Dectin-2 recognition of alpha-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans.
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 alpha-mannan-induced cytokine production. Dectin-2 signaling induced cytokines through an FcRgamma chain and Syk-CARD9-NF-kappaB-dependent signaling pathway without involvement of MAP kinases. The yeast form of C. albicans induced interleukin-1beta (IL-1beta) 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.
Saijo
Shinobu
S
Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku Tokyo 108-8639, Japan.
Ikeda
Satoshi
S
Yamabe
Keiko
K
Kakuta
Shigeru
S
Ishigame
Harumichi
H
Akitsu
Aoi
A
Fujikado
Noriyuki
N
Kusaka
Toshimasa
T
Kubo
Sachiko
S
Chung
Soo-hyun
SH
Komatsu
Ryohei
R
Miura
Noriko
N
Adachi
Yoshiyuki
Y
Ohno
Naohito
N
Shibuya
Kazutoshi
K
Yamamoto
Natsuo
N
Kawakami
Kazuyoshi
K
Yamasaki
Sho
S
Saito
Takashi
T
Akira
Shizuo
S
Iwakura
Yoichiro
Y
D000818:Animals; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D007118:Immunoassay; D020381:Interleukin-17 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000276:immunology; D053759:Interleukin-23 / Q000276:immunology; D037181:Lectins, C-Type / Q000235:genetics / Q000276:immunology*; D008297:Male; D008351:Mannans / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology
D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D037181:Lectins, C-Type; D008351:Mannans; C445340:dectin-2, mouse