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      Pattern recognition: recent insights from Dectin-1

      review-article
      1 , 1 , 1 , 2
      Current Opinion in Immunology
      Elsevier

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          Abstract

          The β-glucan receptor Dectin-1 is an archetypical non-toll-like pattern recognition receptor expressed predominantly by myeloid cells, which can induce its own intracellular signalling and can mediate a variety of cellular responses, such as cytokine production. Recent identification of the components of these signalling pathways, such as Syk kinase, CARD9 and Raf-1, has provided novel insights into the molecular mechanisms underlying Dectin-1 function. Furthermore, a broader appreciation of the cellular responses mediated by this receptor and the effects of interactions with other receptors, including the TLRs, have greatly furthered our understanding of innate immunity and how this drives the development of adaptive immunity, particularly Th17 responses. Recent studies have highlighted the importance of Dectin-1 in anti-fungal immunity, in both mice and humans, and have suggested a possible involvement of this receptor in the control of mycobacterial infections.

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          Most cited references41

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          Recognition of microorganisms and activation of the immune response.

          The mammalian immune system has innate and adaptive components, which cooperate to protect the host against microbial infections. The innate immune system consists of functionally distinct 'modules' that evolved to provide different forms of protection against pathogens. It senses pathogens through pattern-recognition receptors, which trigger the activation of antimicrobial defences and stimulate the adaptive immune response. The adaptive immune system, in turn, activates innate effector mechanisms in an antigen-specific manner. The connections between the various immune components are not fully understood, but recent progress brings us closer to an integrated view of the immune system and its function in host defence.
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            Dectin-1 is required for beta-glucan recognition and control of fungal infection.

            Beta-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 beta-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 beta-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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              Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17.

              The C-type lectin dectin-1 binds to yeast and signals through the kinase Syk and the adaptor CARD9 to induce production of interleukin 10 (IL-10) and IL-2 in dendritic cells (DCs). However, whether this pathway promotes full DC activation remains unclear. Here we show that dectin-1-Syk-CARD9 signaling induced DC maturation and the secretion of proinflammatory cytokines, including IL-6, tumor necrosis factor and IL-23, but little IL-12. Dectin-1-activated DCs 'instructed' the differentiation of CD4+ IL-17-producing effector T cells (T(H)-17 cells) in vitro, and a dectin-1 agonist acted as an adjuvant promoting the differentiation of T(H)-17 and T helper type 1 cells in vivo. Infection with Candida albicans induced CARD9-dependent T(H)-17 responses to the organism. Our data indicate that signaling through Syk and CARD9 can couple innate to adaptive immunity independently of Toll-like receptor signals and that CARD9 is required for the development of T(H)-17 responses to some pathogens.
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                Author and article information

                Contributors
                Journal
                Curr Opin Immunol
                Current Opinion in Immunology
                Elsevier
                0952-7915
                1879-0372
                February 2009
                February 2009
                : 21
                : 1
                : 30-37
                Affiliations
                [1 ]Section of Immunology and Infection, Division of Applied Medicine, Institute of Medical Sciences, Foresterhill, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom
                [2 ]Division of Immunology, CLS, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa
                Article
                COIMMU694
                10.1016/j.coi.2009.01.003
                2684021
                19223162
                46d96ef0-263b-4be4-a8dc-4b0e66035e09
                © 2009 Elsevier Ltd.

                This document may be redistributed and reused, subject to certain conditions.

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                Immunology
                Immunology

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