Dectin-1 synergizes with TLR2 and TLR4 for cytokine production in human primary monocytes and macrophages

Ferwerda, Gerben; Meyer‐Wentrup, Friederike; Kullberg, Bart‐Jan; Netea, Mihai G.; Adema, Gosse J.

doi:10.1111/j.1462-5822.2008.01188.x

Cited by 306 publications

(269 citation statements)

References 47 publications

(59 reference statements)

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“…This is important because it has been welldescribed that ''cross-talk'' between the TLR2/4 and Dectin-1 is responsible for the synergy of proinflammatory response mounted by the host [32][33][34]. Our use of pure TLR2, TLR4, and Dectin-1 ligands, as well as TLR2/Dectin-1 and TLR4/Dectin-1 ligand combination, illustrated the profound influence that 1,25(OH) 2 D 3 exerted beyond its effect on the individual PRR.…”

Section: Discussionmentioning

confidence: 99%

1,25-dihydroxyvitamin D3 Modulates Cytokine Production Induced by Candida albicans: Impact of Seasonal Variation of Immune Responses

Khoo

Chai

Koenen

et al. 2011

The Journal of Infectious Diseases

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Background. Our interest in immunological effects produced by vitamin D 3 (1,25(OH) 2 D 3 ) and its therapeutic potential prompted us to examine the role of 1,25(OH) 2 D 3 on cytokine production by Candida albicans.Methods. Peripheral blood mononuclear cells (PBMC) with stimulated C. albicans and 1,25(OH) 2 D 3 , cytokine concentrations were measured in supernatant. Quantitative polymerase chain reaction (qPCR) was performed for T cell transcription factors, SOCS1 and 3. TLR2/4, Dectin-1, and mannose receptor expression was studied using flow cytometry and qPCR. An ex-vivo stimulation study was carried out in healthy volunteers to investigate the seasonality of immune response to C. albicans.Results. Upon in vitro C. albicans stimulation, 1,25(OH) 2 D 3 induced a dose-dependent, down-regulation of IL-6, TNFa, IL-17, and IFNc. It also increased IL-10 production. The shift in cytokine profile was not due to 1,25(OH) 2 D 3 augmenting expression of either Thelper differentiation factors or SOCS1 and SOCS3 mRNA. 1,25(OH) 2 D 3 inhibited TLR2, TLR4, Dectin-1, and MR mRNA and protein expression. In our seasonality study, both IL-17 and IFNc levels were suppressed in summer when 25(OH)D 3 levels were elevated.Conclusion. Vitamin D 3 skews cytokine responses toward an antiinflammatory profile, mediated by suppression of TLR2, TLR4, Dectin-1, and MR transcription, leading to reduced surface expression. The biological relevance of these effects has been confirmed by the seasonality of cytokine responses.

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Section: Discussionmentioning

confidence: 99%

1,25-dihydroxyvitamin D3 Modulates Cytokine Production Induced by Candida albicans: Impact of Seasonal Variation of Immune Responses

Khoo

Chai

Koenen

et al. 2011

The Journal of Infectious Diseases

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“…In this study, it was first revealed that MCP-1 was produced through Dectin-1-mediated signal transduction by using curdlan, a specific agonist of Dectin-1, in mast cells in a TLR2-independent manner (Fig. 6B) (52,53). IL-4 and IL-13, canonical type 2 cytokines, are closely related cytokines required for the generation of high-affinity IgE antibodies, mucus overproduction, and smooth muscle alterations (54).…”

Section: Discussionmentioning

confidence: 99%

Dectin-1-mediated Signaling Leads to Characteristic Gene Expressions and Cytokine Secretion via Spleen Tyrosine Kinase (Syk) in Rat Mast Cells

Kimura

Chihara

Honjoh

et al. 2014

Journal of Biological Chemistry

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Background: ␤-Glucan receptor Dectin-1 in dendritic cells and macrophages plays important roles in antifungal immunity. Results: Dectin-1 is expressed in rat mast cells, and its tyrosine phosphorylation induces characteristic gene expression of transcription factors and cytokines through protein-tyrosine kinase Syk. Conclusion: Dectin-1 functions in rat mast cells. Significance: Dectin-1-mediated signaling in mast cells may contribute to antifungal immunity.

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“…Recent data suggest that glycan-induced CLR signaling can modulate inflammatory responses by enhancing or suppressing TLR-mediated responses (59,60). Especially the C-type lectin DC-SIGN shows interesting properties that are often, but not always, associated with Th2 polarization, suppression of inflammation and induction of a regulatory function (61)(62)(63).…”

Section: Can Helminth Compounds Suppress Inflammatory Responses Of DCmentioning

confidence: 99%

Worms to the rescue: Can worm glycans protect from autoimmune diseases?

Kuijk

Die

2010

IUBMB Life

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Autoimmune and autoinflammatory diseases represent a significant health burden, especially in Western societies. For the majority of these diseases, no cure exists. Recently, research on parasitic worms (helminths) has demonstrated great potential for whole worms, their eggs or their excretory/secretory proteins in down‐regulating inflammatory responses both in vitro and in vivo, in various disease models and, in some cases, even in clinical trials. The worms are thought to induce Th2 and regulatory T cells, interfere with Toll‐like receptor (TLR) signaling and to down‐regulate Th17 and Th1 responses. The molecular mechanisms underlying the worms' ability to modulate the host immune response are not well understood, and many hypotheses have been proposed to explain the observed immune modulation. Increasing evidence suggests that carbohydrate structures (glycans), for example, phosphorylcholine‐modified glycans or Galβ1‐4(Fucα1‐3)GlcNAc‐ (Lewis X, LeX) containing glycans, expressed by the worms contribute to these modulating properties by their interaction with antigen presenting cells. Helminths express a broad variety of protein‐ and lipid‐linked glycans on their surface and on secretory products. These glycans differ in amount and composition and several of these structures are species specific. However, worms also express glycan antigens that are found in a wide variety of different species. Some of these “common” worm glycans are particularly interesting with regard to regulating host responses, because they have the potential to interact with C‐type lectins on dendritic cells and thereby may interfere with T‐cell polarization. Helminths and helminth‐derived molecules form a novel and promising group of therapeutics for autoinflammatory diseases. However, much has to be learned about the molecular mechanisms behind the helminth‐mediated antiinflammatory properties. This review will describe some of the emerging evidence in selected disease areas as well as discuss the putative role of glycans in helminth‐mediated immunosuppression. © 2010 IUBMB IUBMB Life, 62(4): 303–312, 2010

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Dectin-1 synergizes with TLR2 and TLR4 for cytokine production in human primary monocytes and macrophages

Cited by 306 publications

References 47 publications

1,25-dihydroxyvitamin D3 Modulates Cytokine Production Induced by Candida albicans: Impact of Seasonal Variation of Immune Responses

1,25-dihydroxyvitamin D3 Modulates Cytokine Production Induced by Candida albicans: Impact of Seasonal Variation of Immune Responses

Dectin-1-mediated Signaling Leads to Characteristic Gene Expressions and Cytokine Secretion via Spleen Tyrosine Kinase (Syk) in Rat Mast Cells

Worms to the rescue: Can worm glycans protect from autoimmune diseases?

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