Clusterin protects mature dendritic cells from reactive oxygen species mediated cell death.

Dendritic cells (DCs) play a key role in the induction of the adaptive immune response. They capture antigens in peripheral tissues and prime naïve T lymphocytes, triggering the adaptive immune response. In the course of inflammatory processes DCs face stressful conditions including hypoxia, low pH and high concentrations of reactive oxygen species (ROS), among others.

Platelets modulate CD4 T-cell function in COVID-19 through a PD-L1 dependent mechanism.

Severe COVID-19 is associated with a systemic inflammatory response and progressive CD4 T-cell lymphopenia and dysfunction. We evaluated whether platelets might contribute to CD4 T-cell dysfunction in COVID-19. We observed a high frequency of CD4 T cell-platelet aggregates in COVID-19 inpatients that inversely correlated with lymphocyte counts.

Extracellular Acidosis and mTOR Inhibition Drive the Differentiation of Human Monocyte-Derived Dendritic Cells.

During inflammation, recruited monocytes can differentiate either into macrophages or dendritic cells (DCs); however, little is known about the environmental factors that determine this cell fate decision. Low extracellular pH is a hallmark of a variety of inflammatory processes and solid tumors. Here, we report that low pH dramatically promotes the differentiation of monocytes into DCs (monocyte-derived DCs [mo-DCs]).

Aberrant fucosylation enables breast cancer clusterin to interact with dendritic cell-specific ICAM-grabbing non-integrin (DC-SIGN).

Clusterin is a glycoprotein able to mediate different physiological functions such as control of complement activation, promotion of unfolded protein clearance and modulation of cell survival. Clusterin is overexpressed in many types of cancers and a large body of evidence suggests that it promotes carcinogenesis and tumor progression. We have previously described a novel clusterin glycoform present in human semen, but not in serum, highly enriched in terminal fucose motifs.

Histidine-Rich Glycoprotein Inhibits HIV-1 Infection in a pH-Dependent Manner.

Histidine-rich glycoprotein (HRG) is an abundant plasma protein with a multidomain structure, allowing its interaction with many ligands, including phospholipids, plasminogen, fibrinogen, IgG antibodies, and heparan sulfate. HRG has been shown to regulate different biological responses, such as angiogenesis, coagulation, and fibrinolysis. Here, we found that HRG almost completely abrogated the infection of Ghost cells, Jurkat cells, CD4 T cells, and macrophages by HIV-1 at a low pH (range, 6.

Prostaglandin E2 Antagonizes TGF-β Actions During the Differentiation of Monocytes Into Dendritic Cells.

Inflammatory dendritic cells (DCs) are a distinct subset of DCs that derive from circulating monocytes infiltrating injured tissues. Monocytes can differentiate into DCs with different functional signatures, depending on the presence of environment stimuli. Among these stimuli, transforming growth factor-beta (TGF-β) and prostaglandin E2 (PGE2) have been shown to modulate the differentiation of monocytes into DCs with different phenotypes and functional profiles.

Low pH impairs complement-dependent cytotoxicity against IgG-coated target cells.

Local acidosis is a common feature of allergic, vascular, autoimmune, and cancer diseases. However, few studies have addressed the effect of extracellular pH on the immune response. Here, we analyzed whether low pH could modulate complement-dependent cytotoxicity (CDC) against IgG-coated cells.

Candida albicans delays HIV-1 replication in macrophages.

Macrophages are one of the most important HIV-1 target cells. Unlike CD4(+) T cells, macrophages are resistant to the cytophatic effect of HIV-1. They are able to produce and harbor the virus for long periods acting as a viral reservoir.

Mechanisms regulating neutrophil survival and cell death.

Neutrophils not only play a critical role as a first line of defense against bacteria and fungi infections but also contribute to tissue injury associated with autoimmune and inflammatory diseases. Neutrophils are rapidly and massively recruited from the circulation into injured tissues displaying an impressive arsenal of toxic weapons. Although effective in their ability to kill pathogens, these weapons were equally effective to induce tissue damage.

Analysis of suppressor and non-suppressor FOXP3+ T cells in HIV-1-infected patients.

Recently, it was shown that peripheral blood FOXP3+CD4+ T cells are composed of three phenotypic and functionally distinct subpopulations. Two of them having in vitro suppressive effects were characterized as resting Treg cells (rTregs) and activated Treg cells (aTregs). A third subset, identified as FOXP3+ non-Tregs, does not display any suppressor activity and produce high levels of Th1 and Th17 cytokines upon stimulation.

Semen promotes the differentiation of tolerogenic dendritic cells.

Seminal plasma is not just a carrier for spermatozoa. It contains high concentrations of cytokines, chemokines, and other biological compounds that are able to exert potent effects on the immune system of the receptive partner. Previous studies have shown that semen induces an acute inflammatory response at the female genital mucosa after coitus.

Epithelial cells activate plasmacytoid dendritic cells improving their anti-HIV activity.

Plasmacytoid dendritic cells (pDCs) play a major role in anti-viral immunity by virtue of their ability to produce high amounts of type I interferons (IFNs) and a variety of inflammatory cytokines and chemokines in response to viral infections. Since recent studies have established that pDCs accumulate at the site of virus entry in the mucosa, here we analyzed whether epithelial cells were able to modulate the function of pDCs. We found that the epithelial cell lines HT-29 and Caco-2, as well as a primary culture of human renal tubular epithelial cells (HRTEC), induced the phenotypic maturation of pDCs stimulating the production of inflammatory cytokines.

Semen clusterin is a novel DC-SIGN ligand.

The C-type lectin receptor dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) is an important player in the recognition of pathogens by dendritic cells. A plethora of pathogens including viruses, bacteria, parasites, and fungi are recognized by DC-SIGN through both mannose and fucose-containing glycans expressed on the pathogen surface. In this study, we identified semen clusterin as a novel DC-SIGN ligand.

The role of semen in sexual transmission of HIV: beyond a carrier for virus particles.

Unprotected sexual intercourse between discordant couples is by far the most frequent mode of HIV-1 (human immunodeficiency virus type 1) transmission being semen the main vector for HIV-1 dissemination worldwide. Semen is usually considered merely as a vehicle for HIV-1 transmission. In this review we discuss recent observations suggesting that beyond being a carrier for virus particles semen markedly influences the early events involved in sexual transmission of HIV through the mucosal barriers.

Spermatozoa capture HIV-1 through heparan sulfate and efficiently transmit the virus to dendritic cells.

Semen is the main vector for HIV-1 dissemination worldwide. It contains three major sources of infectious virus: free virions, infected leukocytes, and spermatozoa-associated virions. We focused on the interaction of HIV-1 with human spermatozoa and dendritic cells (DCs).

Human seminal plasma abrogates the capture and transmission of human immunodeficiency virus type 1 to CD4+ T cells mediated by DC-SIGN.

Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) is expressed by dendritic cells (DCs) at mucosal surfaces and appears to play an important role in the dissemination of human immunodeficiency virus type 1 (HIV-1) infection. DC-SIGN binds HIV-1 gp120 and efficiently transmits the virus to T CD4(+) cells, which become the center of viral replication. Semen represents the main vector for HIV-1 dissemination worldwide.

Extracellular acidosis triggers the maturation of human dendritic cells and the production of IL-12.

Although the development of an acidic tissue environment or acidosis is a hallmark of inflammatory processes, few studies analyze the effect of extracellular pH on immune cells. We have previously shown that exposure of murine dendritic cells (DCs) to pH 6.5 stimulates macropinocytosis and cross-presentation of extracellular Ags by MHC class I molecules.

Sphingosylphosphorylcholine activates dendritic cells, stimulating the production of interleukin-12.

Compared with other lysophospholipid mediators such as sphingosine-1-phosphate and lysophosphatidic acid, little is known about the physiological significance of the related bioactive lysosphingolipid sphingosylphosphorylcholine (SPC), which is present in high-density lipoprotein particles. The present study was undertaken to evaluate the effect of SPC on human immature dendritic cells (DCs). Reverse transcription-polymerase chain reaction and flow cytometry assays revealed that DCs express two putative receptors for SPC, ovarian cancer G-protein-coupled receptor 1 and G-protein-coupled receptor 4.

Interplay of pathogens, cytokines and other stress signals in the regulation of dendritic cell function.

Dendritic cells (DCs) are the only antigen-presenting cell capable of activating naïve T lymphocytes, and hence they play a crucial role in the induction of adaptive immunity. Immature DCs sample and process antigens, and efficiently sense a large variety of signals from the surrounding environment. Upon activation, they become capable to activate naïve T cells and to direct the differentiation and polarization of effector T lymphocytes.

Extracellular acidosis induces neutrophil activation by a mechanism dependent on activation of phosphatidylinositol 3-kinase/Akt and ERK pathways.

Inflammation in peripheral tissues is usually associated with the development of local acidosis; however, there are few studies aimed at analyzing the influence of acidosis on immune cells. We have shown previously that extracellular acidosis triggers human neutrophil activation, inducing a transient increase in intracellular Ca2+ concentration, a shape change response, the up-regulation of CD18 expression, and a delay of apoptosis. In this study, we analyzed the signaling pathways responsible for neutrophil activation.

The impact of extracellular acidosis on dendritic cell function.

Dendritic cells (DCs) are the most efficient antigen-presenting cells. They are activated in the periphery by conserved pathogen molecules and by inflammatory mediators produced by a variety of cell types in response to danger signals. It is widely appreciated that inflammatory responses in peripheral tissues are usually associated with the development of acidic microenvironments.