Related Experiment Video
Updated: Oct 12, 2025
Live-cell Video Microscopy of Fungal Pathogen Phagocytosis
Published on: January 9, 2013
Inflammasome-mediated GSDMD activation facilitates escape of Candida albicans from macrophages
Xionghui Ding1,2, Hiroto Kambara1, Rongxia Guo1,3
1Department of Pathology, Dana-Farber/Harvard Cancer Center, Harvard Medical School; Department of Laboratory Medicine, Boston Children's Hospital, Enders Research Building, Room 814, Boston, MA, 02115, USA.
Abstract:
Candida albicans is the most common cause of fungal sepsis. Inhibition of inflammasome activity confers resistance to polymicrobial and LPS-induced sepsis; however, inflammasome signaling appears to protect against C. albicans infection, so inflammasome inhibitors are not clinically useful for candidiasis. Here we show disruption of GSDMD, a known inflammasome target and key pyroptotic cell death mediator, paradoxically alleviates candidiasis, improving outcomes and survival of Candida-infected mice. Mechanistically, C. albicans hijacked the canonical inflammasome-GSDMD axis-mediated pyroptosis to promote their escape from macrophages, deploying hyphae and candidalysin, a pore-forming toxin expressed by hyphae. GSDMD inhibition alleviated candidiasis by preventing C. albicans escape from macrophages while maintaining inflammasome-dependent but GSDMD-independent IL-1β production for anti-fungal host defenses. This study demonstrates key functions for GSDMD in Candida's escape from host immunity in vitro and in vivo and suggests that GSDMD may be a potential therapeutic target in C. albicans-induced sepsis.
Insights
Disrupting GSDMD, a cell death mediator, surprisingly improves survival in mice with fungal sepsis caused by Candida albicans. This strategy blocks fungal escape from immune cells while preserving protective inflammation.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- * Candida albicans is a primary cause of fungal sepsis.
- * Inflammasome inhibition protects against some sepsis types but may worsen Candida infections.
- * GSDMD is a key mediator of pyroptosis, a form of programmed cell death.
Purpose of the Study:
- * To investigate the role of GSDMD in Candida albicans sepsis.
- * To explore GSDMD inhibition as a potential therapeutic strategy for candidiasis.
Main Methods:
- * Used a mouse model of Candida albicans infection.
- * Assessed the impact of GSDMD disruption on survival and fungal dissemination.
- * Investigated the mechanisms of fungal escape from macrophages.
Main Results:
- * GSDMD disruption improved survival and outcomes in mice with candidiasis.
- * Candida albicans utilizes the inflammasome-GSDMD pathway to escape macrophages via hyphae and candidalysin.
- * GSDMD inhibition prevented fungal escape and maintained IL-1β production.
Conclusions:
- * GSDMD plays a critical role in Candida albicans' evasion of host immunity.
- * Inhibiting GSDMD offers a novel therapeutic approach for Candida sepsis.
- * GSDMD-independent IL-1β production is crucial for anti-fungal defense.
