Unmasking Candidiasis: A Mechanistic Model for Innate Immune-Fungal Cell Wall Dynamics

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Hidu, Erica
Candidiasis; cell wall dynamics; Candida albicans; fungal pathogen; in vitro; fungal cell wall and innate immune system; systemic candidiasis; Microbiology; Other Microbiology
thesis / dissertation description
Candida albicans is an opportunistic fungal pathogen that can cause a potentially lethal systemic infection in immunocompromised patients. Increasing drug resistance of Candida species to anti-fungal treatments makes the study of this pathogen ever more important. Study of the C. albicans cell wall provides insight into its importance in pathogenesis, immune recognition, and anti-fungal action. It has been shown that β- glucan, a masked component of the fungal cell wall and ligand for the immune receptor Dectin-1, becomes available for immune recognition in the mouse model of systemic candidiasis. To develop a mechanistic model to explain this unmasking, we investigated the interaction between the C. albicans cell wall and the innate immune system in vitro. Our research suggests that neutrophils can wrap around fungal filaments and release components of their lysosomes, including proteases, onto the cell wall. This interaction can result in damage to cell wall-associated proteins and the subsequent unmasking of β- glucan. Our research also suggests that proteases can mediate this unmasking. We speculate these neutrophil-damaged fungal filaments may elicit a greater proinflammatory response from innate immune cells through increased recognition by Dectin-1. Our research sheds light on the interactions between the fungal cell wall and the innate immune system, which could lead to more efficacious treatments for those suffering from systemic candidiasis.