scholarly journals Human dendritic cell sequestration onto the Necator americanus larval sheath during ex-sheathing: a possible mechanism for immune privilege

Parasitology ◽  
2018 ◽  
Vol 145 (9) ◽  
pp. 1183-1190 ◽  
Author(s):  
A. Hassan ◽  
D. I. Pritchard ◽  
A. M. Ghaemmaghami
Keyword(s):  
Dendritic Cells ◽  
Mannose Receptor ◽  
Host Immune System ◽  
Immune Recognition ◽  
Human Dendritic Cell ◽  
Lectin Receptors ◽  
Necator Americanus ◽  
Initial Interaction ◽  
Human Dendritic Cells ◽  
Low Expression

AbstractDespite the profound health implications of Necator americanus infection in humans, many aspects of its interaction with the host immune system are poorly understood. Here we investigated the early events at the interface of N. americanus larvae (L3) and human dendritic cells (DCs). Our data show that co-culturing DCs and the larvae trigger ex-sheathing of hookworms rapidly where a majority of DCs are sequestered onto the larval sheath allowing the ex-sheathed larvae to migrate away unchallenged. Intriguingly, DCs show negligible interaction with the ex-sheathed larvae, alluding to differences between the surface chemistry of the larva and its sheath. Furthermore, blocking of two key C-type lectin receptors on DC surface (i.e. DC-SIGN and mannose receptor) resulted in inhibition of ex-sheathing process and DC sequestration, highlighting the importance of C-type lectins on DCs in the induction of the ex-sheathing. Analyses of DC phenotype and cytokine profile after co-culture with the N. americanus larvae showed an immature phenotype as evidenced by the low expression of the maturation markers and cytokines. These data provide new insights into early events at the interface of human DCs and N. americanus larvae and could explain how L3 evade immune recognition upon initial interaction with DCs.

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.

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 The macrophage mannose receptor promotes uptake of ADAMTS13 by dendritic cells

Blood ◽  
2012 ◽  
Vol 119 (16) ◽  
pp. 3828-3835 ◽  
Author(s):  
Nicoletta Sorvillo ◽  
Wouter Pos ◽  
Linda M. van den Berg ◽  
Rob Fijnheer ◽  
Luisa Martinez-Pomares ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Mhc Class Ii ◽  
Cd4 T Cells ◽  
Mannose Receptor ◽  
Immune Recognition ◽  
Binding Studies ◽  
Macrophage Mannose Receptor ◽  
Carbohydrate Recognition Domains

Abstract ADAMTS13 is a plasma metalloproteinase that regulates platelet adhesion and aggregation by cleaving ultra-large VWF multimers on the surfaces of endothelial cells. Autoantibodies directed against ADAMTS13 prohibit the processing of VWF multimers, initiating a rare and life-threatening disorder called acquired thrombotic thrombocytopenic purpura. The formation of autoantibodies depends on the activation of CD4+ T cells. This process requires immune recognition, endocytosis, and subsequent processing of ADAMTS13 into peptides that are presented on MHC class II molecules to CD4+ T cells by dendritic cells (DCs). In the present study, we investigated endocytosis of recombinant ADAMTS13 by immature monocyte-derived DCs using flow cytometry and confocal microscopy. After incubation of fluorescently labeled ADAMTS13 with DCs, significant uptake of ADAMTS13 was observed. Endocytosis of ADAMTS13 was completely blocked by the addition of EGTA and mannan. ADAMTS13 endocytosis was decreased in the presence of a blocking mAb directed toward the macrophage mannose receptor (MR). Furthermore, siRNA silencing of MR reduced the uptake of ADAMTS13 by DCs. In addition, in vitro binding studies confirmed the interaction of ADAMTS13 with the carbohydrate recognition domains of MR. The results of the present study indicate that sugar moieties on ADAMTS13 interact with MR, thereby promoting its endocytosis by APCs.

Synthesis and mannose receptor-Mediated uptake of clustered glycomimetics by human dendritic cells: effect of charge

2002 ◽  
Vol 12 (19) ◽  
pp. 2723-2727 ◽  
Author(s):  
Gerhild Angyalosi ◽  
Cyrille Grandjean ◽  
Mélanie Lamirand ◽  
Claude Auriault ◽  
Hélène Gras-Masse ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Mannose Receptor ◽  
Human Dendritic Cells

Targeting DCIR on human plasmacytoid dendritic cells results in antigen presentation and inhibits IFN-α production

Blood ◽  
2008 ◽  
Vol 111 (8) ◽  
pp. 4245-4253 ◽  
Author(s):  
Friederike Meyer-Wentrup ◽  
Daniel Benitez-Ribas ◽  
Paul J. Tacken ◽  
Cornelis J. A. Punt ◽  
Carl G. Figdor ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Antigen Presentation ◽  
Costimulatory Molecule ◽  
Mannose Receptor ◽  
Dominant Negative ◽  
Major Type ◽  
Type I ◽  
Myeloid Dendritic Cells ◽  
Lectin Receptors ◽  
Inhibitory Function

Abstract C-type lectin receptors (CLRs) fulfill multiple functions within the immune system by recognition of carbohydrate moieties on foreign or (altered) self-structures. CLRs on myeloid dendritic cells (DCs) have been well characterized as pattern-recognition receptors (PRRs) combining ligand internalization with complex signaling events. Much less is known about CLR expression and function in human plasmacytoid DCs (pDCs), the major type I interferon (IFN) producers. In this study, we demonstrate that, next to the CLR BDCA-2, human pDCs express DC immunoreceptor (DCIR), a CLR with putative immune-inhibitory function, but not dectin-1, mannose receptor, or DC-specific ICAM-3–grabbing nonintegrin. DCIR surface levels are reduced on pDC maturation after TLR9 triggering. Interestingly, DCIR triggering inhibits TLR9-induced IFN-α production while leaving up-regulation of costimulatory molecule expression unaffected. Furthermore, DCIR is readily internalized into pDCs after receptor triggering. We show that DCIR internalization is clathrin-dependent because it can be inhibited by hypertonic shock and dominant-negative dynamin. Importantly, antigens targeted to pDCs via DCIR are presented to T cells. These findings indicate that targeting DCIR on pDCs not only results in efficient antigen presentation but also affects TLR9-induced IFN-α production. Collectively, the data show that targeting of DCIR can modulate human pDC function and may be applied in disease preven-tion and treatment.

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