Candida albicans subverts host programmed cell death: a unified framework from pyroptosis to ferroptosis.
4 affiliations
- 1Department of Laboratory, Dermatology Hospital, Southern Medical University, Guangzhou, China.
- 2The Second Affiliated Hospital, The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, Guangzhou Medical University, Guangzhou, China.
- 3Nanfang Hospital, Southern Medical University, Guangzhou, China.
- 4Department of Pathology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
Abstract
Candida albicans is a major opportunistic fungal pathogen that causes substantial morbidity and mortality, particularly in immunocompromised individuals. Increasing evidence indicates that its pathogenicity extends beyond classical virulence traits and involves active engagement of host programmed cell death (PCD) pathways. In this review, we propose a unified mechanistic framework to explain how C. albicans virulence programs-including hyphal morphogenesis, candidalysin-mediated epithelial injury, cell wall remodeling, and metabolic adaptation-interact with host sensing systems to shape distinct yet interconnected forms of cell death. Among the currently implicated pathways, pyroptosis is the most strongly supported and represents the clearest link between fungal invasion, inflammasome activation, and inflammatory tissue injury. By contrast, apoptosis appears to be more heterogeneous and context-dependent, whereas necroptosis and ferroptosis remain emerging mechanisms whose contributions likely vary across cell types, tissues, and stages of infection. We further examine how host compartments, including epithelial cells, macrophages, neutrophils, and IL-17-associated immune circuits, amplify, buffer, or redirect these death responses, thereby influencing the balance between fungal clearance and immunopathology. Particular emphasis is placed on tissue specificity, as the biological consequences of PCD differ markedly across oral, vaginal, intestinal, hepatic, and disseminated candidiasis. Finally, we discuss the translational implications of this framework for host-directed antifungal strategies and argue that therapeutic modulation of cell death will require careful attention to timing, tissue context, and preservation of protective immunity. This review provides an evidence-weighted and integrative perspective on how C. albicans subverts host cell death and how these processes may be leveraged for future therapeutic innovation.
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BibTeX
@article{fan2026candida,
title = {{Candida albicans subverts host programmed cell death: a unified framework from pyroptosis to ferroptosis.}},
author = {Limin Fan and Ruining Huang and Kexin Wang and Manting Ni and Xiuyu Nong and Zhenmou Xie and Bo Fu and Lijun Mo and Yinyuan Lan and Qingqing Xu and Wenhan Cao and Xinyue Li and Xueting Liu and Yaohua Xue},
journal = {Frontiers in cellular and infection microbiology},
year = {2026},
month = oct,
doi = {10.3389/fcimb.2026.1960578},
url = {https://europepmc.org/article/MED/42923838},
note = {CC BY},
}
RIS
TY - JOUR
TI - Candida albicans subverts host programmed cell death: a unified framework from pyroptosis to ferroptosis.
AU - Limin Fan
AU - Ruining Huang
AU - Kexin Wang
AU - Manting Ni
AU - Xiuyu Nong
AU - Zhenmou Xie
AU - Bo Fu
AU - Lijun Mo
AU - Yinyuan Lan
AU - Qingqing Xu
AU - Wenhan Cao
AU - Xinyue Li
AU - Xueting Liu
AU - Yaohua Xue
PY - 2026
DA - 2026/10/08
JO - Frontiers in cellular and infection microbiology
DO - 10.3389/fcimb.2026.1960578
UR - https://europepmc.org/article/MED/42923838
AB - Candida albicans is a major opportunistic fungal pathogen that causes substantial morbidity and mortality, particularly in immunocompromised individuals. Increasing evidence indicates that its pathogenicity extends beyond classical virulence traits and involves active engagement of host programmed cell death (PCD) pathways. In this review, we propose a unified mechanistic framework to explain how C. albicans virulence programs-including hyphal morphogenesis, candidalysin-mediated epithelial injury, cell wall remodeling, and metabolic adaptation-interact with host sensing systems to shape distinct yet interconnected forms of cell death. Among the currently implicated pathways, pyroptosis is the most strongly supported and represents the clearest link between fungal invasion, inflammasome activation, and inflammatory tissue injury. By contrast, apoptosis appears to be more heterogeneous and context-dependent, whereas necroptosis and ferroptosis remain emerging mechanisms whose contributions likely vary across cell types, tissues, and stages of infection. We further examine how host compartments, including epithelial cells, macrophages, neutrophils, and IL-17-associated immune circuits, amplify, buffer, or redirect these death responses, thereby influencing the balance between fungal clearance and immunopathology. Particular emphasis is placed on tissue specificity, as the biological consequences of PCD differ markedly across oral, vaginal, intestinal, hepatic, and disseminated candidiasis. Finally, we discuss the translational implications of this framework for host-directed antifungal strategies and argue that therapeutic modulation of cell death will require careful attention to timing, tissue context, and preservation of protective immunity. This review provides an evidence-weighted and integrative perspective on how C. albicans subverts host cell death and how these processes may be leveraged for future therapeutic innovation.
SN - 2235-2988
ER -