The β-adrenergic receptor links sympathetic nerves to T cell exhaustion.

CD8 T cells are essential components of the immune response against viral infections and tumours, and are capable of eliminating infected and cancerous cells. However, when the antigen cannot be cleared, T cells enter a state known as exhaustion. Although it is clear that chronic antigen contributes to CD8 T cell exhaustion, less is known about how stress responses in tissues regulate T cell function.

PD-1CXCR5CD4 peripheral helper T cells promote CXCR3 plasmablasts in human acute viral infection.

T cell-B cell interaction is the key immune response to protect the host from severe viral infection. However, how T cells support B cells to exert protective humoral immunity in humans is not well understood. Here, we use COVID-19 as a model of acute viral infections and analyze CD4 T cell subsets associated with plasmablast expansion and clinical outcome.

Patients with HIV-associated cancers have evidence of increased T cell dysfunction and exhaustion prior to cancer diagnosis.

Background: People living with HIV (PLWH) have increased risk of developing cancers after controlling traditional risk factors and viral suppression. This study explores whether T cells can serve as a marker of risk for cancer among HIV-infected virally suppressed patients.

Methods: A nested case control study design was pursued with 17 cancer cases and 73 controls (PLWH without cancer)ouidentified among the US Military HIV Natural History Study cohort, and were matched for CD4 + count, duration of HIV infection, and viral suppression.

Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8 T cells in tumors.

A common metabolic alteration in the tumor microenvironment (TME) is lipid accumulation, a feature associated with immune dysfunction. Here, we examined how CD8 tumor infiltrating lymphocytes (TILs) respond to lipids within the TME. We found elevated concentrations of several classes of lipids in the TME and accumulation of these in CD8 TILs.

Comparative Evaluation of Prophylactic SIV Vaccination Modalities Administered to the Oral Cavity.

Attempts to develop a protective human immunodeficiency virus (HIV) vaccine have had limited success, especially in terms of inducing protective antibodies capable of neutralizing different viral strains. As HIV transmission occurs mainly via mucosal surfaces, HIV replicates significantly in the gastrointestinal tract, and the oral route of vaccination is a very convenient one to implement worldwide, we explored three SIV vaccine modalities administered orally and composed of simian immunodeficiency virus (SIV) DNA priming with different boosting immunogens, with the goal of evaluating whether they could provide lasting humoral and cellular responses, including at mucosal surfaces that are sites of HIV entry. Twenty-four Cynomolgus macaques (CyM) were primed with replication-incompetent SIV DNA provirus and divided into three groups for the following booster vaccinations, all administered in the oral cavity: Group 1 with recombinant SIV gp140 and heat-labile toxin adjuvant dmLT, Group 2 with recombinant SIV-Oral Poliovirus (SIV-OPV), and Group 3 with recombinant SIV-modified vaccinia ankara (SIV-MVA).

Clinical validation of urine-based Xpert® MTB/RIF assay for the diagnosis of urogenital tuberculosis: A systematic review and meta-analysis.

Objectives: Effective methods for diagnosing urogenital tuberculosis (UGTB) are important for its clinical management. Therefore, we undertook a systematic review to assess the performance of the urine-based Xpert MTB/RIF assay for UGTB.

Methods: PubMed, Embase, Web of Science, the Cochrane library, and Scopus were systematically searched up to July 30, 2019.

Inhibition of p38 MAPK in combination with ART reduces SIV-induced immune activation and provides additional protection from immune system deterioration.

Differences in immune activation were identified as the most significant difference between AIDS-susceptible and resistant species. p38 MAPK, activated in HIV infection, is key to induction of interferon-stimulated genes and cytokine-mediated inflammation and is associated with some of the pathology produced by HIV or SIV infection in AIDS-susceptible primates. As small molecule p38 MAPK inhibitors are being tested in human trials for inflammatory diseases, we evaluated the effects of treating SIV-infected macaques with the p38 MAPK inhibitor PH-797804 in conjunction with ART.

Expression of complement receptor 3 (CR3) and regulatory protein CD46 on dendritic cells of antiretroviral naïve and treated HIV-1 infected individuals: Correlation with immune activation status.

During infection and budding, human immunodeficiency virus-1 (HIV-1) acquires regulators of Complement Activation (RCAs) along with the host cell membrane on the viral envelope. Activation of host complement system results in opsonization of virus by complement fragments, however the virus evades complement mediated lysis (CoML) by virtue of the RCAs on the viral envelope. The RCAs on HIV-1 envelope process complement protein C3 into various fragments that promote viral entry and infection of cells through different complement receptors.

Alterations in B Cell Compartment Correlate with Poor Neutralization Response and Disease Progression in HIV-1 Infected Children.

Several B cell defects are reported in HIV-1 infected individuals including variation in B cell subsets, polyclonal B cell activation and exhaustion, with broadly neutralizing antibodies elicited in less than 10-20% of the infected population. HIV-1 disease progression is faster in children than adults. B Lymphocyte Stimulator (BLyS), expressed on dendritic cells (DCs), is a key regulator of B cell homeostasis.

Association of DC-SIGNR Expression in Peripheral Blood Mononuclear Cells with DC-SIGNR Genotypes in HIV-1 Infection.

Dendritic cell-specific intracellular adhesion molecule 3 grabbing nonintegrin related molecule (DC-SIGNR) is a C-type lectin, calcium-dependent carbohydrate-binding protein, which can act as a cell-adhesion and pathogen recognition receptor. DC-SIGNR is known to be highly expressed on liver sinusoidal cells and in the lymph nodes. However, its expression in peripheral blood mononuclear cells (PBMCs) in HIV-1 infection has not been addressed.

The DC-SIGNR 7/5 genotype is associated with high dendritic cell counts and their subsets in patients infected with HIV-1.

Purpose: The aim of this study was to assess peripheral blood dendritic cell (DC) frequencies and Dendritic Cell-specific intracellular adhesion molecule 3 grabbing non-integrin related (DC-SIGNR) genotyping in healthy individuals, injecting drug users and HIV-1 infected individuals and correlate with different clinical parameters from north India.

Methods: Blood from 30 seronegative healthy individuals, 30 injecting drug users, and 30 patients infected with HIV-1 from North India were collected. Peripheral blood DC frequencies were determined by flow cytometry and repeat region polymorphism in DC-SIGNR was performed by PCR.

Polymorphic variants in DC-SIGN, DC-SIGNR and SDF-1 in high risk seronegative and HIV-1 patients in Northern Asian Indians.

A single nucleotide polymorphism (SNP) in SDF-1, the natural ligand for the HIV-1 coreceptor CXCR4, is implicated to have protective effects against HIV-1 infection. Dendritic cells are the first to encounter HIV-1 at mucosal sites and virus binding occurs via receptors known as DC-SIGN. Variations in the number of repeats in the neck region of DC-SIGN and DC-SIGNR are reported to possibly influence host susceptibility to HIV-1 infection.