CD137 Signaling Is Critical in Fungal Clearance during Systemic Infection.

Invasive fungal infections by frequently cause mortality in immunocompromised patients. Neutrophils are particularly important for fungal clearance during systemic infection, yet little has been known regarding which surface receptor controls neutrophils' antifungal activities. CD137, which is encoded by , 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 infection. We first found that mice were susceptible to infection, whereas injection of anti-CD137 agonistic antibody protected the host from infection, suggesting that CD137 signaling is indispensable for innate immunity against 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 mice that received wild-type (WT) neutrophils. In conclusion, our results demonstrate that CD137 signaling contributes to defense mechanisms against systemic infection by promoting rapid fungal clearance.