HIV gp120 receptors on human dendritic cells

Blood ◽  
2001 ◽  
Vol 98 (8) ◽  
pp. 2482-2488 ◽  
Author(s):  
Stuart G. Turville ◽  
Jim Arthos ◽  
Kelli Mac Donald ◽  
Garry Lynch ◽  
Hassan Naif ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Ex Vivo ◽  
Mannose Receptor ◽  
Lectin Receptor ◽  
Immunodeficiency Virus ◽  
Processing Pathways ◽  
Human Dendritic Cells ◽  
Hiv Gp120 ◽  
Hiv Envelope ◽  
Transfer Mechanisms

Abstract Dendritic cells (DCs) are important targets for human immunodeficiency virus (HIV) because of their roles during transmission and also maintenance of immune competence. Furthermore, DCs are a key cell in the development of HIV vaccines. In both these settings the mechanism of binding of the HIV envelope protein gp120 to DCs is of importance. Recently a single C-type lectin receptor (CLR), DC-SIGN, has been reported to be the predominant receptor on monocyte-derived DCs (MDDCs) rather than CD4. In this study a novel biotinylated gp120 assay was used to determine whether CLR or CD4 were predominant receptors on MDDCs and ex vivo blood DCs. CLR bound more than 80% of gp120 on MDDCs, with residual binding attributable to CD4, reconfirming that CLRs were the major receptors for gp120 on MDDCs. However, in contrast to recent reports, gp120 binding to at least 3 CLRs was observed: DC-SIGN, mannose receptor, and unidentified trypsin resistant CLR(s). In marked contrast, freshly isolated and cultured CD11c+ve and CD11c−ve blood DCs only bound gp120 via CD4. In view of these marked differences between MDDCs and blood DCs, HIV capture by DCs and transfer mechanisms to T cells as well as potential antigenic processing pathways will need to be determined for each DC phenotype.

scholarly journals A single immunization with CAF08 provides newborns with Th1-mediated protection against Respiratory Syncytial Virus infection

2021 ◽  
Author(s):  
Simon van Haren ◽  
Gabriel Kristian Pedersen ◽  
Azad Kumar ◽  
Tracy Ruckwardt ◽  
Syed Moin ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Respiratory Syncytial Virus ◽  
Early Life ◽  
T Helper 1 ◽  
Newborn Mice ◽  
Cross Presentation ◽  
Lectin Receptor ◽  
Syncytial Virus ◽  
Human Dendritic Cells

Abstract Respiratory Syncytial Virus (RSV) is a leading cause of morbidity and mortality in children, due in part to their distinct immune system, characterized by impaired induction of T-helper 1 (Th1)-immunity. Here we describe cationic adjuvant formulation (CAF)-08, a liposomal vaccine formulation tailored to induce Th1 immunity in early life via synergistic engagement of Toll-like Receptor 7/8 and the C-type lectin receptor Mincle. Quantitative phosphoproteomics applied to human dendritic cells revealed a key role for Protein Kinase C-δ for enhanced Th1 cytokine production in neonatal dendritic cells and identified signaling events resulting in antigen cross-presentation. In vivo, a single immunization at birth with CAF08-adjuvanted RSV pre-fusion antigen protected newborn mice from RSV infection through induction of antigen-specific CD8+ and Th1 cells. Overall, we describe a novel pediatric adjuvant formulation and characterize its mechanism of action providing a promising avenue for development of early life vaccines against RSV and other intracellular pathogens.

The mannose receptor functions as a high capacity and broad specificity antigen receptor in human dendritic cells

1997 ◽  
Vol 27 (9) ◽  
pp. 2417-2425 ◽  
Author(s):  
Anneke J. Engering ◽  
Marina Cella ◽  
Donna Fluitsma ◽  
Manfred Brockhaus ◽  
Elizabeth C. M. Hoefsmit ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
High Capacity ◽  
Antigen Receptor ◽  
Mannose Receptor ◽  
Human Dendritic Cells ◽  
Broad Specificity

scholarly journals Internalization and endosomal degradation of receptor-bound antigens regulate the efficiency of cross presentation by human dendritic cells

Blood ◽  
2012 ◽  
Vol 120 (10) ◽  
pp. 2011-2020 ◽  
Author(s):  
Bithi Chatterjee ◽  
Anna Smed-Sörensen ◽  
Lillian Cohn ◽  
Cécile Chalouni ◽  
Richard Vandlen ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Vaccine Development ◽  
Mannose Receptor ◽  
Antigen Delivery ◽  
Cross Presentation ◽  
Late Endosomes ◽  
Early Endosomes ◽  
Antibody Conjugates ◽  
Human Dendritic Cells ◽  
Endocytic Compartments

Abstract Dendritic cells (DCs) can capture extracellular antigens and load resultant peptides on to MHC class I molecules, a process termed cross presentation. The mechanisms of cross presentation remain incompletely understood, particularly in primary human DCs. One unknown is the extent to which antigen delivery to distinct endocytic compartments determines cross presentation efficiency, possibly by influencing antigen egress to the cytosol. We addressed the problem directly and quantitatively by comparing the cross presentation of identical antigens conjugated with antibodies against different DC receptors that are targeted to early or late endosomes at distinct efficiencies. In human BDCA1+ and monocyte-derived DCs, CD40 and mannose receptor targeted antibody conjugates to early endosomes, whereas DEC205 targeted antigen primarily to late compartments. Surprisingly, the receptor least efficient at internalization, CD40, was the most efficient at cross presentation. This did not reflect DC activation by CD40, but rather its relatively poor uptake or intra-endosomal degradation compared with mannose receptor or DEC205. Thus, although both early and late endosomes appear to support cross presentation in human DCs, internalization efficiency, especially to late compartments, may be a negative predictor of activity when selecting receptors for vaccine development.

Involvement of the mannose receptor in the uptake of der p 1, a major mite allergen, by human dendritic cells

2002 ◽  
Vol 110 (5) ◽  
pp. 763-770 ◽  
Author(s):  
Gaë tan Deslée ◽  
Anne-Sophie Charbonnier ◽  
Hamida Hammad ◽  
Gerhild Angyalosi ◽  
Isabelle Tillie-Leblond ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Mannose Receptor ◽  
Mite Allergen ◽  
Der P 1 ◽  
Human Dendritic Cells

scholarly journals DC-SIGN Is the Major Mycobacterium tuberculosis Receptor on Human Dendritic Cells

2002 ◽  
Vol 197 (1) ◽  
pp. 121-127 ◽  
Author(s):  
Ludovic Tailleux ◽  
Olivier Schwartz ◽  
Jean-Louis Herrmann ◽  
Elisabeth Pivert ◽  
Mary Jackson ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Mycobacterium Tuberculosis ◽  
Human Monocyte ◽  
Mannose Receptor ◽  
Intercellular Adhesion Molecule ◽  
Minor Role ◽  
Hla Dr ◽  
A Minor ◽  
Human Dendritic Cells

Early interactions between lung dendritic cells (LDCs) and Mycobacterium tuberculosis, the etiological agent of tuberculosis, are thought to be critical for mounting a protective anti-mycobacterial immune response and for determining the outcome of infection. However, these interactions are poorly understood, at least at the molecular level. Here we show that M. tuberculosis enters human monocyte-derived DCs after binding to the recently identified lectin DC-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN). By contrast, complement receptor (CR)3 and mannose receptor (MR), which are the main M. tuberculosis receptors on macrophages (Mϕs), appeared to play a minor role, if any, in mycobacterial binding to DCs. The mycobacteria-specific lipoglycan lipoarabinomannan (LAM) was identified as a key ligand of DC-SIGN. Freshly isolated human LDCs were found to express DC-SIGN, and M. tuberculosis–derived material was detected in CD14−HLA-DR+DC-SIGN+ cells in lymph nodes (LNs) from patients with tuberculosis. Thus, as for human immunodeficiency virus (HIV), which is captured by the same receptor, DC-SIGN–mediated entry of M. tuberculosis in DCs in vivo is likely to influence bacterial persistence and host immunity.

scholarly journals Human dendritic cells shed a functional, soluble form of the mannose receptor

1999 ◽  
Vol 11 (11) ◽  
pp. 1775-1780 ◽  
Author(s):  
Reina Jordens ◽  
Allan Thompson ◽  
Reinout Amons ◽  
Frits Koning
Keyword(s):  
Dendritic Cells ◽  
Mannose Receptor ◽  
Soluble Form ◽  
Human Dendritic Cells

scholarly journals Binding and Transfer of Human Immunodeficiency Virus by DC-SIGN+ Cells in Human Rectal Mucosa

2005 ◽  
Vol 79 (9) ◽  
pp. 5762-5773 ◽  
Author(s):  
Kevin B. Gurney ◽  
Julie Elliott ◽  
Hoorig Nassanian ◽  
Carol Song ◽  
Elizabeth Soilleux ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dendritic Cells ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Rectal Mucosa ◽  
Virus Binding ◽  
Mucosal Transmission ◽  
Hla Dr ◽  
Immunodeficiency Virus

ABSTRACT The role of DC-SIGN on human rectal mucosal dendritic cells is unknown. Using highly purified human rectal mucosal DC-SIGN+ cells and an ultrasensitive real-time reverse transcription-PCR assay to quantify virus binding, we found that HLA-DR+/DC-SIGN+ cells can bind and transfer more virus than the HLA-DR+/DC-SIGN− cells. Greater than 90% of the virus bound to total mucosal mononuclear cells (MMCs) was accounted for by the DC-SIGN+ cells, which comprise only 1 to 5% of total MMCs. Significantly, anti-DC-SIGN antibodies blocked 90% of the virus binding when more-physiologic amounts of virus inoculum were used. DC-SIGN expression in the rectal mucosa was significantly correlated with the interleukin-10 (IL-10)/IL-12 ratio (r = 0.58, P < 0.002; n = 26) among human immunodeficiency virus (HIV)-positive patients. Ex vivo and in vitro data implicate the role of IL-10 in upregulating DC-SIGN expression and downregulating expression of the costimulatory molecules CD80/CD86. Dendritic cells derived from monocytes (MDDCs) in the presence of IL-10 render the MDDCs less responsive to maturation stimuli, such as lipopolysaccharide and tumor necrosis factor alpha, and migration to the CCR7 ligand macrophage inflammatory protein 3β. Thus, an increased IL-10 environment could render DC-SIGN+ cells less immunostimulatory and migratory, thereby dampening an effective immune response. DC-SIGN and the IL-10/IL-12 axis may play significant roles in the mucosal transmission and pathogenesis of HIV type 1.

scholarly journals Hepatitis C Virus Glycoproteins Interact with DC-SIGN and DC-SIGNR

2003 ◽  
Vol 77 (7) ◽  
pp. 4070-4080 ◽  
Author(s):  
Stefan Pöhlmann ◽  
Jie Zhang ◽  
Frédéric Baribaud ◽  
Zhiwei Chen ◽  
George J. Leslie ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Dendritic Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Cell Function ◽  
Human Monocyte ◽  
Surface Molecules ◽  
E2 Glycoprotein ◽  
Immunodeficiency Virus ◽  
Hiv Envelope

ABSTRACT DC-SIGN and DC-SIGNR are two closely related membrane-associated C-type lectins that bind human immunodeficiency virus (HIV) envelope glycoprotein with high affinity. Binding of HIV to cells expressing DC-SIGN or DC-SIGNR can enhance the efficiency of infection of cells coexpressing the specific HIV receptors. DC-SIGN is expressed on some dendritic cells, while DC-SIGNR is localized to certain endothelial cell populations, including hepatic sinusoidal endothelial cells. We found that soluble versions of the hepatitis C virus (HCV) E2 glycoprotein and retrovirus pseudotypes expressing chimeric forms of both HCV E1 and E2 glycoproteins bound efficiently to DC-SIGN and DC-SIGNR expressed on cell lines and primary human endothelial cells but not to other C-type lectins tested. Soluble E2 bound to immature and mature human monocyte-derived dendritic cells (MDDCs). Binding of E2 to immature MDDCs was dependent on DC-SIGN interactions, while binding to mature MDDCs was partly independent of DC-SIGN, suggesting that other cell surface molecules may mediate HCV glycoprotein interactions. HCV interactions with DC-SIGN and DC-SIGNR may contribute to the establishment or persistence of infection both by the capture and delivery of virus to the liver and by modulating dendritic cell function.

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