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CD137 Signaling Is Critical in Fungal Clearance during Systemic Candida albicans Infection.

Authors
  • Tran, Vuvi G1
  • Nguyen, Na N Z1
  • Kwon, Byungsuk1
  • 1 School of Biological Science, University of Ulsan, Ulsan 44610, Korea. , (North Korea)
Type
Published Article
Journal
Journal of fungi (Basel, Switzerland)
Publication Date
May 14, 2021
Volume
7
Issue
5
Identifiers
DOI: 10.3390/jof7050382
PMID: 34068963
Source
Medline
Keywords
Language
English
License
Unknown

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.

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