Fucose-based PAMPs prime dendritic cells for follicular T helper cell polarization via DC-SIGN-dependent IL-27 production

Gringhuis, Sonja I.; Kaptein, Tanja M.; Wevers, Brigitte A.; Vlist, Michiel van der; Klaver, Elsenoor J.; Die, Irma van; Vriend, Lianne; Jong, Marein A. W. P. de; Geijtenbeek, Teunis B. H.

doi:10.1038/ncomms6074

Cited by 86 publications

(84 citation statements)

References 52 publications

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“…Previous works have demonstrated that DC-SIGN interacts with glycan structures from a variety of pathogens ranging from virus to fungi3. In fact DC-SIGN binds glycoconjugates from HIV4, coronavirus5, herpes simplex virus6, Helicobacter pylori 4, Mycobacterium tuberculosis 478, Candida albicans 9, as well as cancer-related glycans10. More recently, different papers have reported that DC-SIGN also interacts with glycans form parasites, thereby modulating the immune response.…”

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confidence: 99%

“…The interaction of DC-SIGN with pathogens, triggers specific signaling events that modulate DC activity at various levels, influencing phagocytosis16, suppressing TLR-induced maturation of DCs15, internalizing pathogen-derived molecules12, modifying DC-adhesion and migration17 and antigen presentation181920, and regulating T-cell activation by DCs47. In addition, DC-SIGN has also been involved in the induction of anti-inflammatory signals that result in the induction of anergic T cells21.…”

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confidence: 99%

“…In addition, DC-SIGN has also been involved in the induction of anti-inflammatory signals that result in the induction of anergic T cells21. Interestingly, it has been recently reported that extracts from S. mansoni eggs and F. hepatica worms trigger a DC-SIGN specific signaling pathway on DCs that directs differentiation of T cells into follicular helper T cells7.…”

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confidence: 99%

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Fasciola hepatica glycoconjugates immuneregulate dendritic cells through the Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin inducing T cell anergy

Rodríguez

Kalay

Noya

et al. 2017

Sci Rep

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Dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) expressed on a variety of DCs, is a C-type lectin receptor that recognizes glycans on a diverse range of pathogens, including parasites. The interaction of DC-SIGN with pathogens triggers specific signaling events that modulate DC-maturation and activity and regulate T-cell activation by DCs. In this work we evaluate whether F. hepatica glycans can immune modulate DCs via DC-SIGN. We demonstrate that DC-SIGN interacts with F. hepatica glycoconjugates through mannose and fucose residues. We also show that mannose is present in high-mannose structures, hybrid and trimannosyl N-glycans with terminal GlcNAc. Furthermore, we demonstrate that F. hepatica glycans induce DC-SIGN triggering leading to a strong production of TLR-induced IL-10 and IL-27p28. In addition, parasite glycans induced regulatory DCs via DC-SIGN that decrease allogeneic T cell proliferation, via the induction of anergic/regulatory T cells, highlighting the role of DC-SIGN in the regulation of innate and adaptive immune responses by F. hepatica. Our data confirm the immunomodulatory properties of DC-SIGN triggered by pathogen-derived glycans and contribute to the identification of immunomodulatory glyans of helminths that might eventually be useful for the design of vaccines against fasciolosis.

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confidence: 99%

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confidence: 99%

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confidence: 99%

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Fasciola hepatica glycoconjugates immuneregulate dendritic cells through the Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin inducing T cell anergy

Rodríguez

Kalay

Noya

et al. 2017

Sci Rep

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“…However, little is known about the type of DCs responsible for inducing Tfh cell priming. A recent study reported that engagement of DC-SIGN by fucose-based PAMPs licenses DCs for inducing Tfh polarization (17). Such activated DCs produce IL-27, which is essential for Tfh polarization.…”

Section: Potential Impact Of Hiv Infection On Tfh Cell Differentiationmentioning

confidence: 99%

Impact of Chronic HIV/SIV Infection on T Follicular Helper Cell Subsets and Germinal Center Homeostasis

2016

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The discovery of broad and potent HIV-1 neutralizing antibodies (bNAbs) has renewed optimism for developing an effective vaccine against HIV-1. The generation of most bNAbs requires multiple rounds of B cell receptor affinity maturation, suggesting a crucial role of follicular helper T (Tfh) cells in their production. However, less than 1% of HIV-infected patients develop bNAbs that arise late in the course of infection, indicating probable Tfh and B cell dysfunctions in this context. Since the last few years, many studies have characterized Tfh cells from lymph nodes and spleen of HIV-infected individuals and SIV-infected macaques. Various lymphoid Tfh cell subsets have been identified, including precursor Tfh (pTfh), germinal center Tfh (GC Tfh), and the regulatory counterpart of Tfh cells, the follicular regulatory T cells. The latter have been reported to play a crucial role in the control of T and B cell crosstalk and GC reactions. More recently, circulating Tfh-like cells (cTfh) have been identified. Meanwhile, advances in single-cell technologies have made possible to analyze the transcriptional profiles of low abundant cells, such as Tfh populations. Using transcriptional signatures, we review here the impact of chronic SIV/HIV infection on Tfh, GC Tfh, pTfh, and cTfh differentiation and helper T cell functions with regard to their capacity to induce efficient B cell maturation. We will explore some hypothesis to explain the increased proportion of Tfh cells reported in chronically infected individuals and the impact on HIV pathogenesis.

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“…Further interactions between DC and/or B cells and transitional Tfh cells at the follicle borders, and then B cells with Tfh cells within the developing germinal centers (GCs), are thought to solidify and amplify the Tfh differentiation program leading to pools of mature or GC Tfh cells that control the GC B cell response. Several molecules have been demonstrated to control Tfh and GC Tfh development, including the cytokines IL-6, IL-27 (8), IL-21 (9), transcription factors STAT3 (10) and STAT4 (11), and membrane interactions between CD28/B7 (12) and ICOS/ICOSL (13, 14). However, other molecular interactions that may be required for the maintenance or amplification of the Tfh program are still not clear.…”

Section: Introductionmentioning

confidence: 99%

OX40 Cooperates with ICOS To Amplify Follicular Th Cell Development and Germinal Center Reactions during Infection

Tahiliani

Hutchinson

Abboud

et al. 2017

The Journal of Immunology

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Cognate interactions between T-follicular helper cells (Tfh) and B cells are essential for promoting protective antibody responses. Whereas costimulatory receptors like ICOS are accepted as being important for the induction of Tfh cell fate decision, other molecules may play key roles in amplifying or maintaining the Tfh phenotype. Here, with vaccinia virus infection in mice, we show that OX40 was expressed on Tfh cells that accumulated at the T:B borders in the white pulp of the spleen and that OX40-dependent signals directly shaped the magnitude and quality of the their response to viral antigens. OX40 deficiency in Tfh cells profoundly impaired the acquisition of germinal center (GC) B cell phenotype, plasma cell generation, and virus-specific Ab responses. Most significantly, we found that sustained interactions between OX40 and its ligand, OX40L, beyond the time of initial encounter with dendritic cells were required for the persistence of high numbers of Tfh and GC B cells. Interestingly, OX40 was co-expressed with ICOS on Tfh cells in and around the GC, and ICOS-ICOSL interactions were similarly crucial at late times for maintenance of the Tfh and GC B cells. Thus, OX40 and ICOS act in a cooperative, nonredundant manner to maximize and prolong the Tfh response that is generated after acute virus infection.

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Fucose-based PAMPs prime dendritic cells for follicular T helper cell polarization via DC-SIGN-dependent IL-27 production

Cited by 86 publications

References 52 publications

Fasciola hepatica glycoconjugates immuneregulate dendritic cells through the Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin inducing T cell anergy

Fasciola hepatica glycoconjugates immuneregulate dendritic cells through the Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin inducing T cell anergy

Impact of Chronic HIV/SIV Infection on T Follicular Helper Cell Subsets and Germinal Center Homeostasis

OX40 Cooperates with ICOS To Amplify Follicular Th Cell Development and Germinal Center Reactions during Infection

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