Candidalysin, the first cytolytic toxin identified in a human fungal pathogen, triggers release of antimicrobial peptides from epithelial cells through EGFR-MAPK signaling.
First fungal toxincandidalysin triggers the release of anti-Candida antimicrobial peptides from epithelial cells, linking pathogen invasion to host defense activation
What the researchers found
Candidalysin, the first cytolytic peptide toxin identified in a human fungal pathogen, triggered release of multiple key immune molecules from epithelial cells:
Alarmins (danger signals) and antimicrobial peptides with known anti-Candida activity were released in response to candidalysin. The specific molecules were not all named in the abstract but include key innate immune effectors.
The signaling mechanism was novel: extracellular ATP released during candidalysin-mediated cell damage activated EGFR (epidermal growth factor receptor) and MAPK (mitogen-activated protein kinase) signaling cascades. These pathways then drove the downstream antimicrobial peptide and cytokine response.
This is important because it identifies the exact fungal factor responsible for triggering innate immune defense at mucosal surfaces during oral Candida infection.
Why it matters
Candida infections range from oral thrush to life-threatening systemic disease, especially in immunocompromised patients. Understanding how the body first detects Candida through candidalysin-triggered AMP release could lead to therapies that boost this natural defense. It also explains why certain immune deficiencies lead to severe Candida infections.
The numbers in context
Multiple AMPs and alarmins released; ATP-EGFR-MAPK pathway; candidalysin is first cytolytic fungal toxin; oral epithelial model
How the study worked
In vitro study using oral epithelial cell infection models. Cells were exposed to candidalysin and wild-type Candida albicans. Alarmin and AMP release were measured. Signaling pathways (EGFR, MAPK) were characterized using inhibitors and pathway analysis. ATP was measured as a mediator.
Who was studied
Oral epithelial cells infected with Candida albicans/candidalysin
What this study cannot tell us
In vitro study using oral epithelial cells. The specific AMPs and alarmins released were identified but the full panel is best described in the full paper. In vivo confirmation in animal models or human tissue is needed. The role of ATP as a mediator needs further characterization in complex tissue environments.
How to read the evidence
Moderate evidence from well-designed in vitro infection models. The signaling pathway is clearly mapped but in vivo significance needs confirmation.
When this study was published
Published in 2020. Candidalysin biology has become a major focus in fungal immunology research.
The bigger picture
Candida infections range from mild thrush to life-threatening systemic disease. Understanding how epithelial cells first detect and respond to Candida through candidalysin-triggered antimicrobial peptides could lead to therapies that boost natural defenses in immunocompromised patients.
Questions still open
- Could boosting candidalysin-triggered AMP responses prevent Candida infections in immunocompromised patients?
- Does candidalysin sensitivity vary between individuals?
- Are there Candida strains with altered candidalysin production that evade this response?
Common questions
What is candidalysin?
Could this help treat Candida infections?
Read the original research
Candidalysin Is a Potent Trigger of Alarmin and Antimicrobial Peptide Release in Epithelial Cells.
Cells, 9(3)
Citation
Ho, Jemima; Wickramasinghe, Don N; Nikou, Spyridoula-Angeliki; Hube, Bernhard; Richardson, Jonathan P; Naglik, Julian R. (2020). Candidalysin Is a Potent Trigger of Alarmin and Antimicrobial Peptide Release in Epithelial Cells.. Cells, 9(3). https://doi.org/10.3390/cells9030699