Infection of Specific Dendritic Cells by CCR5-Tropic Human Immunodeficiency Virus Type 1 Promotes Cell-Mediated Transmission of Virus Resistant to Broadly Neutralizing Antibodies

Lakshmanan, Ganesh; Leung, Kwanyee; Loré, Karin; Levin, Reuven; Panet, Amos; Schwartz, Owen; Koup, Richard A.; Nabel, Gary J.

doi:10.1128/jvi.78.21.11980-11987.2004

Cited by 122 publications

(138 citation statements)

References 52 publications

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“…3 B and C) suggests that viral transfer in these secluded regions will be an important factor. A possible consequence of the wrapping of the T cell by the sheet-like envelopes is a reduction in the effective concentration of exogenously added reagents at the site of virus transfer, offering an explanation for the relative inability of neutralizing antibodies to block viral infection at dendritic cell-T-cell synapses in some instances (38). Inhibition of viral entry into CD4 + T cells by therapeutical intervention may thus require higher drug concentrations and local targeting, emphasizing the importance of pursuing complementary strategies aimed at neutralizing viruses at earlier stages in the process of infection such as virus uptake and delivery to T cells.…”

Section: Discussionmentioning

confidence: 99%

3D visualization of HIV transfer at the virological synapse between dendritic cells and T cells

Felts

Narayan

Estes

et al. 2010

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

172

176

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The efficiency of HIV infection is greatly enhanced when the virus is delivered at conjugates between CD4 + T cells and virus-bearing antigen-presenting cells such as macrophages or dendritic cells via specialized structures known as virological synapses. Using ion abrasion SEM, electron tomography, and superresolution light microscopy, we have analyzed the spatial architecture of cell-cell contacts and distribution of HIV virions at virological synapses formed between mature dendritic cells and T cells. We demonstrate the striking envelopment of T cells by sheet-like membrane extensions derived from mature dendritic cells, resulting in a shielded region for formation of virological synapses. Within the synapse, filopodial extensions emanating from CD4 + T cells make contact with HIV virions sequestered deep within a 3D network of surface-accessible compartments in the dendritic cell. Viruses are detected at the membrane surfaces of both dendritic cells and T cells, but virions are not released passively at the synapse; instead, virus transfer requires the engagement of T-cell CD4 receptors. The relative seclusion of T cells from the extracellular milieu, the burial of the site of HIV transfer, and the receptor-dependent initiation of virion transfer by T cells highlight unique aspects of cell-cell HIV transmission.

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Section: Discussionmentioning

confidence: 99%

3D visualization of HIV transfer at the virological synapse between dendritic cells and T cells

Felts

Narayan

Estes

et al. 2010

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

172

176

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“…Contact between DC that have captured HIV with activate or non-activated CD4 lymphocytes leads to efficient transfer of virus to lymphocytes in two distinct phases. The DC and CD4 lymphocyte form a 'infectious synapse' at the contact region [29,30], which is sealed and protected from antibody entry by interaction of the adhesion molecules LFA-1 and ICAM-1 (CD54) [31,32]. CD4 and CCR5 are concentrated at the enclosed lymphocyte membrane.…”

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confidence: 99%

Langerhans cells and viral immunity

2008

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Langerhans cells (LC) are a unique dendritic cell subset that are located in mucosal stratified squamous epithelium and skin epidermis. Their location is ideally suited for their function as antigen presenting cells that capture invading viruses and induce anti-viral immunity. However, it is becoming evident that the interaction between LC and viruses can result in different responses, depending on the virus and the receptors involved. Here we will discuss the recent data on the similarities and differences in roles of LC in viral immunity to and infection with HIV, herpes simplex and varicella-zoster virus. Although all three viruses interact with LC during initial infection, the effects can be quite different, reflecting differences in biology and pathogenesis. Key words: Dendritic cells Á Langerhans cells Á Infectious diseases Á HIV Á HerpesvirusesSee accompanying mini-review by Kaplan et al. Biology of LC and interactions with virusesThe resident epidermal dendritic cells (DC), Langerhans cells (LC), form a tight network with each other and with the surrounding keratinocytes via E-cadherin in the skin or mucosal stratified squamous epithelium. In the anogenital region they are distributed throughout the anogenital skin and mucosa including vagina, ectocervix as well as male foreskin. In stratified squamous epithelium, LC overlie interstitial or dermal DC [1]. LC can repopulate from local and blood-borne precursors (reviewed by Kaplan et al. in this issue [2]). Similar to other myeloid DC, LC are able to bridge innate and adaptive immunity. They are able to interact directly with microorganisms at the periphery to produce effector cytokines and initiate or restimulate activation of T and B lymphocytes through antigen presentation. LC express different pattern recognition receptors such as C-type lectin receptors (CLR) and Toll-like receptors (TLR), to bind and capture pathogens. These interactions result in activation of intracellular signalling pathways leading to LC activation and cytokine induction. The CLR expressed by skin DC differ by site: Langerin by epidermal LC and DC-SIGN and mannose receptor by dermal DC. LC like other migratory DC are in an immature, highly endocytic state while sessile in the skin/mucosa. However after pathogen binding to TLR and uptake, LC become mature and migratory, downregulating their endocytic and antigen processing capacity. Mature LC migrate to the lymph nodes where they are directly or indirectly involved in presentation of pathogenderived antigens on MHC Class I and II to T cells, resulting in activation of antigen-specific T cells [2][3][4]. Recent studies have raised the possibility that LC may have an immunosuppressive role [5][6][7]. Kaplan et al. [2] showed that contact hypersensitivity was amplified on LC ablation, while Cumberbatch et al.[5] found defective LC mobilisation in patients with psoriasis. Immunosuppression rather than stimulation could be explained, in part, by the maturational process associated with LC migration during steady-state conditions. Jian...

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“…The cells were matured in 5 μg/ml of ODN CpG (1829) for 24-48 h. Cells were pretreated with 10 μg/ml bafi lomycin, 5 μg/ml MG132, 100 μM chloroquine, or alone in RPMI for 1 h. Media were then removed, and DCs were pulsed with HIV-1-GFP for 2 h. Cells were washed once with PBS and lysed in 1X p24 cell lysis buff er at time points 0 h, 1 h, and 3 h and stored at −30°C. Lysates were assayed for p24 activity by ELISA (Beckman Coulter HIV-1 p24 Antigen EIA) and read at 450/570 nm dual wavelength on a SPECTRAmax Plus 384 (16)(17)(18)(19)(20)(21)(22).…”

Section: ′ Primer: G G G a G G C T C C A A G A C C T C A T A A T C Tmentioning

confidence: 99%

“…Supernatants were harvested 48 and 72 h after transfection, fi ltered, and stored at −80°C. Virus concentration was determined by an ELISA assay for the p24 antigen (Beckman Coulter) (16)(17)(18)(19)(20)(21)(22).…”

Section: ′ Primer: G G G a G G C T C C A A G A C C T C A T A A T C Tmentioning

confidence: 99%

See 1 more Smart Citation

Leukocyte-specific protein 1 interacts with DC-SIGN and mediates transport of HIV to the proteasome in dendritic cells

Smith¹,

Lakshmanan²,

Leung³

et al. 2007

J Cell Biol

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Infection of Specific Dendritic Cells by CCR5-Tropic Human Immunodeficiency Virus Type 1 Promotes Cell-Mediated Transmission of Virus Resistant to Broadly Neutralizing Antibodies

Cited by 122 publications

References 52 publications

3D visualization of HIV transfer at the virological synapse between dendritic cells and T cells

3D visualization of HIV transfer at the virological synapse between dendritic cells and T cells

Langerhans cells and viral immunity

Leukocyte-specific protein 1 interacts with DC-SIGN and mediates transport of HIV to the proteasome in dendritic cells

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