Role Of Antigen-presenting Cells Research Articles

Dendritic Cell Epithelial Sodium Channel in Inflammation, Salt-Sensitive Hypertension, and Kidney Damage.

Salt-sensitive hypertension is a major risk factor for cardiovascular morbidity and mortality. The pathophysiologic mechanisms leading to different individual BP responses to changes in dietary salt remain elusive. Research in the last two decades revealed that the immune system plays a critical role in the development of hypertension and related end organ damage. Moreover, sodium accumulates nonosmotically in human tissue, including the skin and muscle, shifting the dogma on body sodium balance and its regulation. Emerging evidence suggests that high concentrations of extracellular sodium can directly trigger an inflammatory response in antigen-presenting cells (APCs), leading to hypertension and vascular and renal injury. Importantly, sodium entry into APCs is mediated by the epithelial sodium channel (ENaC). Although the role of the ENaC in renal regulation of sodium excretion and BP is well established, these new findings imply that the ENaC may also exert BP modulatory effects in extrarenal tissue through an immune-dependent pathway. In this review, we discuss the recent advances in our understanding of the pathophysiology of salt-sensitive hypertension with a particular focus on the roles of APCs and the extrarenal ENaC.

Blockade of interleukin 10 potentiates antitumour immune function in human colorectal cancer liver metastases

ObjectiveProgrammed cell death protein 1 (PD-1) checkpoint inhibition and adoptive cellular therapy have had limited success in patients with microsatellite stable colorectal cancer liver metastases (CRLM). We sought to evaluate...

Aquaporin 4 Is A Mediator Of Essential Dendritic Cell Function

Abstract Aquaporins are transmembrane water channels implicated in a range of physiologic functions. We previously reported that Aquaporin 4 (AQP4) is expressed by T cells and treatment with a small molecule AQP4 inhibitor (AER-270) significantly delays T cell mediated mouse heart allograft rejection. Our findings did not exclude a role for antigen presenting cells (APCs), and the purpose of this study is to investigate the requirement for AQP4 in dendritic cell (DC) functions. Stimulation with AQP4−/− spleen APCs with the addition of antigenic peptide, resulted in reduced frequencies of IFNγ producing MAR T cells compared to WT APCs. We confirmed that splenic DCs express AQP4. Bone marrow derived dendritic cells (BMDCs) from WT and AQP4−/− mice were stimulated with LPS or protein antigen, the absence or inhibition of AQP4 resulted in no defects in up-regulation of maturation markers following stimulation. WT and AQP4−/− BMDCs were pulsed with Lucifer Yellow, FITC-dextran and OVA-AF647 to assess antigen uptake with no observable defect after AQP4 inhibition or in AQP4−/− BMDCs. However, AQP4−/− BMDCs pulsed with OVA protein had reduced expression of SIINFEKL peptide-MHC-I complexes. In contrast, when pulsed with OVA-derived SIINFEKL peptide, AER-270 treated WT BMDCs or AQP4−/− BMDCs showed no change in peptide-MHC complex expression suggesting a role for AQP4 in antigen processing. Consistent with this, the absence or inhibition of AQP4 resulted in decreased DQ-OVA signal, indicating that AQP4 is required for the antigen loading into the lysosome. Our data indicate that AQP4 plays a critical role in the processing of antigens by dendritic cells that impacts their ability to prime T cells, and can be therapeutically targeted in a transplant setting. Supported by grants from NIH (R56AI152368-01)

Apolipoprotein E derived from CD11c+ cells ameliorates atherosclerosis

SummaryAtherosclerosis is studied in models with dysfunctional lipid homeostasis—predominantly the ApoE−/− mouse. The role of antigen-presenting cells (APCs) for lipid homeostasis is not clear. Using a LacZ reporter mouse, we showed that CD11c+ cells were enriched in aortae of ApoE−/− mice. Systemic long-term depletion of CD11c+ cells in ApoE−/− mice resulted in significantly increased plaque formation associated with reduced serum ApoE levels. In CD11ccre+ApoEfl/fl and Albumincre+ApoEfl/fl mice, we could show that ≈70% of ApoE is liver-derived and ≈25% originates from CD11c+ cells associated with significantly increased atherosclerotic plaque burden in both strains. Exposure to acLDL promoted cholesterol efflux from CD11c+ cells and cell-specific deletion of ApoE resulted in increased inflammation reflected by increased IL-1β serum levels. Our results determined for the first time the level of ApoE originating from CD11c+ cells and demonstrated that CD11c+ cells ameliorate atherosclerosis by the secretion of ApoE.

Targeting Antigen-Presenting Cells in Multiple Sclerosis Treatment

Multiple sclerosis (MS) is common neurological disease of the central nervous system (CNS) affecting mostly young adults. Despite decades of studies, its etiology and pathogenesis are not fully unraveled and treatment is still insufficient. The vast majority of studies suggest that the immune system plays a major role in MS development. This is also supported by the effectiveness of currently available MS treatments that target immunocompetent cells. In this review, the role of antigen-presenting cells (APC) in MS development as well as the novel therapeutic options targeting those cells in MS are presented. It is known that in MS, peripheral self-antigen-specific immune cells are activated during antigen presentation process and they enter the CNS through the disrupted blood–brain barrier (BBB). Myelin-reactive CD4+ T-cells can be activated by dendritic cells, infiltrating macrophages, microglia cells, or B-cells, which all express MHC class II molecules. There are also suggestions that brain endothelial cells may act as non-professional APCs and present myelin-specific antigens with MHC class II. Similarly, astrocytes, the major glial cells in the CNS, were shown to act as non-professional APCs presenting myelin antigens to autoreactive T-cells. Several currently available MS drugs such as natalizumab, fingolimod, alemtuzumab, and ocrelizumab may modulate antigen presentation in MS. Another way to use this mechanism in MS treatment may be the usage of specific tolerogenic dendritic cells or the induction of tolerance to myelin antigens by peptide vaccines.

Abstract 119: Donor Macrophages Modulate Cellular Rejection After Heart Transplantation

Heart transplant rejection is common and is associated with significant morbidity and mortality. Current immunosuppressive therapies primarily target recipient T-cells and have a multitude of untoward effects including infections, malignancies, and end-organ damage. Recent studies implicate the roles of antigen presenting cells towards pathogenesis of allograft rejection through recruitment and activation of T-cells. The importance of antigen presenting cell origin, identity, and functional importance remains unknown. Using complimentary imaging and single cell RNA sequencing techniques, we show that donor and recipient monocytes and macrophages co-exist after heart transplantation. These myeloid populations have diverse transcriptional signatures that evolve throughout ongoing rejection. Donor macrophages can be defined ontologically and based on their expression of C-C chemokine receptor 2 (CCR2) and expression of MHC-II. Donor CCR2+ and CCR2- populations can be further defined based on their gene expression profiles, highlighting the marked heterogeneity in the donor macrophage population. Selective depletion of CCR2+ macrophages result in prolonged allograft survival. We use longitudinal single cell RNA sequencing to show that donor CCR2+ and CCR2- macrophages have distinct activation mechanisms such that donor CCR2+ macrophages signal through MyD88/NF-kB. Conditional depletion of MyD88 in donor macrophages recapitulates the donor CCR2+ depletion phenotype. Further interrogation of MyD88 conditionally depleted allografts shows reduced T-cell alloreactivity, holding promise for a potential therapeutic target pathway. Together, we show the molecular identity, diversity, and evolution of donor and recipient monocytes and macrophages as well as the functional relevance and activation pathways of donor macrophages in cardiac allografts.

Antigen-Presenting Cells in the Airways: Moderating Asymptomatic Bacterial Carriage.

Bacterial respiratory tract infections (RTIs) are a major global health burden, and the role of antigen-presenting cells (APCs) in mounting an immune response to contain and clear invading pathogens is well-described. However, most encounters between a host and a bacterial pathogen do not result in symptomatic infection, but in asymptomatic carriage instead. The fact that a pathogen will cause infection in one individual, but not in another does not appear to be directly related to bacterial density, but rather depend on qualitative differences in the host response. Understanding the interactions between respiratory pathogens and airway APCs that result in asymptomatic carriage, will provide better insight into the factors that can skew this interaction towards infection. This review will discuss the currently available knowledge on airway APCs in the context of asymptomatic bacterial carriage along the entire respiratory tract. Furthermore, in order to interpret past and futures studies into this topic, we propose a standardized nomenclature of the different stages of carriage and infection, based on the pathogen’s position with regard to the epithelium and the amount of inflammation present.

Skin antigen-presenting cells and wound healing: New knowledge gained and challenges encountered using mouse depletion models.

The role of antigen-presenting cells in the skin immune system, in particular Langerhans cells and dendritic cells, has not been well defined. We recently published a study in 'Immunology' where we reported that the loss of langerin-positive cells in the skin accelerated wound repair in the Lang-DTR mouse. The study published here by Li, et al. reports delayed wound closure following depletion of CD11c-positive cells in the CD11c-DTR mouse. In this commentary, we attribute the differences between these results to several factors that differ between the studies including the depletion of different cell populations; differences in the age and the sex of mice; differences in antibiotic use between the studies; and differences in the location of the biopsies that were taken. Here, we describe the impact of these differences on wound healing and conclude that further standardization of the wound model, and further characterization of the specific cells that are depleted in these mice, is necessary to better understand how antigen-presenting cells contribute to wound healing.

Cross talk between human regulatory T cells and antigen-presenting cells: Lessons for clinical applications.

Regulatory T cells (Tregs) have a critical role in maintaining self-tolerance and immune homeostasis. There is much interest in using Tregs as a cell therapy to re-establish tolerance in conditions such as inflammatory bowel disease and type 1 diabetes, with many ongoing clinical studies testing the safety and efficacy of this approach. Manufacturing of Tregs for therapy typically involves ex vivo expansion to obtain sufficient cell numbers for infusion and comes with the risk of altering the activity of key biological processes. However, this process also offers an opportunity to tailor Treg function to maximize in vivo activity. In this review, we focus on the roles of antigen-presenting cells (APCs) in the generation and function of Tregs in humans. In addition to stimulating the development of Tregs, APCs activate Tregs and provide signals that induce specialized functional and homing marker expression. Cross talk between Tregs and APCs is a critical, often under-appreciated, aspect of Treg biology, with APCs mediating the key properties of infectious tolerance and bystander suppression. Understanding the biology of human Treg-APC interactions will reveal new ways to optimize Treg-based therapeutic approaches.

Abstract IA19: Myeloid cell control of tumor immunity

Abstract While the success of T-cell checkpoint-targeted immunotherapies is predicated on the induction of an effector T-cell response against tumor antigens by potent antigen-presenting cells (APC), very little is known about the APC composition in human tumors during immunotherapy. APC form a diverse population of dendritic cells (DCs) and macrophages (macs) that share the capacity to capture and present cell-associated antigens to T cells and instruct the repertoire and effector versus regulatory function of T lymphocytes. Despite the key role of APC in tumor immunotherapy, targeting the APC compartment has proved difficult. This is because little is known about the APC molecular changes during tumor response or resistance to immunotherapy. In order to develop ways to modulate tumor APC and promote cancer immunity, we sought to gain a deeper understanding of the molecular and functional diversity of APC in human NSCLC. Using paired mass cytometry analysis of tumor/adjacent tissues, we recently identified major changes in APC and T-cell composition in early non-small lung cancer (NSCLC) lesions (Lavin et al., Cell 2017). More recently, we used cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to further measure APC defects in the tumor lesions. CITE-seq analysis of the tumor lesions revealed profound alterations in tumor APC composition including a reduction of cross-presenting DC at the expense of monocyte-derived cells, which correlated with the presence of dysfunctional T cells compared to the adjacent tissue. Accordingly, we found that DC composition and molecular state controlled CD8+ T-cell accumulation at the tumor site and controlled tumor response to checkpoint blockade in preclinical models. Here, I will discuss the strategies we have developed to enhance DC functionality at the tumor site and the challenges that remain. Citation Format: Miriam Merad. Myeloid cell control of tumor immunity [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr IA19.

Dendritic cells mediate the anti-inflammatory action of omega-3 long-chain polyunsaturated fatty acids in experimental autoimmune uveitis.

We previously showed that dietary omega (ω)–3 long-chain polyunsaturated fatty acids (LCPUFAs) suppress inflammation in mice with experimental autoimmune uveitis (EAU). We have now investigated the role of antigen presenting cells (APCs) in this action of ω-3 LCPUFAs. C57BL/6 mice were fed a diet supplemented with ω-3 or ω-6 LCPUFAs for 2 weeks, after which splenocytes were isolated from the mice and cocultured with CD4+ T cells isolated from mice with EAU induced by injection of a human interphotoreceptor retinoid-binding protein peptide together with complete Freund’s adjuvant. The proliferation of and production of interferon-γ and interleukin-17 by T cells from EAU mice in vitro were attenuated in the presence of splenocytes from ω-3 LCPUFA–fed mice as compared with those from mice fed ω-6 LCPUFAs. Splenocyte fractionation by magnetic-activated cell sorting revealed that, among APCs, dendritic cells (DCs) were the target of ω-3 LCPUFAs. Adoptive transfer of DCs from mice fed ω-3 LCPUFAs attenuated disease progression in EAU mice as well as the production of pro-inflammatory cytokines by T cells isolated from these latter animals. The proliferation of T cells from control Balb/c mice was also attenuated in the presence of DCs from ω-3 LCPUFA–fed mice as compared with those from ω-6 LCPUFA–fed mice. Furthermore, T cell proliferation in such a mixed lymphocyte reaction was inhibited by prior exposure of DCs from mice fed an ω-6 LCPUFA diet to ω-3 LCPUFAs in vitro. Our results thus suggest that DCs mediate the anti-inflammatory action of dietary ω-3 LCPUFAs in EAU.

Exploring the role of antigen presenting cells in male genital tract.

Antigen presenting cells (APCs) are a critical mediator between innate and adaptive immune response. APCs have diverse functions in physiological and pathological conditions, such as maintenance of tissue homoeostasis, prevention of autoimmunity and defence against pathogenic microorganisms and cancer cells. Dendritic cells (DCs) and macrophages (Mϕs) are "professional" APCs that internalise and process allo- and autoantigens; then, resulting peptides are exhibited together with major histocompatibility complex (MHC) molecules expressed at the cell surface. MHC-antigen complexes are presented to "naïve" T cells, thereby stimulating proliferation and differentiation of effector and regulatory T cells. The aim of this review was to summarise current understanding of DCs and Mϕs in testis and epididymis. Male reproductive tract environment is characterised by contradictory needs for tolerance against autoantigenic germ cells that appear after the establishment of central tolerance, and the capacity to mount pro-inflammatory innate immune responses against a wide array of sexually transmitted pathogens. Therefore, exploration of the role of APCs in male reproductive organs is helpful to understand mechanisms of male infertility associated with disruption of the delicate equilibrium between immune privilege and inflammation.

Neuroinflammation: Microglia and T Cells Get Ready to Tango.

In recent years, many paradigms concerning central nervous system (CNS) immunology have been challenged and shifted, including the discovery of CNS-draining lymphatic vessels, the origin and functional diversity of microglia, the impact of T cells on CNS immunological homeostasis and the role of neuroinflammation in neurodegenerative diseases. In parallel, antigen presentation outside the CNS has revealed the vital role of antigen-presenting cells in maintaining tolerance toward self-proteins, thwarting auto-immunity. Here, we review recent findings that unite these shifted paradigms of microglial functioning, antigen presentation, and CNS-directed T cell activation, focusing on common neurodegenerative diseases. It provides an important update on CNS adaptive immunity, novel targets, and a concept of the microglia T-cell equilibrium.

Induction of a Regulatory Phenotype in CD3+ CD4+ HLA-DR+ T Cells after Allogeneic Mixed Lymphocyte Culture; Indications of Both Contact-Dependent and -Independent Activation.

Although the observation of major histocompatibility complex II (MHCII) receptors on T cells is longstanding, the explanation for this occurrence remains enigmatic. Reports of an inducible, endogenous expression exist, as do studies demonstrating a protein acquisition from other cells by mechanisms including vesicle transfer. Irrespective of origin, the presence of the human MHCII isotype, human leukocyte antigen DR (HLA-DR), potentially identifies a regulatory T cell population. Using an allogeneic mixed lymphocyte culture (MLC) to induce an antigen-specific immune response, the role of antigen-presenting cells (APCs) for the presence of HLA-DR on cluster of differentiation 3(CD3)+ CD4+ T cells was evaluated. Moreover, a functional phenotype was established for these T cells. It was demonstrated that APCs were essential for HLA-DR on CD3+ CD4+ T cells. Additionally, a regulatory T cell phenotype was induced in CD3+ CD4+ HLA-DR+ responder T cells with an expression of CD25, CTLA-4, CD62L, PD-1, and TNFRII. This phenotype was induced both with and without physical T cell:APC contact, which could reveal novel indications about its functionality. To further investigate contact-independent communication, a phenotype of the small cell-derived vesicles from the MLCs was determined. Yet heterogeneous, this vesicle phenotype displayed contact-dependent differences, providing clues about their intended function in cellular communication.

Collective Genetic Interaction Effects and the Role of Antigen-Presenting Cells in Autoimmune Diseases.

Autoimmune diseases occur when immune cells fail to develop or lose their tolerance toward self and destroy body’s own tissues. Both insufficient negative selection of self-reactive T cells and impaired development of regulatory T cells preventing effector cell activation are believed to contribute to autoimmunity. Genetic predispositions center around the major histocompatibility complex (MHC) class II loci involved in antigen presentation, the key determinant of CD4+ T cell activation. Recent studies suggested that variants in the MHC region also exhibit significant non-additive interaction effects. However, collective interactions involving large numbers of single nucleotide polymorphisms (SNPs) contributing to such effects are yet to be characterized. In addition, relatively little is known about the cell-type-specificity of such interactions in the context of cellular pathways. Here, we analyzed type 1 diabetes (T1D) and rheumatoid arthritis (RA) genome-wide association data sets via large-scale, high-performance computations and inferred collective interaction effects involving MHC SNPs using the discrete discriminant analysis. Despite considerable differences in the details of SNP interactions in T1D and RA data, the enrichment pattern of interacting pairs in reference epigenomes was remarkably similar: statistically significant interactions were epigenetically active in cell-type combinations connecting B cells to T cells and intestinal epithelial cells, with both helper and regulatory T cells showing strong disease-associated interactions with B cells. Our results provide direct genetic evidence pointing to the important roles B cells play as antigen-presenting cells toward CD4+ T cells in the context of central and peripheral tolerance. In addition, they are consistent with recent experimental studies suggesting that the repertoire of B cell-specific self-antigens in the thymus are critical to the effective control of corresponding autoimmune activation in peripheral tissues.

Development of an Antigen-driven Colitis Model to Study Presentation of Antigens by Antigen Presenting Cells to T Cells.

Inflammatory bowel disease (IBD) is a chronic inflammation which affects the gastrointestinal tract (GIT). One of the best ways to study the immunological mechanisms involved during the disease is the T cell transfer model of colitis. In this model, immunodeficient mice (RAG(-/-) recipients) are reconstituted with naive CD4(+) T cells from healthy wild type hosts. This model allows examination of the earliest immunological events leading to disease and chronic inflammation, when the gut inflammation perpetuates but does not depend on a defined antigen. To study the potential role of antigen presenting cells (APCs) in the disease process, it is helpful to have an antigen-driven disease model, in which a defined commensal-derived antigen leads to colitis. An antigen driven-colitis model has hence been developed. In this model OT-II CD4(+) T cells, that can recognize only specific epitopes in the OVA protein, are transferred into RAG(-/-) hosts challenged with CFP-OVA-expressing E. coli. This model allows the examination of interactions between APCs and T cells in the lamina propria.

Ebola Virus Disease Is Characterized by Poor Activation and Reduced Levels of Circulating CD16+ Monocytes.

A number of previous studies have identified antigen-presenting cells (APCs) as key targets of Ebola virus (EBOV), but the role of APCs in human Ebola virus disease (EVD) is not known. We have evaluated the phenotype and kinetics of monocytes, neutrophils, and dendritic cells (DCs) in peripheral blood of patients for whom EVD was diagnosed by the European Mobile Laboratory in Guinea. Acute EVD was characterized by reduced levels of circulating nonclassical CD16+ monocytes with a poor activation profile. In survivors, CD16+ monocytes were activated during recovery, coincident with viral clearance, suggesting an important role of this cell subset in EVD pathophysiology.

Dendritic cells as therapeutic targets in neuroinflammation.

Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disorder of the central nervous system characterized by infiltration of immune cells and progressive damage to myelin sheaths and neurons. There is still no cure for the disease, but drug regimens can reduce the frequency of relapses and slightly delay progression. Myeloid cells or antigen-presenting cells (APCs) such as dendritic cells (DC), macrophages, and resident microglia, are key players in both mediating immune responses and inducing immune tolerance. Mounting evidence indicates a contribution of these myeloid cells to the pathogenesis of multiple sclerosis and to the effects of treatment, the understanding of which might provide strategies for more potent novel therapeutic interventions. Here, we review recent insights into the role of APCs, with specific focus on DCs in the modulation of neuroinflammation in MS.

The Role of Antigen Presenting Cells in the Pathophysiology of Dry Eye

PurposeDry eye (DE) disease is perpetuated by self‐antigen driven autoimmune‐based inflammation. During the initiation of desiccating stress (DS)‐induced DE acute cytokine production and dendritic cell activation precedes autoreactive CD4 + T cell activation, and CD4 + T cells isolated from these DE mice are sufficient to mediate disease following adoptive transfer to T cell‐deficient nude recipient mice.MethodsFlow cytometry, IHC, ELISA and ocular surface antigen presenting cell (APC)‐depletion were used to phenotype expression and function of dendritic cells and cytokines during DS‐DE (induced in C57BL/6 female mice exposed to sc scopolamine (0.5 mg/0.2 ml) TID, humidity <40%, and sustained airflow).ResultsIn response to DS‐induced DE there is a significant increase (p ≤ 0.05) in the expression of CD11cloPDCA+ plasmacytoid dendritic cells (pDCs) and secretion of type I interferons (IFNa/b) in draining cervical lymph nodes (CLN) and ocular surface tissues compared to naïve controls. The higher frequency of pDCs within the CLN correlated with enhanced IFNa levels in both CLN and ocular surface tears (p ≤ 0.05). Furthermore, CD4 + T cells isolated from APC‐depleted mice exposed to DS are not pathogenic; CD4 + T cell infiltration was markedly (p < 0.05) reduced relative to controls, which was associated with an attenuated proinflammatory cytokine/chemokine response.ConclusionsCollectively, these data further support the concept that DE is a localized self‐antigen‐driven autoimmune disease.

The role of antigen presenting cells in the induction of HIV-1 latency in resting CD4(+) T-cells.

BackgroundCombination antiretroviral therapy (cART) is able to control HIV-1 viral replication, however long-lived latent infection in resting memory CD4+ T-cells persist. The mechanisms for establishment and maintenance of latent infection in resting memory CD4+ T-cells remain unclear. Previously we have shown that HIV-1 infection of resting CD4+ T-cells co-cultured with CD11c+ myeloid dendritic cells (mDC) produced a population of non-proliferating T-cells with latent infection. Here we asked whether different antigen presenting cells (APC), including subpopulations of DC and monocytes, were able to induce post-integration latent infection in resting CD4+ T-cells, and examined potential cell interactions that may be involved using RNA-seq.ResultsmDC (CD1c+), SLAN+ DC and CD14+ monocytes were most efficient in stimulating proliferation of CD4+ T-cells during syngeneic culture and in generating post-integration latent infection in non-proliferating CD4+ T-cells following HIV-1 infection of APC-T cell co-cultures. In comparison, plasmacytoid DC (pDC) and B-cells did not induce latent infection in APC-T-cell co-cultures. We compared the RNA expression profiles of APC subpopulations that could and could not induce latency in non-proliferating CD4+ T-cells. Gene expression analysis, comparing the CD1c+ mDC, SLAN+ DC and CD14+ monocyte subpopulations to pDC identified 53 upregulated genes that encode proteins expressed on the plasma membrane that could signal to CD4+ T-cells via cell–cell interactions (32 genes), immune checkpoints (IC) (5 genes), T-cell activation (9 genes), regulation of apoptosis (5 genes), antigen presentation (1 gene) and through unknown ligands (1 gene).ConclusionsAPC subpopulations from the myeloid lineage, specifically mDC subpopulations and CD14+ monocytes, were able to efficiently induce post-integration HIV-1 latency in non-proliferating CD4+ T-cells in vitro. Inhibition of key pathways involved in mDC-T-cell interactions and HIV-1 latency may provide novel targets to eliminate HIV-1 latency.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-015-0204-2) contains supplementary material, which is available to authorized users.