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¹ Immunobiology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, London WC2A 3PX, England, UK
² Department of Infection, Immunity, and Biochemistry, School of Medicine, Cardiff University, Cardiff CF14 4XN, Wales, UK
³ Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal
⁴ National Institute for Medical Research, London NW7 1AA, England, UK
⁵ III. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany
⁶ Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, Netherlands
⁷ Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, Scotland, UK
⁸ Laboratory of Signaling in the Immune System, Helmholtz-Zentrum München–German Research Center for Environmental Health, 85764 Neuherberg, Germany

CORRESPONDENCE Caetano Reis e Sousa: caetano{at}cancer.org.uk

Innate immune cells detect pathogens via pattern recognition receptors (PRRs), which signal for initiation of immune responses to infection. Studies with Dectin-1, a PRR for fungi, have defined a novel innate signaling pathway involving Syk kinase and the adaptor CARD9, which is critical for inducing Th17 responses to fungal infection. We show that another C-type lectin, Dectin-2, also signals via Syk and CARD9, and contributes to dendritic cell (DC) activation by fungal particles. Unlike Dectin-1, Dectin-2 couples to Syk indirectly, through association with the FcR chain. In a model of Candida albicans infection, blockade of Dectin-2 did not affect innate immune resistance but abrogated Candida-specific T cell production of IL-17 and, in combination with the absence of Dectin-1, decreased Th1 responses to the organism. Thus, Dectin-2 constitutes a major fungal PRR that can couple to the Syk–CARD9 innate signaling pathway to activate DCs and regulate adaptive immune responses to fungal infection.

P.R. Taylor and C. Reis e Sousa contributed equally to this paper.

Abbreviations used: BMDC, bone marrow–derived DC; CLR, C-type lectin receptor; ITAM, immunoreceptor tyrosine-based activation motif; NLR, NOD-like receptor; PAMP, pathogen-associated molecular pattern; PRR, pattern recognition receptor; RLR, RIG-I–like receptor; shRNA, short hairpin RNA; TLR, Toll-like receptor.

© 2009 Robinson et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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This article has been cited by other articles:

• Robinson, M. J., Osorio, F., Rosas, M., Freitas, R. P., Schweighoffer, E., Gross, O., Verbeek, J. S., Ruland, J., Tybulewicz, V., Brown, G. D., Moita, L. F., Taylor, P. R., e Sousa, C. R. (2009). Dectin-2 is a Syk-coupled pattern recognition receptor crucial for Th17 responses to fungal infection. JCB 186: i9-i9 [Full Text]  

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