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Publication : C-Type Lectin Receptor CD23 Is Required for Host Defense against <i>Candida albicans</i> and <i>Aspergillus fumigatus</i> Infection.

First Author  Guo Y Year  2018
Journal  J Immunol Volume  201
Issue  8 Pages  2427-2440
PubMed ID  30185519 Mgi Jnum  J:266216
Mgi Id  MGI:6203340 Doi  10.4049/jimmunol.1800620
Citation  Guo Y, et al. (2018) C-Type Lectin Receptor CD23 Is Required for Host Defense against Candida albicans and Aspergillus fumigatus Infection. J Immunol 201(8):2427-2440
abstractText  Infection by invasive fungi, such as Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans, 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 C. albicans 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 C. albicans or not. In this study, we show that CD23 can recognize both alpha-mannan and beta-glucan from the cell wall of C. albicans or A. fumigatus but cannot recognize glucuronoxylomannan from Cryptococcus Through forming a complex with FcRgamma, CD23 can induce NF-kappaB activation. Consistently, CD23-deficient mice were highly susceptible to C. albicans and A. fumigatus but not to C. neoformans infection. The expression of CD23 in activated macrophages is critical for the activation of NF-kappaB. CD23 deficiency results in impaired expression of NF-kappaB-dependent genes, especially iNOS, 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 C. albicans and A. fumigatus, which provides the molecular basis for designing potential therapeutic agents against fungal infection.
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