The Low-Density Lipoprotein Receptor-Related Protein-1 Is Essential for Dengue Virus Infection.

Dengue virus (DENV) causes the most prevalent and rapidly spreading arboviral disease of humans. It enters human cells by receptor-mediated endocytosis. Numerous cell-surface proteins were proposed as DENV entry factors.

Altered memory CCR6 Th17-polarised T-cell function and biology in people with HIV under successful antiretroviral therapy and HIV elite controllers.

Background: Despite successful antiretroviral therapy (ART), frequencies and immunological functions of memory CCR6 Th17-polarised CD4 T-cells are not fully restored in people with HIV (PWH). Moreover, long-lived Th17 cells contribute to HIV persistence under ART. However, the molecular mechanisms underlying these observations remain understudied.

Dynamics of pulmonary mucosal cytotoxic CD8 T-cells in people living with HIV under suppressive antiretroviral therapy.

Background: Despite the success of antiretroviral therapy (ART), people living with HIV (PLWH) suffer from a high burden of pulmonary diseases, even after accounting for their smoking status. Cytotoxic CD8 T-cells are likely implicated in this phenomenon and may act as a double-edged sword. While being essential in viral infection control, their hyperactivation can also contribute to lung mucosal tissue damage.

Efficient enzyme-free method to assess the development and maturation of the innate and adaptive immune systems in the mouse colon.

Researchers who aim to globally analyze the gastrointestinal immune system via flow cytometry have many protocol options to choose from, with specifics generally tied to gut wall layers of interest. To get a clearer idea of the approach we should use on full-thickness colon samples from mice, we first undertook a systematic comparison of three tissue dissociation techniques: two based on enzymatic cocktails and the other one based on manual crushing. Using flow cytometry panels of general markers of lymphoid and myeloid cells, we found that the presence of cell-surface markers and relative cell population frequencies were more stable with the mechanical method.

Impact of HIV infection on human thymic regulatory T cell differentiation.

Background: The differentiation and function of immunosuppressive regulatory T cells (Tregs) is dictated by the master transcription factor FoxP3. During HIV infection, there is an increase in Treg frequencies in the peripheral blood and lymphoid tissues. This accentuates immune dysfunction and disease progression.

SARS-CoV-2 Vaccine-Induced T-Cell Response after Three Doses in People Living with HIV on Antiretroviral Therapy Compared to Seronegative Controls (CTN 328 COVAXHIV Study).

People living with HIV (PLWH) may be at risk for poor immunogenicity to certain vaccines, including the ability to develop immunological memory. Here, we assessed T-cell immunogenicity following three SARS-CoV-2 vaccine doses in PLWH versus uninfected controls. Blood was collected from 38 PLWH on antiretroviral therapy and 24 age-matched HIV-negative controls, pre-vaccination and after 1st/2nd/3rd dose of SARS-CoV-2 vaccines, without prior SARS-CoV-2 infection.

Immuno-metabolic control of the balance between Th17-polarized and regulatory T-cells during HIV infection.

Th17-polarized CD4 effector T-cells together with their immunosuppressive regulatory T-cell (Treg) counterparts, with transcriptional profiles governed by the lineage transcription factors RORγt/RORC2 and FOXP3, respectively, are important gatekeepers at mucosal interfaces. Alterations in the Th17/Treg ratios, due to the rapid depletion of Th17 cells and increased Treg frequencies, are a hallmark of both HIV and SIV infections and a marker of disease progression. The shift in Th17/Treg balance, in favor of increased Treg frequencies, contributes to gut mucosal permeability, immune dysfunction, and microbial translocation, subsequently leading to chronic immune activation/inflammation and disease progression.

FoxP3 CD8 T-cells in acute HIV infection and following early antiretroviral therapy initiation.

Objectives: Besides CD4 regulatory T-cells (Tregs), immunosuppressor FoxP3 CD8 T-cells are emerging as an important subset of Tregs, which contribute to immune dysfunction and disease progression in HIV infection. However, FoxP3 CD8 T-cell dynamics in acute HIV infection and following early antiretroviral therapy (ART) initiation remain understudied.

Methods: Subsets of FoxP3 CD8 T-cells were characterized both prospectively and cross-sectionally in PBMCs from untreated acute (n=26) and chronic (n=10) HIV-infected individuals, early ART-treated in acute infection (n=10, median of ART initiation: 5.

Impact of Early ARV Initiation on Relative Proportions of Effector and Regulatory CD8 T Cell in Mesenteric Lymph Nodes and Peripheral Blood During Acute SIV Infection of Rhesus Macaques.

CD8 T cells are key players in the clearance of human immunodeficiency virus (HIV)-infected cells, such that CD8 T-cell dysfunction contributes to viral persistence despite antiretroviral (ARV) therapy. Mesenteric lymph nodes (MLNs) are major sites of gut mucosal immunity. While different CD8 T cell subsets such as CD8 alpha-alpha (CD8αα), CD8 alpha-beta (CD8αβ), CD8 regulatory T cells (Treg), and mucosa-associated invariant T cells (MAIT) are present in the gut and exhibit distinct functions, their dynamics remain poorly understood due to the lack of accessibility to these tissues in humans.

Dynamics and epigenetic signature of regulatory T-cells following antiretroviral therapy initiation in acute HIV infection.

Background: HIV infection promotes the expansion of immunosuppressive regulatory T-cells (Tregs), contributing to immune dysfunction, tissue fibrosis and disease progression. Early antiretroviral treatment (ART) upon HIV infection improves CD4 count and decreases immune activation. However, Treg dynamics and their epigenetic regulation following early ART initiation remain understudied.

Antiretroviral therapy-treated HIV-infected adults with coronary artery disease are characterized by a distinctive regulatory T-cell signature.

Background: Despite the success of antiretroviral therapy (ART) to control viral replication, people living with HIV (PWH) have high levels of chronic systemic inflammation and immune dysregulation which drives accelerated co-morbidities including coronary artery disease (CAD). Regulatory T cells (Tregs) and ectonucleotidases CD39/CD73 are known to be athero-protective via their immunosuppressive and anti-inflammatory functions.

Design: We assessed the dynamics of Treg subsets in ART-treated PWH with or without CAD vs.

Impact of extended-release niacin on immune activation in HIV-infected immunological non-responders on effective antiretroviral therapy.

Background: Tryptophan (Trp) catabolism into immunosuppressive kynurenine (Kyn) is involved in immune dysregulation during HIV infection. Niacin (vitamin B3) could control the excess of tryptophan depletion and represents a potential strategy to improve immune functions and CD4 count recovery in immunological non-responder HIV-infected individuals on antiretroviral therapy (ART).

Methods: In the CTN PT006 phase 2 pilot randomized trial, 20 adults on ART with CD4 ≤ 350 cells/µl, despite an undetectable viral load (VL) for at least 3 months, received 2000 mg of extended-release (ER)-niacin orally once daily for 24 weeks.

Differential Dynamics of Regulatory T-Cell and Th17 Cell Balance in Mesenteric Lymph Nodes and Blood following Early Antiretroviral Initiation during Acute Simian Immunodeficiency Virus Infection.

Increased frequencies of immunosuppressive regulatory T cells (Tregs) are associated with gut lymphoid tissue fibrosis and dysfunction which, in turn, contribute to disease progression in chronic simian immunodeficiency virus/human immunodeficiency virus (SIV/HIV) infection. Mesenteric lymph nodes (MLNs), which drain the large and small intestine, are critical sites for the induction and maintenance of gut mucosal immunity. However, the dynamics of Tregs in MLNs are not well understood due to the lack of accessibility to these tissues in HIV-infected individuals.

An "on-matrix" digestion procedure for AP-MS experiments dissects the interplay between complex-conserved and serotype-specific reactivities in Dengue virus-human plasma interactome.

The interactions between the four Dengue virus (DENV) serotypes and plasma proteins are crucial in the initial steps of viral infection to humans. Affinity purification combined with quantitative mass spectrometry analysis, has become one of the most powerful tools for the investigation on novel protein-protein interactions. Using this approach, we report here that a significant number of bait-interacting proteins do not dissociate under standard elution conditions, i.

Dataset on protein composition of a human plasma sub-proteome able to modulate the Dengue 2 virus infection in Huh 7.5 cells.

The four serotypes of dengue virus (DENV1-4) are the causal agents of the emerging disease Dengue Fever and its severe forms. DENV is inoculated into human blood through a mosquito bite. Thus, plasma is an important media for DENV dissemination in infected persons and several important interactions should take place for the virus with human plasma proteins that strongly influence or may determine the course of the infection.

Novel interactions of domain III from the envelope glycoprotein of dengue 2 virus with human plasma proteins.

Unlabelled: Blood cells and plasma are important media for the four serotypes of dengue virus (DENV1-4) spreading into an infected person. Thus, interactions with human plasma proteins are expected to be decisive in the course of the viral infection. Affinity purification followed by MS analysis (AP/MS) was used to isolate and identify plasma-derived proteins capable to interact with a recombinant protein comprising the domain III of the envelope protein of DENV2 (DIIIE2).

Receptor-activated human α2-macroglobulin interacts with the envelope protein of dengue virus and protects virions from temperature-induced inactivation through multivalent binding.

Based on the hypothesis that interactions between virions and serum components may influence the outcome of dengue virus (DENV) infections, we decided to use affinity chromatography with domain III from the envelope (E) protein of DENV2 (DIIIE2) as a ligand to isolate virus-binding proteins from human plasma. This approach yielded serum amyloid P (SAP) and α2-macroglobulin (α2M) as novel viral interactors. After confirming the specific binding of both SAP and α2M to DIIIE2 by ELISA, the latter interaction was examined in greater detail.