 (Th1) profile [17]. Fungi 2018, 4, 25 is reliant on robust cell-mediated immunity, characterized broadly by a T-helper 1 (Th1) profile [17] This includes production of cytokines such as interleukin 12 (IL-12), interferon gamma (IFNγ), tumor necrosis factor alpha (TNFα), and classically activated, or M1, skewing monocytes/macrophages [17]. We explore processes leading to C. neoformans’s escape from the lungs and dissemination throughout the host
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