C-Type Lectin Receptor CD23 Is Required for Host Defense against and Infection.

Infection by invasive fungi, such as , , and , is one of the leading death causes for the increasing population of immunocompromised and immunodeficient patients. Several C-type lectin receptors (CLRs), including Dectin-1, -2, and -3 and Mincle can recognize fungal surface components and initiate the host antifungal immune responses. Nevertheless, it remains to be determined whether other CLRs are involved in antifungal immunity. Our recent study suggests that CD23 (CLEC4J), a CLR and also a well-known B cell surface marker, may function to sense components in antifungal immunity. However, it is not clear how CD23 functions as a fungal pattern recognition receptor and whether the antifungal role of CD23 is specific to or not. In this study, we show that CD23 can recognize both α-mannan and β-glucan from the cell wall of or but cannot recognize glucuronoxylomannan from Through forming a complex with FcRγ, CD23 can induce NF-κB activation. Consistently, CD23-deficient mice were highly susceptible to and but not to infection. The expression of CD23 in activated macrophages is critical for the activation of NF-κB. CD23 deficiency results in impaired expression of NF-κB-dependent genes, especially , which induces NO production to suppress fungal infection. Together, our studies reveal the CD23-induced signaling pathways and their roles in antifungal immunity, specifically for and , which provides the molecular basis for designing potential therapeutic agents against fungal infection.