[PDF][PDF] Dectin-2 recognition of α-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans

S Saijo, S Ikeda, K Yamabe, S Kakuta, H Ishigame… - Immunity, 2010 - cell.com
S Saijo, S Ikeda, K Yamabe, S Kakuta, H Ishigame, A Akitsu, N Fujikado, T Kusaka, S Kubo…
Immunity, 2010cell.com
Summary Dectin-2 (gene symbol Clec4n) is a C-type lectin expressed by dendritic cells
(DCs) and macrophages. However, its functional roles and signaling mechanisms remain to
be elucidated. Here, we generated Clec4n−/− mice and showed that this molecule is
important for host defense against Candida albicans (C. albicans). Clec4n−/− DCs had
virtually no fungal α-mannan-induced cytokine production. Dectin-2 signaling induced
cytokines through an FcRγ chain and Syk-CARD9-NF-κB-dependent signaling pathway …
Summary
Dectin-2 (gene symbol Clec4n) is a C-type lectin expressed by dendritic cells (DCs) and macrophages. However, its functional roles and signaling mechanisms remain to be elucidated. Here, we generated Clec4n−/− mice and showed that this molecule is important for host defense against Candida albicans (C. albicans). Clec4n−/− DCs had virtually no fungal α-mannan-induced cytokine production. Dectin-2 signaling induced cytokines through an FcRγ chain and Syk-CARD9-NF-κB-dependent signaling pathway without involvement of MAP kinases. The yeast form of C. albicans induced interleukin-1β (IL-1β) and IL-23 secretion in a Dectin-2-dependent manner. In contrast, cytokine production induced by the hyphal form was only partially dependent on this lectin. Both yeast and hyphae induced Th17 cell differentiation, in which Dectin-2, but not Dectin-1, was mainly involved. Because IL-17A-deficient mice were highly susceptible to systemic candida infection, this study suggests that Dectin-2 is important in host defense against C. albicans by inducing Th17 cell differentiation.
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