Mycobacteria Target DC-SIGN to Suppress Dendritic Cell Function

Geijtenbeek, Teunis B. H.; Vliet, Sandra J. van; Koppel, Estella A; Sánchez-Hernández, Marta; Vandenbroucke-Grauls, Christina M. J. E.; Appelmelk, Ben J.; Kooyk, Yvette van

doi:10.1084/jem.20021229

Cited by 950 publications

(910 citation statements)

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“…Interestingly, blocking of the interaction between DC and T cells with an anti-DC-SIGN antibody influences allostimulatory properties in T cells [1]. Several recent studies have demonstrated that cross-talk between C-type lectins and TLR can occur [14,32,33], suggesting that simultaneous interaction of pathogens with both receptors can modulate the response by DC. In this context, a recent study indicates that activation of DC by HPV L1-VLP is MyD88 dependent [34].…”

Section: Blocking the Interaction Of L1-vlp With Dc-sign Inhibits Vlpmentioning

confidence: 99%

“…In addition to HIV, DC-SIGN was recently shown to bind a variety of microorganisms such as CMV [4], Ebola virus [5], Dengue virus [6], hepatitis C virus [7,8], simian immunodeficiency virus [9], Leishmania [10], Candida albicans [11], Mycobacterium [12][13][14] and Schistosoma [15]. Some pathogens subvert DC functions to escape immune surveillance [16].…”

Section: Introductionmentioning

confidence: 99%

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Role of DC‐SIGN in the activation of dendritic cells by HPV‐16 L1 virus‐like particle vaccine

et al. 2006

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Dendritic cell-specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN), a specific C-type lectin expressed on DC, binds and transmits different pathogens to susceptible cells. In the present study, we examined the role of DC-SIGN in the capture of human papillomavirus (HPV) pseudovirions and activation of DC. We demonstrate that HPV virus-like particles (VLP) bind to DC-SIGN expressed on transfected Raji cells and that antibodies against DC-SIGN block this interaction. DC take up VLP, which activate expression of costimulatory markers and cytokines/ chemokines. Although our results indicate that DC-SIGN is not the major receptor for VLP in DC, this interaction contributes to the activation of DC surface antigens (HLA class I) and of various cytokines/chemokines, particularly TNF-a, IL-6, and RANTES. Induction of these markers in DC by VLP was significantly abrogated when binding to DC-SIGN was blocked by anti-DC-SIGN antibodies. These results suggest that DC-SIGN has a functional role in DC activation induced by HPV-16 L1-VLP, and thus highlight new aspects of DC interactions with HPV VLP. IntroductionThe C-type lectin dendritic cell-specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN; CD209) is a pathogen recognition receptor that interacts with mannose residues of glycoproteins in a calciumdependent manner via its C-terminal carbohydrate recognition domain [1,2]. DC-SIGN acts both as an adhesion molecule and pathogen recognition receptor, facilitating DC binding and internalization of several viruses, including HIV-1 [3].In addition to HIV, DC-SIGN was recently shown to bind a variety of microorganisms such as CMV [4], Ebola virus [5], Dengue virus [6], hepatitis C virus [7,8], simian immunodeficiency virus [9], Leishmania [10], Candida albicans [11], Mycobacterium [12][13][14] and Schistosoma [15]. Some pathogens subvert DC functions to escape immune surveillance [16]. DC-SIGN is abundantly expressed primarily on DC, including those derived from monocytes and those located beneath the genital surface [3].Human papillomavirus (HPV) virus-like particles (VLP) are a promising vaccine candidate for HPV and cervical cancer [17][18][19][20]. Recent clinical trials have shown that VLP afford excellent protection against persistent infection [20,21]. Because of the lack of a suitable cell culture system for in vitro propagation of HPV and the unavailability of virions, HPV VLP have been used as soluble surrogates for native virus particles. The routes of HPV-16 L1-VLP entry in DC and the nature of cellular receptors involved in capture have been studied but remain to be fully characterized. HPV VLP Here, we report that HPV-16 L1-VLP particles bind to DC-SIGN in transfected cell lines, and to a lesser extent in DC, and that this interaction participates in L1-VLPinduced activation of DC. Thus, DC-SIGN is likely involved in DC activation by HPV VLP. Results and discussion HPV L1-VLP bind to DC-SIGN in DC-SIGN-transfected cell linesTo study interactions between L1-VLP and DC-SIGN, we...

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Section: Blocking the Interaction Of L1-vlp With Dc-sign Inhibits Vlpmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Role of DC‐SIGN in the activation of dendritic cells by HPV‐16 L1 virus‐like particle vaccine

et al. 2006

View full text Add to dashboard Cite

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“…It is known that DC interact with yeasts essentially by the mannose-binding receptors CD206 [22,31] 32,[34][35][36][37] and TLR2 [32,38,39]. Therefore, we analyzed Candida uptake in the presence of mannan, which binds both CD206 and DC-SIGN [40,41] and interferes with particle internalization by these receptors [42], or laminarin, a specific dectin-1 inhibitor [27,35,40,41,43]. Fig.…”

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confidence: 99%

NADPH oxidase of human dendritic cells: Role in Candida albicans killing and regulation by interferons, dectin‐1 and CD206

et al. 2007

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Human monocyte-derived DC express the enzyme NADPH oxidase, responsible for ROS production. We show that Candida albicans did not activate NADPH oxidase in DC, and was poorly killed by these cells. However, Candida-killing activity increased upon DC stimulation with the NADPH oxidase activator PMA and was further enhanced by DC treatment with IFN-a or IFN-c. This fungicidal activity took place at high DC-to-Candida ratio, but decreased at low DC-to-yeast ratio, when Candida inhibited the NADPH oxidase by contrasting the assembly of the enzyme on DC plasma membrane. The NADPH oxidase inhibitor diphenyliodonium chloride abrogated the PMA-dependent DC candidacidal capacity. Engagement of b-glucan receptor dectin-1 induced NADPH oxidase activation in DC that was depressed by mannose-binding receptor CD206 costimulation. Candida was internalized by DC through mannose-binding receptors, but not through dectin-1, thus explaining why Candida did not elicit NADPH oxidase activity. Our results indicate that NADPH oxidase is involved in DC Candida-killing activity, which is increased by IFN. However, Candida escapes the oxidative damage by inhibiting NADPH oxidase and by entering DC through receptors not involved in NADPH oxidase activation. IntroductionDendritic cells (DC) play an important role in the initiation of immune responses [1][2][3][4]. In peripheral tissues, immature DC capture antigens by specialized receptors, undergo maturation and migrate to lymphoid organs where they present antigens to naive T cells [1][2][3][4]. Moreover, DC produce cytotoxic molecules limiting pathogen replication [5][6][7][8].Recently, we reported that human monocyte-derived DC express NADPH oxidase [9], the enzyme of leukocytes responsible for ROS production, whose activation requires the association between cytosolic (p47phox, p67phox, p40phox, p21rac) and membrane (gp91phox, p22phox) components [10,11]. ROS produced by NADPH oxidase of leukocytes are involved in pathogen killing, as demonstrated by the recurrent infections affecting individuals with chronic granulomatous disease, an inherited disorder in which the enzyme is not functional [10,11], but are also recognized as signaling molecules [12]. We previously showed that NADPH oxidase is not involved in DC differentiation, LPS-induced maturation, cytokine production and induction of T cell proliferation, but is required for DC killing of intracellular bacteria [9].The present study was undertaken to elucidate in more detail the regulation of DC NADPH oxidase activity and the role of this enzyme in pathogen-killing ability of ResultsRegulation of NADPH oxidase activity by IFN-a and IFN-cWe previously reported that PMA-stimulated human monocyte-derived DC release superoxide anion, which was nearly completely produced via NADPH oxidase activation [9]. Here we show that immature DC treatment with IFN-a or IFN-c enhanced the PMA-induced NADPH oxidase activity (Fig.1A, B). A surface phenotype analysis by flow cytometry demonstrated that this effect was not consequent to changes of DC...

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“…[81] and [82] Most recently, Schlesinger and Torrelles have demonstrated that M. tuberculosis clinical isolates vary in their degree of surface mannosylation and they suggest these differences may have great impact on the outcome of the disease.78 There is direct evidence manLAM affects DC maturation and function [79], [83] and [84] and the same antigen either as a cell wall component of M. tuberculosis or as a free antigen, drives DCs into IL-10 production. [76], [85], [86], [87], [88] The role of cell death in the immune response to M. tuberculosis M. tuberculosis is an intracellular pathogen and its survival within the host requires living cells. Cell suicide is an important innate defence against intracellular pathogens.…”

Section: Role Of Mycobacterial Antigens In Persistence Of M Tuberculmentioning

confidence: 99%

Optimization of inhaled therapies for tuberculosis: The role of macrophages and dendritic cells

González-Juarrero

O’Sullivan

2011

Tuberculosis

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SummaryInhaled therapies in the form of drugs or vaccines for tuberculosis treatment were reported about a decade ago. Experts around the world met to discuss the scientific progress in inhaled therapies at the international symposium "Optimization of inhaled Tuberculosis therapies and implications for host-pathogen interactions" held in New Delhi, India on November 3-5, 2009. The meeting was organized by the Central Drug Research Institute (CDRI) Lucknow, India. The lung is the main route for infection with Mycobacterium tuberculosis bacilli and the primary site of reactivation of latent disease. The only available vaccine BCG is relatively ineffective at preventing tuberculosis disease and current therapy requires prolonged treatment with drugs which results in low patient compliance. Consequently, there is a need to design new vaccines and therapies for this disease. Recently there has been increased interest in the development of inhaled formulations to deliver anti-mycobacterial drugs and vaccines directly to the lung and many of these therapies are designed to target lung macrophages and dendritic cells. However, the development of effective inhaled therapies requires an understanding of the unique function and immunosuppressive environment of the lung which is driven, in part, by alveolar macrophages and dendritic cells. In this review, we will discuss the role of alveolar macrophages and dendritic cells in the host immune response to M. tuberculosis infection and the ways in which inhaled therapies might enhance the anti-microbial response of phagocytes and boost pulmonary immunity.Keywords: Tuberculosis; Macrophage; Dendritic cell; Inhaled therapy stimulate innate bactericidal responses and/or antigen presenting functions more efficiently and will ameliorate drug toxicity due to reduction in dose/duration of treatment.12 However, the development of successful inhaled therapies in general will depend on the confounding characteristics of the lungs, in addition to the multiple variables added by alterations in its structure and damage inflicted by the inflammatory process, and needs to take into account factors such as aeration of the lungs, deposition and lung function, formation of biofilms and resistance in the face of treatment. [12] and [13]

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Mycobacteria Target DC-SIGN to Suppress Dendritic Cell Function

Cited by 950 publications

References 41 publications

Role of DC‐SIGN in the activation of dendritic cells by HPV‐16 L1 virus‐like particle vaccine

Role of DC‐SIGN in the activation of dendritic cells by HPV‐16 L1 virus‐like particle vaccine

NADPH oxidase of human dendritic cells: Role in Candida albicans killing and regulation by interferons, dectin‐1 and CD206

Optimization of inhaled therapies for tuberculosis: The role of macrophages and dendritic cells

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