DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) is a type II C-type lectin that functions as an adhesion molecule located on dendritic cells (DCs). It enables some of the functions of DCs, including migration, pathogen recognition, internalisation and processing, and their binding to T cells. HIV-1 has been reported to ...

ABSTRACT: BACKGROUND: Repeated exposure to a low dose of a bacterial endotoxin such as lipopolysaccharide (LPS) causes immune cells to become refractory to a subsequent endotoxin challenge, a phenomenon known as endotoxin tolerance (ET). During ET, there is an imbalance in pro- and anti-inflammatory cytokine and chemokine production, leading to ...

The realization of a major role for events that occur during acute viremia that dictate the course of disease both in HIV-1 infected humans and susceptible SIV infected non-human primates has prompted an intense interest in studies of the contribution of innate immune effector mechanisms. It is reasoned that findings ...

The existence of long-lasting cellular reservoirs of HIV-1 is one of the major hurdles in developing effective anti-retroviral therapies. These latently infected cells and tissues efficiently evade immune responses and remain dormant until activated, upon which they can generate a productive HIV-1 infection. This classic scenario of viral latency becomes ...

The lower gastrointestinal tract is a major mucosal site of HIV entry and initial infection. Thus, the induction of strong cellular immune responses at this mucosal site will be an important feature of an effective HIV vaccine. We have used a novel prime-boost vaccination approach to induce immune responses at ...

A case control study was performed to determine the effects of HIV-1-specific cellular immune responses on the odds of acquiring a second HIV-1 infection (superinfection). Changes in the frequency of cytokine-producing or cytolytic CD8+ or CD4+ T cells were not associated with significant alterations in the odds of superinfection, suggesting ...

In macrophages HIV-1 accumulates in intracellular vesicles designated virus containing compartments (VCC). These might play an important role in the constitution of macrophages as viral reservoirs and allow HIV-1 to evade the immune system by sequestration in an internal niche, which is difficult to access from the exterior. However until ...

Chronic immune activation, triggered by plasmacytoid dendritic cell (PDC) interferon (IFN)-alpha production, plays an important role in HIV-1 pathogenesis. As the entry of HIV-1 seems to be important for the activation of PDC, we directly characterized the viral entry into these cells using immuno-electron microscopy, cellular fractionation, confocal imaging, and ...

Following transmission of human immunodeficiency virus (HIV) into a new host, cells of the monocyte/macrophage lineage play a central role in host invasion and viral replication. In particular, macrophages survive infection and support long-standing viral replication, contributing to viral persistence within the host and representing a viral reservoir in vivo. ...

Interferon-stimulated genes fulfill innate antiviral effector functions. Among them, tetherin (THN) blocks the release of many enveloped viruses from infected cells. Vaccinia (VACV) encodes immune modulators interfering with antiviral host responses. Therefore, it was tempting to study a potential VACV-THN interaction. Remarkably, THN expression did not inhibit VACV release and ...

Respiratory syncytial virus (RSV) interaction with epithelial and dendritic cells (DC) is known to require divalent cations suggesting involvement of C-type lectins. RSV infection and maturation of primary human DCs are reduced in a dose-dependent manner by EDTA. Therefore, we asked whether RSV infection involves DC-SIGN (CD209) or its isoform ...

Chemokines are critical components of the immune system that participate in immune homeostasis and alterations in chemokine balance can result in severe inflammatory and autoimmune diseases. The role of chemokines and their receptors in viral infections including HIV-1 was predicted from the early studies of HIV-1 co-receptor CCR5 and its ...

Macrophages are important target cells for HIV-1 infection that play significant roles in the maintenance of viral reservoirs and other aspects of pathogenesis. Understanding the determinants of HIV-1 tropism for macrophages will inform HIV-1 control and eradication strategies. Tropism for macrophages is both qualitative (infection or not) and quantitative (replication ...

Dendritic cells (DCs) initiate immune responses by transporting antigens and migrating to lymphoid tissues to initiate T-cell responses. DCs are located in the mucosal surfaces that are involved in human immunodeficiency virus (HIV) transmission and they are probably among the earliest targets of HIV-1 infection. DCs have an important role ...

Onsets of bacterial infections devastate the compromised immune system in AIDS patients. Damaged gut mucosa permits dissemination of bacterial toxins into deeper layers and hyper-activation of the immune system. We previously reported that the unfractionated supernatants of HIV-resistant CD4(+) T cells impeded the NF-κB/DNA binding in macrophages induced by either ...

LILRs represent a group of immunomodulatory molecules that regulate the functional properties of professional APCs and influence immune activation in a variety of disease contexts. Many members of the LILR family recognize peptide/MHC class I complexes as their physiological ligands, and increasing evidence suggests that such interactions are prominently influenced ...

HIV-associated neurocognitive disorder (HAND) is an increasingly common, progressive disease characterized by neuronal loss and progressively deteriorating CNS function. HIV-1 gene products, particularly gp120 and Tat elicit reactive oxygen species (ROS) that lead to oxidant injury and cause neuron apoptosis. Understanding of, and developing therapies for, HAND requires accessible models ...

Two groups have identified SAMHD1, a protein encoded by an Aicardi-Goutières Syndrome susceptibility gene, as the factor that restricts infection of macrophages and dendritic cells with HIV-1. Here we discuss implications of this discovery for induction of antiviral protective immunity.

Dendritic cells have critical roles for generating and fine-tuning adaptive immune responses and for regulating immune activity through cytokine secretion. In this study, we analyzed functional properties of dendritic cells in primary human immunodeficiency virus type 1 (HIV-1) infection. We found substantial disarray of the functional properties of myeloid and ...

Abstract Adult T-cell leukemia (ATL) is caused by HTLV-I. The viral Tax oncoprotein plays a central role in initiating the process to ATL. However, after infection HTLV-1 enters into latency, during which virus gene expression is very low, so that the level of Tax is likely insufficient for exerting its ...

Bovine herpes virus 1 (BHV-1) infection induces clinical symptoms in the upper respiratory tract, inhibits immune responses, and can result in life-threatening secondary bacterial infections. Following acute infection, BHV-1 establishes latency in sensory neurons within trigeminal ganglia. Periodically, reactivation from latency occurs resulting in virus transmission. The latency-related (LR) RNA ...

Chronic HIV-1 infection is characterized by immune cell dysfunctions driven by chronic immune activation. Plasma HIV-1 viral load (VL) is closely correlated to disease progression and the level of immune activation. However, the mechanism by which the persistent presence of HIV-1 damages immune cells is still not fully understood. To ...

Macrophage colony stimulating factor (M-CSF) is a cytokine that promotes monocyte differentiation and survival. When overexpressed, M-CSF contributes to pathology in a wide variety of diseases, including osteoporosis, obesity, certain human cancers, and in human immunodeficiency virus type 1 (HIV-1) infection, particularly with respect to monocyte/macrophage infection and the development ...

Relatively little is known with regards to the mechanisms of HIV-1 transmission across a mucosal surface and more specifically what effects host factors have on influencing infection and early viral dissemination. The purpose of this review is to summarize which factors of the innate immune response can influence mucosal transmission ...

Acute HIV-1 infection (AHI) is composed of the eclipse phase, during which the transmitted virus struggles to avoid eradication and achieve amplification/spread; the expansion phase when virus disseminates and undergoes exponential replication associated with extensive CD4⁺ T-cell destruction; and the containment phase when set-point levels of viremia and immune activation ...

In this review, we examine how a subset of signal transduction cascades initiated by Mycobacterium tuberculosis (Mtb) infection modulates transcription mediated by the human immunodeficiency virus type 1 long terminal repeat (HIV-1 LTR). We describe two distinct phases of signaling that target transcription factors known to bind the HIV-1 LTR, ...

The activity of raltegravir and 4 other integrase inhibitors (MK-2048, L870,810, IN2, and IN5) was investigated in primary human macrophages, PBMC and C8166-lymphocytic T cells, in order to determine their relative potency and efficacy in different cellular systems of HIV infection. Raltegravir showed better protective efficacy in all cell types; ...

CD4(+) CD25(+) regulatory T cells (Tregs) represent a unique T-cell lineage that is endowed with the ability to actively suppress immune responses in order to inhibit pathogenic damage resulting from over activation of the immune system. In human immunodeficiency virus-1 (HIV-1) infection, suppression of the immune response by Tregs appears ...

Lozach and colleagues show that phleboviruses (bunyaviridae), which comprise important emerging viral pathogens, exploit the C-type lectin DC-SIGN for dendritic cell binding, entry, and infection. The authors elegantly visualize the cellular processes underlying DC-SIGN-dependent viral capture and uptake.

PURPOSE OF REVIEW: This review summarizes recent findings on how HIV-1 infection affects dendritic cells in their ability to elicit innate and adaptive immune responses. RECENT FINDINGS: The phenomenon describing a reduction of dendritic cell numbers in the blood of HIV-1-infected individuals has been expanded on in recent studies demonstrating ...

HIV infection affects the central nervous system resulting in HIV associated neurocognitive disorder (HAND), which is characterized by depression, behavioral and motor dysfunctions. The HIV-1 viral envelope protein gp120 is known to induce the release of neurotoxic factors which lead to apoptotic cell death. Although the exact mechanisms involved in ...

PURPOSE OF REVIEW: Our understanding of the early events in HIV-1 infection continues to grow, along with the heightened recognition of the important contribution that innate immunity plays in response to HIV-1. Here, we review the epidemiological and functional studies of genetic polymorphisms associated with innate immune factors that are ...

PURPOSE OF REVIEW: The early stage of HIV-1 infection is when the virus is most vulnerable, and should therefore offer the best opportunity for therapeutic interventions. This review addresses the recent progress in the understanding of innate immune responses against HIV-1 with focus on the potential targets for prevention of ...

PURPOSE OF REVIEW: Macrophages play an important role in HIV-1 pathogenesis and contribute to the establishment of the viral reservoir responsible for continuous virus production. This review will discuss new insights into HIV-1 infection in macrophages and the effect of infection on immune function and pathology. RECENT FINDINGS: New cellular ...

The RNA interference pathway is a mechanism to regulate gene expression that acts in mammalian antiviral immunity as a complement of interferon- and cytokine-based innate immunity. RNA interference has been proposed as an ancient mechanism against viruses since several components of this system show an effect against viral replication. In ...

As an early response to infection, cells induce a profile of the early inflammatory proteins including antiviral cytokines and chemokines. Two families of transcriptional factors play a major role in the transcriptional activation of the early inflammatory genes: The well-characterized family of NFkB factors and the family of interferon regulatory ...

Trichosanthin (TCS) is a type I ribosome-inactivating protein with wide spectrum of pharmacological activities. It inhibits human immunodeficiency virus type 1 (HIV-1) and Herpes simplex virus type 1 (HSV-1) replication but the mechanism is not clear. From a previous study, TCS was found to be more cytotoxic to HIV-1 infected ...

Macrophages and dendritic cells have key roles in viral infections, providing virus reservoirs that frequently resist antiviral therapies and linking innate virus detection to antiviral adaptive immune responses. Human immunodeficiency virus 1 (HIV-1) fails to transduce dendritic cells and has a reduced ability to transduce macrophages, due to an as ...

Upon activation, CD4(+) T cells release cytokines, chemokines, and other soluble factors that influence the kinetics of HIV-1 replication in macrophages (M). In this article, we show that activation of human primary T cells suppresses the early stages of HIV-1 replication in human primary M by downregulating the main cellular ...

BACKGROUND:: The concept of HIV-1/HSV negative immuno-synergy has recently come to light, which leads us to explore the impact of HIV-1 infection on HSV-specific T cell immunity. METHODS:: A combination of interferon (IFN)-γ-ELISpot and Luminex-based multi-cytokine profiling assays was used to compare, in a cross-sectional study, the HSV-specific CD4 and ...

Abstract HIV infections are mainly acquired by mucosal transmission, through oral, rectal, or genital mucosa. Epithelial cells (EC) are the first cells encountered by HIV during infection through sexual transmission and breastfeeding. EC express several receptors critical for both primary HIV infection and secondary transmission. The regulation of co-receptor expression ...

Subversion or exacerbation of antigen-presenting cells (APC) death modulates host/pathogen equilibrium. We demonstrated during in vitro differentiation of monocyte-derived macrophages and monocyte-derived dendritic cells (DCs) that HIV sensitizes the cells to undergo apoptosis in response to TRAIL and FasL, respectively. In addition, we found that HIV-1 increased the levels of ...

HIV-1 does not significantly activate cellular immunity, which has made it difficult to use attenuated forms of HIV-1 as a vaccine. In contrast, EBV induces robust T cell responses in most infected individuals, perhaps as this virus contains LMP1, a viral mimic of CD40, which is a key activating molecule ...

Apoptosis and autophagy are the two major types of programmed cell death (PCD) in neurons. Homeostatic autophagy often precedes apoptosis, and when apoptosis is blocked, the failure to keep homeostasis will lead to necrosis instead. It has been reported that human immunodeficiency virus (HIV) infected methamphetamine (Meth) abusers represent greater ...

Tissue macrophages are derived exclusively from blood monocytes, which as monocyte-derived macrophages support HIV-1 replication. However, among human tissue macrophages only intestinal macrophages are non-permissive to HIV-1, suggesting that the unique microenvironment in human intestinal mucosa renders lamina propria macrophages non-permissive to HIV-1. We investigated this hypothesis using blood monocytes ...

In order to propagate and persist within the host, HIV-1 subverts a variety of checkpoints of innate and adaptive viral immunosurveillance. Many of these are related to natural killer cells, which bridge innate and adaptive immunity and play a major role in defeating virus infections. HIV-1 affects cytotoxicity of natural ...

Excessive fibroblast expansion and extracellular matrix (ECM) deposition are key events for the development of bowel stenosis in Crohn's disease (CD) patients. Tocotrienols are vitamin E compounds with proven in vitro antifibrogenic effects on rat pancreatic fibroblasts. We aimed at investigating the effects of tocotrienols on human intestinal fibroblast (HIF) ...

During inflammatory bowel disease, TNFα is the major pro-inflammatory cytokine mainly secreted from macrophages and dendritic cells. Here, we have demonstrated that TNFα siRNA/polyethyleneimine loaded into polylactide at an optimal concentration of 20 g/L nanoparticles covered with polyvinyl alcohol are efficiently taken up by inflamed macrophages and inhibit TNFα secretion ...

HIV replication in mononuclear phagocytes is a multi-step process regulated by viral and cellular proteins with the peculiar feature of virion budding and accumulation in intra-cytoplasmic vesicles. Interaction of urokinase-type plasminogen activator (uPA) with its cell surface receptor (uPAR) has been shown to favor virion accumulation in such sub-cellular compartment ...

Chemokines are small chemoattractant cytokines involved in cell trafficking and activation. Despite the general nonspecific nature of chemokine activity in certain instances, specific chemokine expression patterns have been associated with specific disease states. In the field of respiratory viral infection, evidence suggests that response to viral invasion is regulated by ...