Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Dectin-1 is required for β-glucan recognition and control of fungal infection

Nature Immunology volume 8, pages 31–38 (2007)Cite this article

Abstract

β-Glucan is one of the most abundant polysaccharides in fungal pathogens, yet its importance in antifungal immunity is unclear. Here we show that deficiency of dectin-1, the myeloid receptor for β-glucan, rendered mice susceptible to infection with Candida albicans. Dectin-1-deficient leukocytes demonstrated significantly impaired responses to fungi even in the presence of opsonins. Impaired leukocyte responses were manifested in vivo by reduced inflammatory cell recruitment after fungal infection, resulting in substantially increased fungal burdens and enhanced fungal dissemination. Our results establish a fundamental function for β-glucan recognition by dectin-1 in antifungal immunity and demonstrate a signaling non–Toll-like pattern-recognition receptor required for the induction of protective immune responses.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Dectin-1-deficient mice.
Figure 2: Impaired β-glucan recognition by dectin-1-knockout macrophages.
Figure 3: Impaired β-glucan recognition by dectin-1-knockout neutrophils.
Figure 4: Dectin-1-knockout mice are more susceptible than dectin-1-wild-type mice to live C. albicans.
Figure 5: Kidney disease in dectin-1-knockout mice that succumb to infection.
Figure 6: The function of dectin-1 in the recognition and killing of live fungal particles.
Figure 7: Abnormal antifungal inflammatory response in vivo in the absence of dectin-1.

Similar content being viewed by others

Accession codes

Accessions

Protein Data Bank

References

  1. Romani, L. Immunity to fungal infections. Nat. Rev. Immunol. 4, 1–23 (2004).

    Article  Google Scholar 

  2. Calderone, R.A. & Braun, P.C. Adherence and receptor relationships of Candida albicans. Microbiol. Rev. 55, 1–20 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Gantner, B.N., Simmons, R.M. & Underhill, D.M. Dectin-1 mediates macrophage recognition of Candida albicans yeast but not filaments. EMBO J. 24, 1277–1286 (2005).

    Article  CAS  Google Scholar 

  4. Ross, G.D., Vetvicka, V., Yan, J., Xia, Y. & Vetvickova, J. Therapeutic intervention with complement and β-glucan in cancer. Immunopharmacology 42, 61–74 (1999).

    Article  CAS  Google Scholar 

  5. Tzianabos, A.O. Polysaccharide immunomodulators as therapeutic agents: structural aspects and biologic function. Clin. Microbiol. Rev. 13, 523–533 (2000).

    Article  CAS  Google Scholar 

  6. Ariizumi, K. et al. Identification of a novel, dendritic cell-associated molecule, dectin-1, by subtractive cDNA cloning. J. Biol. Chem. 275, 20157–20167 (2000).

    Article  CAS  Google Scholar 

  7. Brown, G.D. & Gordon, S. Immune recognition. A new receptor for β-glucans. Nature 413, 36–37 (2001).

    Article  CAS  Google Scholar 

  8. Brown, G.D. et al. Dectin-1 mediates the biological effects of β -glucans. J. Exp. Med. 197, 1119–1124 (2003).

    Article  CAS  Google Scholar 

  9. Viriyakosol, S., Fierer, J., Brown, G.D. & Kirkland, T.N. Innate immunity to the pathogenic fungus Coccidioides posadasii is dependent on Toll-like receptor 2 and Dectin-1. Infect. Immun. 73, 1553–1560 (2005).

    Article  CAS  Google Scholar 

  10. Steele, C. et al. Alveolar macrophage-mediated killing of Pneumocystis carinii f. sp. muris involves molecular recognition by the Dectin-1 β-glucan receptor. J. Exp. Med. 198, 1677–1688 (2003).

    Article  CAS  Google Scholar 

  11. Steele, C. et al. The β-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatus. PLoS Pathog. 1, e42 (2005).

    Article  Google Scholar 

  12. Hohl, T.M. et al. Aspergillus fumigatus triggers inflammatory responses by stage-specific β-glucan display. PLoS Pathog 1, e30 (2005).

    Article  Google Scholar 

  13. Gersuk, G.M., Underhill, D.M., Zhu, L. & Marr, K.A. Dectin-1 and TLRs permit macrophages to distinguish between different Aspergillus fumigatus cellular states. J. Immunol. 176, 3717–3724 (2006).

    Article  CAS  Google Scholar 

  14. Gantner, B.N., Simmons, R.M., Canavera, S.J., Akira, S. & Underhill, D.M. Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2. J. Exp. Med. 197, 1107–1117 (2003).

    Article  CAS  Google Scholar 

  15. Underhill, D.M., Rossnagle, E., Lowell, C.A. & Simmons, R.M. Dectin-1 activates Syk tyrosine kinase in a dynamic subset of macrophages for reactive oxygen production. Blood 106, 2543–2550 (2005).

    Article  CAS  Google Scholar 

  16. Herre, J. et al. Dectin-1 uses novel mechanisms for yeast phagocytosis in macrophages. Blood 104, 4038–4045 (2004).

    Article  CAS  Google Scholar 

  17. Rogers, N.C. et al. Syk-dependent cytokine induction by Dectin-1 reveals a novel pattern recognition pathway for C type lectins. Immunity 22, 507–517 (2005).

    Article  CAS  Google Scholar 

  18. Brown, G.D. Dectin-1: a signalling non-TLR pattern-recognition receptor. Nat. Rev. Immunol. 6, 33–43 (2006).

    Article  CAS  Google Scholar 

  19. Taylor, P.R. et al. The β-glucan receptor, dectin-1, is predominantly expressed on the surface of cells of the monocyte/macrophage and neutrophil lineages. J. Immunol. 169, 3876–3882 (2002).

    Article  CAS  Google Scholar 

  20. Di Carlo, F.J. & Fiore, J.V. On the composition of zymosan. Science 127, 756–757 (1958).

    Article  CAS  Google Scholar 

  21. Brown, G.D. et al. Dectin-1 is a major β-glucan receptor on macrophages. J. Exp. Med. 196, 407–412 (2002).

    Article  CAS  Google Scholar 

  22. Nathan, C.F. & Root, R.K. Hydrogen peroxide release from mouse peritoneal macrophages: dependence on sequential activation and triggering. J. Exp. Med. 146, 1648–1662 (1977).

    Article  CAS  Google Scholar 

  23. Gross, O. et al. Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity. Nature 442, 651–656 (2006).

    Article  CAS  Google Scholar 

  24. Cambi, A. et al. The C-type lectin DC-SIGN (CD209) is an antigen-uptake receptor for Candida albicans on dendritic cells. Eur. J. Immunol. 33, 532–538 (2003).

    Article  CAS  Google Scholar 

  25. Bellocchio, S. et al. The contribution of the Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo. J. Immunol. 172, 3059–3069 (2004).

    Article  CAS  Google Scholar 

  26. MacCallum, D.M. & Odds, F.C. Temporal events in the intravenous challenge model for experimental Candida albicans infections in female mice. Mycoses 48, 151–161 (2005).

    Article  Google Scholar 

  27. Netea, M.G. et al. Immune sensing of Candida albicans requires cooperative recognition of mannans and glucans by lectin and Toll-like receptors. J. Clin. Invest. 116, 1642–1650 (2006).

    Article  CAS  Google Scholar 

  28. Brieland, J. et al. Comparison of pathogenesis and host immune responses to Candida glabrata and Candida albicans in systemically infected immunocompetent mice. Infect. Immun. 69, 5046–5055 (2001).

    Article  CAS  Google Scholar 

  29. Taylor, P.R., Brown, G.D., Geldhof, A.B., Martinez-Pomares, L. & Gordon, S. Pattern recognition receptors and differentiation antigens define murine myeloid cell heterogeneity ex vivo. Eur. J. Immunol. 33, 2090–2097 (2003).

    Article  CAS  Google Scholar 

  30. Nathan, C. Neutrophils and immunity: challenges and opportunities. Nat. Rev. Immunol. 6, 173–182 (2006).

    Article  CAS  Google Scholar 

  31. Beutler, B. Tlr4: central component of the sole mammalian LPS sensor. Curr. Opin. Immunol. 12, 20–26 (2000).

    Article  CAS  Google Scholar 

  32. Hoebe, K. et al. CD36 is a sensor of diacylglycerides. Nature 433, 523–527 (2005).

    Article  CAS  Google Scholar 

  33. Hong, F. et al. Mechanism by which orally administered β-1,3-glucans enhance the tumoricidal activity of antitumor monoclonal antibodies in murine tumor models. J. Immunol. 173, 797–806 (2004).

    Article  CAS  Google Scholar 

  34. Rice, P.J. et al. Oral delivery and gastrointestinal absorption of soluble glucans stimulate increased resistance to infectious challenge. J. Pharmacol. Exp. Ther. 314, 1079–1086 (2005).

    Article  CAS  Google Scholar 

  35. Evans, S.E. et al. Pneumocystis cell wall β-glucans stimulate alveolar epithelial cell chemokine generation through nuclear factor-κB-dependent mechanisms. Am. J. Respir. Cell Mol. Biol. 32, 490–497 (2005).

    Article  CAS  Google Scholar 

  36. Wheeler, R.T. & Fink, G.R. A drug-sensitive genetic network masks fungi from the immune system. PLoS Pathog 2, e35 (2006).

    Article  Google Scholar 

  37. Lo, H.J. et al. Nonfilamentous C. albicans mutants are avirulent. Cell 90, 939–949 (1997).

    Article  CAS  Google Scholar 

  38. Gale, C.A. et al. Linkage of adhesion, filamentous growth, and virulence in Candida albicans to a single gene, INT1. Science 279, 1355–1358 (1998).

    Article  CAS  Google Scholar 

  39. Cross, C.E. & Bancroft, G.J. Ingestion of acapsular Cryptococcus neoformans occurs via mannose and β-glucan receptors, resulting in cytokine production and increased phagocytosis of the encapsulated form. Infect. Immun. 63, 2604–2611 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Borges-Walmsley, M.I., Chen, D., Shu, X. & Walmsley, A.R. The pathobiology of Paracoccidioides brasiliensis. Trends Microbiol. 10, 80–87 (2002).

    Article  CAS  Google Scholar 

  41. Grunebach, F., Weck, M.M., Reichert, J. & Brossart, P. Molecular and functional characterization of human Dectin-1. Exp. Hematol. 30, 1309–1315 (2002).

    Article  CAS  Google Scholar 

  42. Willment, J.A., Gordon, S. & Brown, G.D. Characterization of the human β-glucan receptor and its alternatively spliced isoforms. J. Biol. Chem. 276, 43818–43823 (2001).

    Article  CAS  Google Scholar 

  43. Reid, D.M. et al. Expression of the β-glucan receptor, Dectin-1, on murine leukocytes in situ correlates with its function in pathogen recognition and reveals potential roles in leukocyte interactions. J. Leukoc. Biol. 76, 86–94 (2004).

    Article  CAS  Google Scholar 

  44. Willment, J.A. et al. The human β-glucan receptor is widely expressed and functionally equivalent to murine Dectin-1 on primary cells. Eur. J. Immunol. 35, 1539–1547 (2005).

    Article  CAS  Google Scholar 

  45. Willment, J.A. et al. Dectin-1 expression and function are enhanced on alternatively activated and GM-CSF-treated macrophages and are negatively regulated by IL-10, dexamethasone, and lipopolysaccharide. J. Immunol. 171, 4569–4573 (2003).

    Article  CAS  Google Scholar 

  46. Taylor, P.R. et al. The role of SIGNR1 and the β-glucan receptor (dectin-1) in the nonopsonic recognition of yeast by specific macrophages. J. Immunol. 172, 1157–1162 (2004).

    Article  CAS  Google Scholar 

  47. Heinsbroek, S.E.M. et al. Expression of functionally different dectin-1 isoforms by murine macrophages. J. Immunol. 176, 5513–5518 (2006).

    Article  CAS  Google Scholar 

  48. Lutz, M.B. et al. An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. J. Immunol. Methods 223, 77–92 (1999).

    Article  CAS  Google Scholar 

  49. Vonk, A.G., Wieland, C.W., Netea, M.G. & Kullberg, B.J. Phagocytosis and intracellular killing of Candida albicans blastoconidia by neutrophils and macrophages: a comparison of different microbiological test systems. J. Microbiol. Methods 49, 55–62 (2002).

    Article  Google Scholar 

  50. Decleva, E., Menegazzi, R., Busetto, S., Patriarca, P. & Dri, P. Common methodology is inadequate for studies on the microbicidal activity of neutrophils. J. Leukoc. Biol. 79, 87–94 (2006).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the animal facility staff of for care of the animals; and A. Bygrave, P. Norsworthy, L. Fick, M. Tyler, D. Williams, C. Huysamen, L. Graham and C. Maske for help, reagents and technical assistance with the generation and study of the gene-targeted mice and histology. We dedicate this paper to the memory of Albert Beyers. S.G. and G.D.B. share senior authorship. Supported by the Wellcome Trust (055109, 070579, 071467 and 072420; Research Career Development Fellowship, P.R.T.; Senior Fellowship in Biomedical Science in South Africa, G.D.B.), the Cancer Association of South Africa, the Medical Research Council South Africa, the National Institutes of Health (1RO1HL080317) and the Biotechnology and Biological Sciences Research Council (02/B1/P/08210, 60/P17835 and BBS/B/10331).

Author information

Author notes

  1. Philip R Taylor and S Vicky Tsoni: These authors contributed equally to this work.

Authors and Affiliations

  1. Sir William Dunn School of Pathology, University of Oxford, Oxford, OX13RE, UK

    Philip R Taylor, Marcela Rosas & Siamon Gordon

  2. Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, 7925, South Africa

    S Vicky Tsoni, Janet A Willment, Kevin M Dennehy & Gordon D Brown

  3. Imperial College School of Medicine, Hammersmith Campus, London, W12 0NN, UK

    Helen Findon, Ken Haynes & Marina Botto

  4. Department of Pediatrics, Division of Pulmonology, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, 15213, Pennsylvania, USA

    Chad Steele

Authors
  1. Philip R Taylor
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. S Vicky Tsoni
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Janet A Willment
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Kevin M Dennehy
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Marcela Rosas
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Helen Findon
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Ken Haynes
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Chad Steele
    View author publications

    You can also search for this author inPubMed Google Scholar

  9. Marina Botto
    View author publications

    You can also search for this author inPubMed Google Scholar

  10. Siamon Gordon
    View author publications

    You can also search for this author inPubMed Google Scholar

  11. Gordon D Brown
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

P.R.T., S.V.T., J.A.W., K.M.D., M.R., H.F., K.H. and C.S. did the experiments; M.B., G.D.B., P.R.T. and J.A.W. generated the knockout mice; P.R.T., K.H., S.G., C.S. and G.D.B. conceived and directed the experiments; and P.R.T. and G.D.B. wrote the paper.

Corresponding author

Correspondence to Gordon D Brown.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Antigen phenotype of dectin-1-deficient leukocytes. (PDF 1240 kb)

Supplementary Fig. 2

Dectin-1 is dispensable for fungal recognition on dendritic cells. (PDF 336 kb)

Supplementary Fig. 3

Gastrointestinal dissemination of C. albicans in wild-type mice. (PDF 252 kb)

Supplementary Fig. 4

Dectin-1 mediates anti-fungal inflammatory responses in vivo. (PDF 520 kb)

Supplementary Methods (PDF 82 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Taylor, P., Tsoni, S., Willment, J. et al. Dectin-1 is required for β-glucan recognition and control of fungal infection. Nat Immunol 8, 31–38 (2007). https://doi.org/10.1038/ni1408

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ni1408

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing