Candida albicans subverts host programmed cell death: a unified framework from pyroptosis to ferroptosis

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.