Volume 1.09 | May 15

Immunology of Infectious Disease News 1.09 May 15, 2013
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TOP STORY
Single Naive CD4+ T Cells from a Diverse Repertoire Produce Different Effector Cell Types during Infection
A naive CD4+ T cell population specific for a microbial peptide: major histocompatibility complex II ligand typically consists of about 100 cells, each with a different T cell receptor. Following infection, this population produces a consistent ratio of effector cells that activate microbicidal functions of macrophages or help B cells make antibodies. Researchers studied the mechanism that underlies this division of labor by tracking the progeny of single naive T cells. [Cell] Abstract | Graphical Abstract

How Ex Vivo Models Drive Progress in HIV Research: Read the Research Profiles

PUBLICATIONS (Ranked by impact factor of the journal)

Bacterial-Derived Uracil as a Modulator of Mucosal Immunity and Gut-Microbe Homeostasis in Drosophila
Investigators showed that bacterial-derived uracil acts as a ligand for dual oxidase-dependent reactive oxygen species generation in Drosophila gut and that the uracil production in bacteria causes inflammation in the gut. The acute and controlled uracil-induced immune response is required for efficient elimination of bacteria, intestinal cell repair, and host survival during infection of nonresident species. [Cell]
Abstract | Graphical Abstract

Safety and Immunogenicity of a Novel Multivalent OspA Vaccine against Lyme Borreliosis in Healthy Adults: A Double-Blind, Randomized, Dose-Escalation Phase I/II Trial
The authors investigated the safety and immunogenicity of adjuvanted and non-adjuvanted vaccines containing protective epitopes from Borrelia species outer surface protein A (OspA) serotypes in healthy adults. [Lancet Infect Dis] Abstract | Press Release

Dual Function of the McaS Small RNA in Controlling Biofilm Formation
Researchers demonstrated that multicellular adhesive (McaS) activates synthesis of the exopolysaccharide ß-1,6 N-acetyl-D-glucosamine (PGA) by binding the global RNA-binding protein CsrA, a negative regulator of pgaA translation. The McaS RNA bears at least two CsrA-binding sequences, and inactivation of these sites compromises CsrA binding, PGA regulation, and biofilm formation. [Gene Dev] Abstract | Press Release

Indoleamine 2,3-Dioxygenase Activity Contributes to Local Immune Suppression in the Skin Expressing Human Papillomavirus Oncoprotein E7
Investigators showed that indoleamine 2, 3-dioxygenase (IDO) 1, an IFN-γ inducible immunoregulatory molecule, is more highly expressed by langerin-ve dermal dendritic cells from keratin-14 promoter (K14E7) skin than nontransgenic control skin. Furthermore, inhibiting IDO activity using 1-D/L-methyl tryptophan promotes K14E7 skin graft rejection. [J Invest Dermatol] Abstract

STAT4-Dependent and Independent Th2 Responses Correlate with Protective Immunity against Lung Infection with Pneumocystis murina
Although it is clear that the loss of CD4+ T cells is a predisposing factor for the development of Pneumocystis pneumonia, specific Th mechanisms mediating protection are not well understood. Th1, Th2, and Th17 responses have each been implicated in protective responses during infection. As STAT4 may promote Th1 and Th17 development, yet antagonize Th2 development, scientists investigated its role in Pneumocystis murina host defense. [J Immunol] Abstract

HIV

Vaccine-Induced Plasma IgA Specific for the C1 Region of the HIV-1 Envelope Blocks Binding and Effector Function of IgG
Scientists investigated the hypothesis that IgA could attenuate the protective effect of IgG responses through competition for the same envelope (Env) binding sites. They report that Env-specific plasma IgA/IgG ratios are higher in infected than in uninfected vaccine recipients in RV144. [Proc Natl Acad Sci USA]
Abstract | Press Release

Impaired CD4+ T Cell Stimulation of NK Cell Anti-Fibrotic Activity may Contribute to Accelerated Liver Fibrosis Progression in HIV/Hepatitis C Virus Patients
The authors showed that CD4+ T cells are able to stimulate anti-fibrotic natural killer (NK) cell activity via interleukin-2 mediated up-regulation of NKG2D. Human immunodeficiency virus (HIV) induced loss of CD4+ T cells together with an impaired activity of CD4+ T cells may contribute to accelerate progression of liver fibrosis observed in co-infection. [J Hepatol] Abstract

Altered T Cell Subsets in HIV-1 Natural Viral Suppressors (Elite Controllers) with Hepatitis C Infection
Scientists investigated T cell phenotypic changes in association with hepatitis C virus (HCV) infection. Natural viral suppressors (NVS) without HCV and normal controls had similar T cell phenotypes. However, NVS with HCV had lower naive cell proportions compared to NVS without HCV. [AIDS] Abstract

Consensus HIV-1 FSU-A Integrase Gene Variants Electroporated into Mice Induce Polyfunctional Antigen-Specific CD4+ and CD8+ T Cells
Multiparametric FACS demonstrated that CD8+ and CD4+ T cells of gene-immunized mice stimulated with integrase-derived peptides secreted IFN-γ, IL-2, and TNF-α. The multi-cytokine responses of CD8+ and CD4+ T-cells correlated with the loss of in vivo activity of the luciferase reporter gene co-delivered with pVaxIN plasmids. [PLoS One] Full Article

Lack of Correlation between the Size of HIV Proviral DNA Reservoir and the Level of Immune Activation in HIV-Infected Patients with a Sustained Undetectable HIV Viral Load for Ten Years
The persistence of HIV residual replication in patients with an undetectable plasma viral load (pVL) may limit immune recovery and facilitate inflammation-induced comorbidities. Researchers aimed to evaluate any correlation between immune restoration and intracellular HIV-DNA in cART-treated patients with a sustained undetectable pVL. [J Clin Virol] Abstract

Histamine Enhances HIV-1-Induced Modulation of Dendritic Cells to Skew Naïve T Cell Differentiation toward Regulatory T Cells
The authors investigated histamine-assisted HIV-1 modulation of dendritic cell (DC) functions. Histamine and HIV-1 showed a synergistic role in induction of interleukin (IL)-10; histamine inhibited HIV-1-induced IL-12 production from monocyte-derived DCs (MDDCs); notably, histamine augmented HIV-1-induced MDDC functional polarization and skewed naïve T cell differentiation toward regulatory T cells. [Virology] Abstract

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REVIEWS

Translation Inhibition and Metabolic Stress Pathways in the Host Response to Bacterial Pathogens
A flurry of recent studies has now uncovered a role for host translation inhibition in innate immune surveillance and the detection of bacterial pathogens. Here, the authors present the main findings from these studies and discuss whether translation inhibition is an alarm signal that directly drives innate immune responses to bacterial pathogens, or rather one component of a more general metabolic stress response to infection. [Nat Rev Microbiol] Abstract

Multiple Sclerosis: Autoimmunity and Viruses
This review explores two new aspects of the involvement of viruses in multiple sclerosis pathogenesis. The first aspect is the complex interactions between viruses. The second aspect is the proposal of a mechanism by which autoreactive T cells are able to escape thymic selection and potentially recognize self and a pathogen. [Curr Opin Rheumatol] Abstract

Visit our reviews page to see a complete list of reviews in the infectious disease research field.

SCIENCE NEWS
Sangamo BioSciences Presents Clinical Data Demonstrating HIV Reservoir Reduction in HIV-Infected Subjects Treated with ZFP Therapeutic®, SB-728-T
Sangamo BioSciences, Inc. announced the presentation of new clinical data from its program to develop a ZFP Therapeutic® for HIV/AIDS.  The data demonstrates that SB-728-T treatment results in a reduction in the HIV reservoir in HIV-infected subjects. [Press release from Sangamo Biosciences, Inc. discussing research presented at the 16th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT), Salt Lake City] Press Release

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INDUSTRY NEWS

GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant], Merck’s HPV Vaccine, Available to Developing Countries through UNICEF Tender
Merck announced that the company has been awarded a significant portion of the UNICEF human papillomavirus (HPV) vaccine tender, and will provide sustained supply of GARDASIL® to GAVI-eligible countries. [Merck & Co., Inc.] Press Release

Cell Medica Announces Treatment of First Pediatric Patient in Early Stage Clinical Trial of Cytovir ADV
Cell Medica announced the treatment of the first patient in the ASPIRE Trial, an early stage Phase I/II clinical study investigating the safety and efficacy of CytovirTM ADV for the treatment of adenovirus infections in immunosuppressed pediatric patients following bone marrow transplantation. [Cell Medica] Press Release

Jean-Laurent Casanova Appointed HHMI Investigator

Jean-Laurent Casanova, senior attending physician at The Rockefeller University Hospital and head of the St. Giles Laboratory of Human Genetics of Infectious Diseases, has been named one of 27 new investigators with the Howard Hughes Medical Institute (HHMI). Casanova’s research centers on identifying genetic mutations that predispose individuals to specific pathogens, in order to understand why some children get sick during the course of infection while others exposed to the same pathogen do not. [The Rockefeller University]
Press Release

POLICY NEWS

National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

EVENTS

NEW Infectious Diseases World Summit 2013
July 8-10, 2013
Boston, United States

Visit our
events page to see a complete list of events in the infectious disease community.

JOB OPPORTUNITIES

NEW Canada Research Chair – Immunology of Chronic Viral Infections & Immune Senescence (Dalhousie University Faculty of Medicine)

Postdoctoral Fellow – Stem Cell and Cancer Biology (Johns Hopkins University School of Medicine)

Postdoctoral Research Associate – Immunologist (University of Edinburgh)

Postdoctoral Fellow – Host Pathogen Interaction (Columbia Initiative for Systems Biology / Columbia University)


Postdoctoral Position – Immunology and Vaccinology (Université de Liège)

Postdoctoral Position – Immunology (New York University)

Postdoctoral Scientist – Infection by Influenza Virus (National Institute for Medical Research, Medical Research Council)

Assistant Scientist – Immunodeficiency Virus Replication (University of Wisconsin – Madison Primate Research Center)


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