Maintaining phagosome integrity during fungal infection: do or die?
Authors:Mabel Yang1, Glenn F.W. Walpole1,2 and Johannes Westman1
doi: 10.15698/mic2020.12.738
Volume 7, pp. 323 to 325, published 03/12/2020.
1 Program in Cell Biology, The Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada.
2 Department of Biochemistry, University of Toronto, Toronto, ON, M5S 1A8, Canada.
Keywords:
Candida albicans, phagosome, lysosome, macrophage, fungi, calcium
Corresponding Author(s):
Conflict of interest statement:
The authors declare no conflict of interests.
Please cite this article as:
Mabel Yang, Glenn F.W. Walpole and Johannes Westman (2020). Maintaining phagosome integrity during fungal infection: do or die? Microbial Cell 7(12): 323-325. doi: 10.15698/mic2020.12.738
© 2020 Yang et al. This is an open-access article released under the terms of the Crea-tive Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Professional phagocytes represent a critical node in innate immunity and tissue homeostasis through their specialized ability to eat, drink, and digest material from the extracellular milieu. The degradative and microbicidal functions of phagocytes rely on the fusion of lysosomes with endosomal compartments such as phagosomes, resulting in the digestion and recycling of internalized prey and debris. Despite these efforts, several particularly dangerous infections result from a class of tenacious pathogens that resist digestion, often surviving and even proliferating within the confines of the phagosomal membrane. One such example, Candida albicans, is a commensal polymorphic fungus that colonizes ~50% of the population and can cause life-threatening infections in immunocompromised patients. Not only can C. albicans survive within phagosomes, but its ingestion by macrophages triggers a yeast-to-hyphal transition promoting rapid intraphagosomal growth (several microns per hour) while imposing a substantial mechanical burden on the phagosomal membrane surrounding the fungus. Preservation of membrane integrity is essential to maintain the hostile internal environment of the phagosome, a functionality of degradative enzymes and oxidative stress. Yet, biological membranes such as phagosomes have a limited capacity to stretch. Using C. albicans as a model intracellular pathogen, our recent work reveals a mechanism by which phagosomes respond to intraphagosomal growth of pathogens by expanding their surface area, and as a result, maintain the integrity of the phagosomal membrane. We hypothesized that this expansion would be facilitated by the delivery and fusion of membrane from extraneous sources with the phagosome. Consistently, macrophages respond to the yeast-to-hyphal transition through a stretch-induced release of phagosomal calcium, leading to recruitment and insertion of lysosomes that accommodate the expansion of the phagolysosome and preserve its integrity. Below, we discuss this calcium-dependent mechanism of lysosome insertion as a means of avoiding phagosomal rupture. Further, we examine the implications of membrane integrity on the delicate balance between the host and pathogen by focusing on fungal stress responses, nutrient acquisition, inflammasome activation, and cell death.