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Updated: Nov 3, 2025
Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis
Published on: March 19, 2019
CD137 Signaling Is Critical in Fungal Clearance during Systemic Candida albicans Infection
Vuvi G Tran1, Na N Z Nguyen1, Byungsuk Kwon1
1School of Biological Science, University of Ulsan, Ulsan 44610, Korea.
Abstract:
Invasive fungal infections by Candida albicans frequently cause mortality in immunocompromised patients. Neutrophils are particularly important for fungal clearance during systemic C. albican infection, yet little has been known regarding which surface receptor controls neutrophils' antifungal activities. CD137, which is encoded by Tnfrsf9, belongs to the tumor necrosis receptor superfamily and has been shown to regulate neutrophils in Gram-positive bacterial infection. Here, we used genetic and immunological tools to probe the involvement of neutrophil CD137 signaling in innate defense mechanisms against systemic C. albicans infection. We first found that Tnfrsf9-/- mice were susceptible to C. albicans infection, whereas injection of anti-CD137 agonistic antibody protected the host from infection, suggesting that CD137 signaling is indispensable for innate immunity against C. albicans infection. Priming of isolated neutrophils with anti-CD137 antibody promoted their phagocytic and fungicidal activities through phospholipase C. In addition, injection of anti-CD137 antibody significantly augmented restriction of fungal growth in Tnfrsf9-/- mice that received wild-type (WT) neutrophils. In conclusion, our results demonstrate that CD137 signaling contributes to defense mechanisms against systemic C. albicans infection by promoting rapid fungal clearance.
Insights
Neutrophil CD137 signaling is crucial for fighting invasive Candida albicans infections. Activating CD137 enhances neutrophil antifungal activity, improving fungal clearance in immunocompromised patients.
Area of Science:
- Immunology
- Infectious Diseases
- Microbiology
Background:
- Invasive fungal infections, particularly by Candida albicans, pose a significant threat to immunocompromised individuals.
- Neutrophils are key players in clearing systemic C. albicans infections, but the specific surface receptors governing their antifungal functions remain largely unknown.
- CD137 (Tnfrsf9) is a tumor necrosis receptor superfamily member known to modulate neutrophil responses in bacterial infections.
Purpose of the Study:
- To investigate the role of neutrophil CD137 signaling in the innate immune defense against systemic Candida albicans infection.
- To determine if CD137 activation enhances neutrophil phagocytic and fungicidal capabilities against C. albicans.
Main Methods:
- Utilized genetic approaches, including Tnfrsf9 knockout (Tnfrsf9-/-) mice.
- Employed immunological tools such as anti-CD137 agonistic antibodies.
- Assessed neutrophil phagocytosis and fungicidal activity in vitro and fungal clearance in vivo.
Main Results:
- Tnfrsf9-/- mice exhibited increased susceptibility to C. albicans infection.
- Administration of anti-CD137 agonistic antibody conferred protection against systemic C. albicans infection.
- Priming neutrophils with anti-CD137 antibody enhanced their phagocytic and fungicidal activities via phospholipase C.
- Anti-CD137 antibody treatment improved fungal growth restriction in Tnfrsf9-/- mice reconstituted with wild-type neutrophils.
Conclusions:
- CD137 signaling is essential for effective innate immunity against systemic Candida albicans infections.
- CD137 activation by specific antibodies boosts neutrophil-mediated antifungal defense mechanisms.
- Targeting CD137 signaling represents a potential therapeutic strategy to enhance fungal clearance in immunocompromised patients.
