Abstract
The theoretical physicist and Nobel laureate Richard Feynman outlined in his 1959 lecture, “There’s plenty of room at the bottom”, the enormous possibility of producing and visualising things at smaller scales. The advent of advanced scanning and transmission electron microscopy and high-resolution microscopy has begun to open the door to visualise host-pathogen interactions at smaller scales, and spinning disc confocal and two-photon microscopy has improved our ability to study these events in real time in three dimensions. The aim of this review is to illustrate some of the advances in understanding host-fungal interactions that have been made in recent years in particular those relating to the interactions of live fungal pathogens with phagocytes. Dynamic imaging of host-pathogen interactions has recently revealed novel detail and unsuspected mechanistic insights, facilitating the dissection of the phagocytic process into its component parts. Here, we will highlight advances in our knowledge of host-fungal pathogen interactions, including the specific effects of fungal cell viability, cell wall composition and morphogenesis on the phagocytic process and try to define the relative contributions of neutrophils and macrophages to the clearance of fungal pathogens in vitro and the infected host.
Highlights
Fungal infections contribute substantially to human morbidity and mortality
A study by Lewis et al utilised widefield live video microscopy [24] to dissect minute-by-minute the phagocytosis process of C. albicans by macrophages and developed a method to determine phagocyte migratory kinetics (Fig. 3), with which they showed migration towards C. albicans is dependent on the glycosylation status of the fungal cell wall, but not cell viability or morphogenic switching from yeast to hyphal forms [25]
This study demonstrated that the rate of engulfment of C. albicans tethered to the macrophage surface is significantly delayed for glycosylation and yeast-locked morphogenetic mutant strains, but enhanced for non-viable cells [25]
Summary
Fungal infections contribute substantially to human morbidity and mortality. Over 1.5 billion people suffer from fungal infections. An essential component of the innate response to fungal infection involves macrophages and PMNs recognising pathogen-associated molecular patterns (PAMPs) present in the fungal cell wall through pattern recognition receptors (PRRs) localised on the phagocytic cell membrane, endosomes and cytoplasm [9, 10].
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