Immunological Mechanisms in Candida albicans Infections

Candida albicans is a ubiquitous fungal commensal that can transition to an opportunistic pathogen when host defences are impaired. Recognition of C. albicans by epithelial cells and innate immune sensors initiates a cascade of responses, beginning with pattern recognition receptors such as Toll-like receptors and C-type lectin receptors. These receptors detect fungal cell-wall components, notably β-glucans and mannans, and trigger phagocytosis by neutrophils and macrophages, production of reactive oxygen species and formation of neutrophil extracellular traps. Secretion of candidalysin and other virulence factors by the fungus provokes epithelial damage and amplifies pro-inflammatory cytokine release. Downstream, interleukin-17 and interleukin-22 produced by Th17 cells orchestrate mucosal protection, while interleukin-12 and interferon-γ drive Th1 responses that are critical for systemic defence. Humoral responses contribute through antibody-mediated opsonisation and complement activation. Candida albicans employs immune-evasion strategies such as morphological switching, biofilm formation and protease secretion to subvert host barriers. Understanding the balance between protective inflammation and immunopathology is essential for designing targeted therapies and vaccines that restore host–fungus homeostasis.

Research from Nature Portfolio

Recent studies have examined how modulation of cytokine signalling affects antifungal immunity. Investigation of Janus kinase inhibition revealed that blockade of downstream signalling of pro-inflammatory cytokines markedly impairs the fungicidal capacity of neutrophils. In murine models and human cells, suppression of TNFα, interferon-γ and GM-CSF signalling reduced reactive oxygen species production, neutrophil extracellular trap formation and phagocytic killing of C. albicans. These findings underscore the delicate requirement for intact cytokine networks to mount effective innate responses and caution against long-term targeting of these pathways without monitoring for opportunistic fungal infections.

Immunological Mechanisms in Candida albicans Infections publication trend

The graph below shows the total number of articles in immunological mechanisms in candida albicans infections across all publications each year (not limited to Nature Index journals).

Technical terms

Pattern recognition receptor (PRR): a host cell receptor that recognises conserved microbial molecules and triggers innate immune responses.

Neutrophil extracellular trap (NET): a DNA-based network expelled by neutrophils that traps and kills pathogens extracellularly.

Th17 cell: a subset of CD4+ T lymphocytes that produce interleukin-17 and drive neutrophil recruitment to mucosal surfaces.

Candidalysin: a peptide toxin secreted by C. albicans hyphae that damages host cells and activates inflammatory signalling.

Morphological switching: the reversible transition between yeast and filamentous forms in C. albicans, essential for tissue invasion and immune evasion.

References

1. Interleukin inhibitors and the associated risk of candidiasis. Frontiers in Immunology (2024).
2. A study on the risk of fungal infection with tofacitinib (CP-690550), a novel oral agent for rheumatoid arthritis. Scientific Reports (2017).
3. IL‐12 and Related Cytokines: Function and Regulatory Implications in Candida albicans Infection. Journal of Immunology Research (2010).
4. Effect of Gliotoxin on Human Polymorphonuclear Neutrophils. Infectious Diseases in Obstetrics and Gynecology (1998).