Impact of the Environment upon the Candida albicans Cell Wall and Resultant Effects upon Immune Surveillance

Abstract

The fungal cell wall is an essential organelle that maintains cellular morphology and protects the fungus from environmental insults. For fungal pathogens such as Candida albicans, it provides a degree of protection against attack by host immune defences. However, the cell wall also presents key epitopes that trigger host immunity, and attractive targets for antifungal drugs. Rather than being a rigid shield, it has become clear that the fungal cell wall is an elastic organelle that permits rapid changes in cell volume and the transit of large liposomal particles such as extracellular vesicles. The fungal cell wall is also flexible in that it adapts to local environmental inputs, thereby enhancing the fitness of the fungus in these microenvironments. Recent evidence indicates that this cell wall adaptation affects hostfungus interactions by altering the exposure of major cell wall epitopes that are recognised by innate immune cells. Therefore, we discuss the impact of environmental adaptation upon fungal cell wall structure and immune evasion, focussing on C. albicans and drawing parallels with other fungal pathogens.

The impact of the Fungus-Host-Microbiota interplay uponCandida albicansinfections: current knowledge and new perspectives

“…N -linked mannans are highly branched structures that form the fibrils in the outer layer of the wall (Gow, Latge and Munro 2017 ; Childers et al . 2019 ). The functions of about 70% of cell wall mannoproteins remain obscure, but some are known or suspected to be involved in the infection process (De Groot, Ram and Klis 2005 ; Richard and Plaine 2007 ).…”

Clinical Candida albicans Vaginal Isolates and a Laboratory Strain Show Divergent Behaviors during Macrophage Interactions

“…Elevated Th17-mediated cytokine secretion (interleukin-22 [IL-22], Il-17A, and IL-17F) and inflammasome activation, followed by IL-1β cleavage, also accompanies this process of hyperinflammatory immune cell infiltration into the vaginal tissues, which is largely responsible for the observed clinical symptoms ( 7 ). In this context, nutritional prerequisites have been shown to play an important role in modeling the fungal cell wall architecture and subsequent immune cell recognition ( 8 , 9 ). In particular, lactate, a predominant carbon source in the vaginal tract ( 10 ) has been shown to influence host pathogen interaction and infection outcomes ( 11 – 13 ).…”

Adapting to survive: How Candida overcomes host-imposed constraints during human colonization

“…PPRs mediate binding of the pathogen to the phagocyte, and the PAMP-PRR interactions trigger intracellular signaling pathways within the immune cells that can induce phagocytosis and the production of proinflammatory cytokines and chemokines. In order to attenuate recognition and escape phagocytosis, Candida cells are able to actively mask cell-wall PAMPs [129] and secrete specific proteases that target complement opsonization [130]. Alternatively, some Candida species can induce their phagocytic uptake into endothelial and epithelial cells and use these cells as "safe houses" by preventing maturation of the phagolysosome and subsequent killing [131].…”