Tran, V.G.; Nguyen, N.N.Z.; Kwon, B. CD137 Signaling Is Critical in Fungal Clearance during Systemic Candida albicans Infection. J. Fungi2021, 7, 382.
Tran, V.G.; Nguyen, N.N.Z.; Kwon, B. CD137 Signaling Is Critical in Fungal Clearance during Systemic Candida albicans Infection. J. Fungi 2021, 7, 382.
Tran, V.G.; Nguyen, N.N.Z.; Kwon, B. CD137 Signaling Is Critical in Fungal Clearance during Systemic Candida albicans Infection. J. Fungi2021, 7, 382.
Tran, V.G.; Nguyen, N.N.Z.; Kwon, B. CD137 Signaling Is Critical in Fungal Clearance during Systemic Candida albicans Infection. J. Fungi 2021, 7, 382.
Abstract
Invasive fungal infections by Candida albicans frequently cause mortality in immunocompromised patients. Neutrophils are particularly important for fungal clearance at the early phase of infections, yet little has been known regarding which surface receptor controls neutrophil phagocytic activities during systemic C. albicans infection. 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 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 WT neutrophils. In conclusion, our results demonstrate that CD137 signaling contributes to defense mechanisms against systemic C. albicans infection by promoting rapid fungal clearance whereby harmful immunopathology-induced tissue injuries are minimalized.
Biology and Life Sciences, Biochemistry and Molecular Biology
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