TY - JOUR
T1 - Dectin-2 recognition of α-mannans and induction of Th17 cell differentiation is essential for host defense against candida albicans
AU - Saijo, Shinobu
AU - Ikeda, Satoshi
AU - Yamabe, Keiko
AU - Kakuta, Shigeru
AU - Ishigame, Harumichi
AU - Akitsu, Aoi
AU - Fujikado, Noriyuki
AU - Kusaka, Toshimasa
AU - Kubo, Sachiko
AU - Chung, Soo hyun
AU - Komatsu, Ryohei
AU - Miura, Noriko
AU - Adachi, Yoshiyuki
AU - Ohno, Naohito
AU - Shibuya, Kazutoshi
AU - Yamamoto, Natsuo
AU - Kawakami, Kazuyoshi
AU - Yamasaki, Sho
AU - Saito, Takashi
AU - Akira, Shizuo
AU - Iwakura, Yoichiro
N1 - Funding Information:
We deeply thank G.N. Barber for critical reading of the manuscript; N. Sato and A. Shibuya for their technical assistance; Y. Ishii for cell sorting; T. Chibana for SC5314 strain of C. albicans; and all of the members of our laboratory for animal care. This work was supported by CREST of the Japan Science and Technology Corporation, the Promotion of Basic Research Activities for Innovative Biosciences, Grants-in Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, the Health Science Research Grant for Research on Emerging and Re-emerging Infectious Diseases, The Health Science Research Grant for Measures for Intractable Diseases from Ministry of Health, Labour, and Welfare of Japan, and The Grant of the Strategic Basis on Research Grounds from Ministry of Education, Culture, Sports, Science, and Technology of Japan.
PY - 2010/5
Y1 - 2010/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77953289487&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77953289487&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2010.05.001
DO - 10.1016/j.immuni.2010.05.001
M3 - Article
C2 - 20493731
AN - SCOPUS:77953289487
SN - 1074-7613
VL - 32
SP - 681
EP - 691
JO - Immunity
JF - Immunity
IS - 5
ER -
