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Dectin-1 is required for host defense against Pneumocystis carinii but not against Candida albicans

Nature Immunology volume 8, pages 39–46 (2007)Cite this article

Abstract

Dectin-1 is a C-type lectin involved in the recognition of β-glucans found in the cell walls of fungi. We generated dectin-1-deficient mice to determine the importance of dectin-1 in the defense against pathogenic fungi. In vitro, β-glucan-induced cytokine production from wild-type dendritic cells and macrophages was abolished in cells homozygous for dectin-1 deficiency ('dectin-1-knockout' cells). In vivo, dectin-1-knockout mice were more susceptible than wild-type mice to pneumocystis infection, even though their cytokine production was normal. However, pneumocystis-infected dectin-1-knockout macrophages did show defective production of reactive oxygen species. In contrast to those results, wild-type and dectin-1-knockout mice were equally susceptible to candida infection. Thus, dectin-1 is required for immune responses to some fungal infections, as protective immunity to pneumocystis, but not to candida, required dectin-1 for the production of antifungal reactive oxygen species.

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Figure 1: Cytokine induction by β-glucans is dependent on dectin-1.
Figure 2: BMDC maturation is induced by β-glucans via dectin-1.
Figure 3: Antigen presentation by dectin-1-knockout dendritic cells is normal.
Figure 4: Dectin-1-knockout mice are more susceptible than dectin-1-wild-type mice to P. carinii infection.
Figure 5: Dectin-1 is not required for defense against C. albicans.

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Acknowledgements

DO11.10 mice were provided by D.Y. Loh (Washington University School of Medicine). Supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and the Ministry of Health and Welfare of Japan (Y.I. and S.S.) and by the Japan Society for the Promotion of Science (N.F.).

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Authors and Affiliations

  1. Center for Experimental Medicine. The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Shinobu Saijo, Noriyuki Fujikado, Soo-hyun Chung, Hayato Kotaki, Keisuke Seki, Katsuko Sudo & Yoichiro Iwakura

  2. Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan

    Takahisa Furuta

  3. Department of Host Defense, Research Institute for Microbial Disease, Osaka University, 3-1 Yamadaoka, Suita-shi, Osaka, 565-0871, Japan

    Shizuo Akira

  4. Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1423-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan

    Yoshiyuki Adachi & Naohito Ohno

  5. Department of Medicine and Therapeutics, Control and Prevention of Infectious Diseases, Faculty of Medicine, University of the Ryukyu, 207 Uehara, Nishihara-cho, Nakagami-gunn, Okinawa, 903-0215, Japan

    Takeshi Kinjo & Kiwamu Nakamura

  6. Department of Medical Technology, Microbiology and Immunology, School of Health Science, Tohoku University, 2-1, Seiryou-cho, Aoba-ku, Sendai-shi, Miyagi, 980-8575, Japan

    Kazuyoshi Kawakami

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  1. Shinobu Saijo
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Contributions

S.S. mainly contributed throughout this work in collaboration with N.F., S.C. and K. Seki; H.K. and K. Sudo did embryonic stem cell culture and produced chimeric mice; Y.A. and N.O. made β-glucan preparations and did cytokine production experiments; T.F. did in vivo P. carinii experiments and provided P. carinii for the in vitro experiments; T.K., K.N. and K.K. did in vivo C. albicans experiments; S.A. provided Myd88−/− mice; and Y.I. supervised the study, designed the experiments and edited the draft paper.

Corresponding author

Correspondence to Yoichiro Iwakura.

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Supplementary information

Supplementary Fig. 1

Generation of dectin-1-deficient mice. (PDF 147 kb)

Supplementary Fig. 2

Survival and fungal burdens of C. albicans–infected mice. (PDF 354 kb)

Supplementary Methods (PDF 81 kb)

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Saijo, S., Fujikado, N., Furuta, T. et al. Dectin-1 is required for host defense against Pneumocystis carinii but not against Candida albicans. Nat Immunol 8, 39–46 (2007). https://doi.org/10.1038/ni1425

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