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

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.

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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.

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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).

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Authors

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.

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Correspondence to Gordon D Brown.

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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)

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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

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