Two-Pore Channels Control Ebola Virus Host Cell Entry and Are Drug Targets for Disease Treatment Researchers found that Ebola virus entry into host cells requires the endosomal calcium channels called two-pore channels (TPCs). Tetrandrine, the most potent small molecule they tested, inhibited infection of human macrophages, the primary target of Ebola virus in vivo, and also showed therapeutic efficacy in mice. [Science] Abstract | Press Release A Bacterial Cyclic Dinucleotide Activates the Cytosolic Surveillance Pathway and Mediates Innate Resistance to Tuberculosis Investigators found that a di-adenylate cyclase 4-overexpressing Mycobacterium tuberculosis strain that secretes excess cyclic-di-adenosine monophosphate activated the interferon regulatory factor pathway with enhanced levels of IFN-β, elicited increased macrophage autophagy, and exhibited substantial virulence attenuation in mice. [Nat Med] Abstract | Press Release Human Monocytes Undergo Functional Re-Programming during Sepsis Mediated by Hypoxia-Inducible Factor-1α Investigators performed a transcriptomic, functional, and mechanistic analysis of blood monocytes from patients during sepsis and after recovery. Their results revealed the functional plasticity of monocytes during human sepsis, wherein they transited from a pro-inflammatory to an immunosuppressive phenotype, while enhancing protective functions like phagocytosis, anti-microbial activity, and tissue remodeling. [Immunity] Abstract | Graphical Abstract Cutaneous Na+ Storage Strengthens the Antimicrobial Barrier Function of the Skin and Boosts Macrophage-Driven Host Defense Scientists used the protozoan parasite Leishmania major as a model of skin-prone macrophage infection to test the hypothesis that skin-Na+ storage facilitates antimicrobial host defense. Activation of macrophages in the presence of high NaCl concentrations modified epigenetic markers and enhanced p38 mitogen-activated protein kinase-dependent nuclear factor of activated T cells 5 activation. [Cell Metab] Full Article | Graphical Abstract | Press Release ​IL-10 Inhibits ​Neuraminidase-Activated TGF-β and Facilitates Th1 Phenotype during Early Phase of Infection In an antigen-specific mouse experimental system, influenza ​hemagglutinin-specific ​CD4+ T cells responded to infection with the induction of ​T-bet, and produced both ​IFN-γ and ​IL-10. In the early phase of infection, an abundance of viral ​neuraminidase caused TGF-β activation of ​hemagglutinin-specific ​CD4+ T cells. [Nat Commun] Abstract Generation of Cellular Immune Memory and B-Cell Immunity Is Impaired by Natural Killer Cells Investigators showed that mouse natural killer cells inhibit generation of long-lived virus-specific memory T- and B cells as well as virus-specific antibody production after acute infection. [Nat Commun] Abstract Viral Entry Route Determines How Human Plasmacytoid Dendritic Cells Produce Type I Interferons Scientists showed that replication of the yellow fever live vaccine YF-17D in human plasmacytoid dendritic cells (pDCs) and pDC-like cell lines stimulated type I interferon production through RIG-I (retinoic acid-inducible gene I), a member of the RIG-I-like receptor family of cytosolic pattern recognition receptors. [Sci Signal] Abstract HIV An Evolutionary Role for HIV Latency in Enhancing Viral Transmission Mathematical modeling indicates that HIV’s Tat positive-feedback circuitry enables this persistence and strongly controls latency. To overcome the inherent crosstalk between viral circuitry and cellular activation and to directly test this hypothesis, investigators synthetically decoupled viral dependence on cellular environment from viral transcription. [Cell] Abstract | Graphical Abstract | Press Release Large Number of Rebounding/Founder HIV Variants Emerge from Multifocal Infection in Lymphatic Tissues after Treatment Interruption Scientists examined lymph node and gut-associated lymphoid tissue (LT) biopsies from fully suppressed subjects, interrupted therapy, monitored plasma viral load (pVL), and repeated biopsies on 12 individuals as soon as pVL became detectable. Isolated HIV RNA-positive cells were detected by in situ hybridization in LTs obtained before interruption in several patients. [Proc Natl Acad Sci USA] Abstract | Full Article Early Antiretroviral Therapy with Raltegravir Generates Sustained Reductions in HIV Reservoirs but Not Lower T-Cell Activation Levels Investigators conducted an open-label, nonrandomized study, monitoring for three years: plasma viral load, T-cell phenotypes, and peripheral CD4+ T-cell associated total, integrated and 2-long terminal repeat HIV DNA species. [AIDS] Abstract Analysis of Protein Kinase C Theta Inhibitors for the Control of HIV-1 Replication in Human CD4+ T Cells Reveals an Effect on Retrotranscription in Addition to Viral Transcription Scientists found that protein kinase C theta (PKCθ) activity increased viral replication, but also that HIV-1 induced higher activation of PKCθ in infected CD4+ T cells, creating a feedback loop. [Biochem Pharmacol] Abstract Don’t forget to subscribe to our sister publications: Human Immunology News and Immune Regulation News! |