DC-SIGN Interactions with Human Immunodeficiency Virus Type 1 and 2 and Simian Immunodeficiency Virus

Pöhlmann, Stefan; Baribaud, Frédéric; Lee, Benhur; Leslie, George J.; Sánchez, Melissa D.; Hiebenthal-Millow, Kirsten; Münch, Jan; Kirchhoff, Frank; Doms, Robert W.

doi:10.1128/jvi.75.10.4664-4672.2001

Cited by 209 publications

(235 citation statements)

References 33 publications

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“…Until now, the only antigenic ligands known to bind DC-SIGN are lentiviruses, including HIV-1, HIV-2, and SIV-2 (26,44). We have recently shown that DCs efficiently capture HIV-1 through a highaffinity interaction of gp120 with DC-SIGN and mediate subsequent transmission of HIV-1 to T cells (26).…”

Section: Ags That Target To Dc-signmentioning

confidence: 99%

The Dendritic Cell-Specific Adhesion Receptor DC-SIGN Internalizes Antigen for Presentation to T Cells

Engering¹,

Geijtenbeek²,

Vliet³

et al. 2002

The Journal of Immunology

569

500

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Dendritic cells (DCs) capture Ags or viruses in peripheral tissue to transport them to lymphoid organs to induce cellular T cell responses. Recently, a DC-specific C-type lectin was identified, DC-specific ICAM-grabbing non-integrin (DC-SIGN), that functions as cell adhesion receptor mediating both DC migration and T cell activation. DC-SIGN also functions as an HIV-1R that captures HIVgp120 and facilitates DC-induced HIV transmission of T cells. Internalization motifs in the cytoplasmic tail of DC-SIGN hint to a function of DC-SIGN as endocytic receptor. In this study we demonstrate that on DCs DC-SIGN is rapidly internalized upon binding of soluble ligand. Mutating a putative internalization motif in the cytoplasmic tail reduces ligand-induced internalization. Detailed analysis using ratio fluorescence imaging and electron microscopy showed that DC-SIGN-ligand complexes are targeted to late endosomes/lysosomes. Moreover, ligands internalized by DC-SIGN are efficiently processed and presented to CD4+ T cells. The distinct pattern of expression of C-type lectins on DCs in situ and their nonoverlapping Ag recognition profile hint to selective functions of these receptors to allow a DC to recognize a wide variety of Ags and to process these to induce T cell activation. These data point to a novel function of the adhesion receptor DC-SIGN as an efficient DC-specific Ag receptor that can be used as a target to induce viral and antitumor immunity.

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Section: Ags That Target To Dc-signmentioning

confidence: 99%

The Dendritic Cell-Specific Adhesion Receptor DC-SIGN Internalizes Antigen for Presentation to T Cells

Engering¹,

Geijtenbeek²,

Vliet³

et al. 2002

The Journal of Immunology

569

500

View full text Add to dashboard Cite

show abstract

“…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%

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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“…Peripheral blood mononuclear cells (PBMC) of rhesus macaque (Macaca mulatta) were Ficoll gradient-purified from peripheral blood and cultured in the presence of 500 units͞ml IL-4 and 800 units͞ml granulocytemacrophage colony-stimulating factor (R & D Systems). Total RNA was isolated from the cultured cells with Trizol (Life Technologies, Grand Island, NY), primed with oligo(dT) [12][13][14][15][16][17][18] , and transcribed by using Superscript II reverse transcriptase (Life Technologies) according to the manufacturer's protocol. mac-DC-SIGN cDNA was amplified with the following primers: dc-sign1, 5Ј-AGT GGG GTG ACA TGA GTG AC-3Ј and s-9m, 5Ј-GAA GTT CTG CTA CTC AGG AG-3Ј.…”

Section: Methodsmentioning

confidence: 99%

“…Indeed, expression of DC-SIGN on monocytic cell lines conferred the cells with an ability to bind and efficiently transmit HIV-1 in a manner that was completely dependent on direct interactions between DC-SIGN and HIV-1 Env (11). Beyond a requirement for direct interaction between HIV-1 Env and the carbohydrate recognition domain of DC-SIGN for virus transmission function (17), little is currently known about the mechanism of transmission to target cells bearing HIV-1 receptors. Furthermore, it has not been determined whether DC-SIGN contributes to viral pathogenesis by (i) facilitating mucosal transmission of HIV͞SIV through resident, patrolling immature DC or (ii) catalyzing sustained HIV͞SIV replication in lymphoid tissue by mature DC.…”

mentioning

confidence: 99%

Rhesus macaque dendritic cells efficiently transmit primate lentiviruses independently of DC-SIGN

Bashirova

Martin

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Here, we describe the isolation and characterization of the rhesus macaque homolog for human DC-SIGN, a dendritic cell-specific C-type lectin. mac-DC-SIGN is 92% identical to hu-DC-SIGN. mac-DC-SIGN preserves the virus transmission function of hu-DC-SIGN, capturing and efficiently transducing simian and human immunodeficiency virus to target CD4 ؉ T cells. Surprisingly, however, mac-DC-SIGN plays no discernable role in the ability of rhesus macaque dendritic cells to capture and transmit primate lentiviruses. Expression and neutralization analyses suggest that this process is DC-SIGN independent in macaque, although the participation of other lectin molecules cannot be ruled out. The ability of primate lentiviruses to effectively use human and rhesus dendritic cells in virus transmission without the cells becoming directly infected suggests that these viruses have taken advantage of a conserved dendritic cell mechanism in which DC-SIGN family molecules are significant contributors but not the only participants.

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DC-SIGN Interactions with Human Immunodeficiency Virus Type 1 and 2 and Simian Immunodeficiency Virus

Cited by 209 publications

References 33 publications

The Dendritic Cell-Specific Adhesion Receptor DC-SIGN Internalizes Antigen for Presentation to T Cells

The Dendritic Cell-Specific Adhesion Receptor DC-SIGN Internalizes Antigen for Presentation to T Cells

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

Rhesus macaque dendritic cells efficiently transmit primate lentiviruses independently of DC-SIGN

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