The C-type lectin surface receptor DCIR acts as a new attachment factor for HIV-1 in dendritic cells and contributes to trans- and cis-infection pathways

Lambert, Alexandra A.; Gilbert, Caroline; Richard, Manon; Beaulieu, André; Tremblay, Michel J.

doi:10.1182/blood-2008-01-136473

Cited by 166 publications

(168 citation statements)

References 49 publications

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“…Cell-surface expression of DCIR was monitored by flow cytometry (Epics ELITE ESP, Coulter Electronics) as described previously. 10 …”

Section: Cells and Flow Cytometric Analysismentioning

confidence: 99%

“…Primary human DCs were generated from purified human monocytes (ie, CD14 ϩ cells) using a previously described procedure. 10 Briefly, CD14 ϩ cells were cultured in 6-well plates at a density of 10 6 cells/mL in 3 mL of RPMI-1640 medium supplemented with 10% FBS. To generate immature monocyte-derived dendritic cells (IM-MDDCs), purified monocytes were cultured in complete culture medium that was supplemented every other day with GM-CSF (1000 U/ mL) and IL-4 (200 U/mL) for 7 days.…”

Section: Cells and Flow Cytometric Analysismentioning

confidence: 99%

“…Although a previous work demonstrated that DCIR is involved in the interaction between HIV-1 and DCs, 10 nothing is known on the precise contribution of DCIR-mediated intracellular signal transducers in virus capture, infection, and eventual transfer. The possible interaction between its ITIM with non-receptor TKs (NRTKs) and protein tyrosine phosphatases (PTPs) in this process also deserves some attention.…”

Section: Introductionmentioning

confidence: 99%

“…Another lectin receptor, that is, the dendritic cell immunoreceptor (DCIR), can behave as an HIV-1 attachment factor for HIV-1 to participate actively in trans infection of CD4 ϩ T cells. 10 DCIR also contributes to cis-infection events, that is, infection of surrounding CD4 ϩ T cells by virions produced by DCs productively infected with HIV-1. 10 DCIR is a member of a recently described family of C-type lectin receptors (CLRs), which includes DCAR, dectin-2, BDCA-2, MCL, and MINCLE.…”

Section: Introductionmentioning

confidence: 99%

“…10 DCIR also contributes to cis-infection events, that is, infection of surrounding CD4 ϩ T cells by virions produced by DCs productively infected with HIV-1. 10 DCIR is a member of a recently described family of C-type lectin receptors (CLRs), which includes DCAR, dectin-2, BDCA-2, MCL, and MINCLE. These receptors carry a single carbohydrate recognition domain (CRD) at the COOH terminal and generally lack consensus signaling motifs in their cytoplasmic region.…”

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confidence: 99%

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DCIR-mediated enhancement of HIV-1 infection requires the ITIM-associated signal transduction pathway

Lambert

Barabé

Gilbert

et al. 2011

Blood

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Dendritic cell immunoreceptor (DCIR) is IntroductionIt is known that cell-free virions do not efficiently cross genital epithelial cells. Instead HIV-1 uses primarily dendritic cells (DCs) to penetrate the mucosal epithelium. 1,2 The virus is then transferred and disseminated from this entry site to T-cell zones in secondary lymphoid organs, where it can productively infect residing CD4 ϩ T cells. The infection process causes a marked depletion of CD4 ϩ T cells, 3 progressive impairment of the immune system, as well as chronic hyperactivation of both CD4 ϩ and CD8 ϩ T cells. 4 The initial attachment step of HIV-1 to DCs may occur through several complex interactions between the virus and the target cell surface (reviewed in Clapham and McKnight 5 and in Ugolini et al 6 ) such as the association between the oligosaccharides found on the external envelope glycoprotein gp120 and the mannose receptor (CD206), langerin (CD207), or 8 This will result in virus capture and transmission to CD4 ϩ T cells in an effective trans mode 9 (ie, transfer of virions bound onto DCs and/or localized in endosomes). Another lectin receptor, that is, the dendritic cell immunoreceptor (DCIR), can behave as an HIV-1 attachment factor for HIV-1 to participate actively in trans infection of CD4 ϩ T cells. 10 DCIR also contributes to cis-infection events, that is, infection of surrounding CD4 ϩ T cells by virions produced by DCs productively infected with HIV-1. 10 DCIR is a member of a recently described family of C-type lectin receptors (CLRs), which includes DCAR, dectin-2, BDCA-2, MCL, and MINCLE. These receptors carry a single carbohydrate recognition domain (CRD) at the COOH terminal and generally lack consensus signaling motifs in their cytoplasmic region. 11 Several members of the family, however, possess a positively charged residue in their transmembrane region, via which they associate with immunoreceptor tyrosine-based activation motif (ITAM)-containing adaptor molecules, such as the Fc receptor ␥ chains. Importantly, DCIR is the only family member harboring an immunoreceptor tyrosine-based inhibitory motif (ITIM), which is involved in modulation of cellular responses. 12 DCIR is expressed on the surface of most antigen-presenting cells (ie DCs, monocytes, macrophages, and B cells), as well as on granulocytes, and it is differentially expressed depending on the DC maturation status. 13 Lipopolysaccharide, IL-4, and TNF-␣ down-regulate DCIR expression on neutrophils. 14 The ITIM domain of DCIR contains the consensus sequence S/I/V/LxYxxI/V/L, including a tyrosine residue at position 7 (ie, ITYAEV). 13 Generally, when ITIM-containing receptors are engaged, they become tyrosine-phosphorylated and then transmit signals by binding and activating Src homology-2 domain (SH2)-containing tyrosine phosphatases (eg, SHP-1 and SHP-2) and/or the SH2-containing tyrosine inositol phosphate (SHIP). 15 In the case of DCIR, one study has demonstrated that, when phosphorylated, it recruits both SHP-1 and SHP-2. 16 Nevertheless, there is still no e...

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“…Cell-surface expression of DCIR was monitored by flow cytometry (Epics ELITE ESP, Coulter Electronics) as described previously. 10 …”

Section: Cells and Flow Cytometric Analysismentioning

confidence: 99%

Section: Cells and Flow Cytometric Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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DCIR-mediated enhancement of HIV-1 infection requires the ITIM-associated signal transduction pathway

Lambert

Barabé

Gilbert

et al. 2011

Blood

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Crystal structure of human dendritic cell inhibitory receptor C‐type lectin domain reveals the binding mode with N‐glycan

et al. 2016

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Human dendritic cell inhibitory receptor (DCIR) is a C-type lectin receptor expressed in classical dendritic cells and accepts several oligosaccharide ligands including N-glycans. Here, we report the crystal structures of human DCIR C-type lectin domains in the absence and presence of a branched N-glycan unit. The domain has a typical C-type lectin fold and two bound calcium ions. In the ligand-bound form, the disaccharide unit (GlcNAcb1-2Man) acceptably fits the electron density map, indicating that it forms the main epitope. The recognition of the nonterminal N-glycan unit explains the relatively broad specificity of this lectin.

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Carbohydrate Binding Agents: Potential Therapeutics with Multiple Inhibitory Actions against Enveloped Viruses

François

Balzarini

2011

Carbohydrate Recognition

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The C-type lectin surface receptor DCIR acts as a new attachment factor for HIV-1 in dendritic cells and contributes to trans- and cis-infection pathways

Cited by 166 publications

References 49 publications

DCIR-mediated enhancement of HIV-1 infection requires the ITIM-associated signal transduction pathway

DCIR-mediated enhancement of HIV-1 infection requires the ITIM-associated signal transduction pathway

Crystal structure of human dendritic cell inhibitory receptor C‐type lectin domain reveals the binding mode with N‐glycan

Carbohydrate Binding Agents: Potential Therapeutics with Multiple Inhibitory Actions against Enveloped Viruses

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