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Updated: Jun 19, 2026
Candida albicans Biofilm Development on Medically-relevant Foreign Bodies in a Mouse Subcutaneous Model Followed by Bioluminescence Imaging
Published on: January 27, 2015
Inhibition of CBLB protects from lethal Candida albicans sepsis
Gerald Wirnsberger1, Florian Zwolanek2, Tomoko Asaoka1
1Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria.
Abstract:
Fungal infections claim an estimated 1.5 million lives each year. Mechanisms that protect from fungal infections are still elusive. Recognition of fungal pathogens relies on C-type lectin receptors (CLRs) and their downstream signaling kinase SYK. Here we report that the E3 ubiquitin ligase CBLB controls proximal CLR signaling in macrophages and dendritic cells. We show that CBLB associates with SYK and ubiquitinates SYK, dectin-1, and dectin-2 after fungal recognition. Functionally, CBLB deficiency results in increased inflammasome activation, enhanced reactive oxygen species production, and increased fungal killing. Genetic deletion of Cblb protects mice from morbidity caused by cutaneous infection and markedly improves survival after a lethal systemic infection with Candida albicans. On the basis of these findings, we engineered a cell-permeable CBLB inhibitory peptide that protects mice from lethal C. albicans infections. We thus describe a key role for Cblb in the regulation of innate antifungal immunity and establish a novel paradigm for the treatment of fungal sepsis.
Insights
The E3 ubiquitin ligase CBLB regulates innate antifungal immunity by controlling C-type lectin receptor (CLR) signaling. Inhibiting CBLB enhances fungal killing and protects against lethal Candida albicans infections.
Area of Science:
- Immunology
- Microbiology
- Biochemistry
Background:
- Fungal infections cause significant mortality, with protective mechanisms poorly understood.
- Pathogen recognition involves C-type lectin receptors (CLRs) and the SYK signaling kinase.
Purpose of the Study:
- To investigate the role of the E3 ubiquitin ligase CBLB in innate antifungal immunity.
- To explore CBLB as a therapeutic target for fungal infections.
Main Methods:
- Studied CBLB's interaction with SYK and CLRs (dectin-1, dectin-2) in macrophages and dendritic cells.
- Assessed inflammasome activation, reactive oxygen species production, and fungal killing in Cblb-deficient models.
- Evaluated a CBLB inhibitory peptide in mouse models of Candida albicans infection.
Main Results:
- CBLB ubiquitinates SYK, dectin-1, and dectin-2 upon fungal recognition.
- CBLB deficiency enhances inflammasome activation, ROS production, and fungal clearance.
- Genetic deletion of Cblb and CBLB inhibition protect mice from fungal infections.
Conclusions:
- CBLB is a critical regulator of proximal CLR signaling in antifungal immunity.
- Targeting CBLB represents a novel therapeutic strategy for treating fungal sepsis and infections.
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