Volume 3.34 | Sep 9

Immunology of Infectious Disease News 3.34 September 9, 2015
Immunology of Infectious Disease News
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Immune Cells Take Cue from Animal Kingdom: Together, Everyone Achieves More
Researchers reveal, for the first time, how immune cells work together to get to their final destination – the site of an injury or infection. They discovered that cells called neutrophils – the “first responders” of the immune system – are the key. [Press release from the University of Rochester Medical Center discussing online publication in Science] Press Release | Abstract | Video
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PUBLICATIONS (Ranked by impact factor of the journal)
Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses
To characterize the gene expression variation that underlies distinct infection outcomes and monitor infection phenotypes, scientists developed an experimental system that combines single-cell RNA-seq with fluorescent markers. Probing the responses of individual macrophages to invading Salmonella, they found that variation between individual infected host cells is determined by the heterogeneous activity of bacterial factors in individual infecting bacteria. [Cell] Abstract | Graphical Abstract

IFN-γ Induction by Neutrophil-Derived IL-17A Homodimer Augments Pulmonary Antibacterial Defense
The role of interleukin-17A (IL-17A) in host defense against Legionella pneumophila remains elusive. Researchers found that neutrophils produce IL-17A homodimer during L. pneumophila infection, and hematopoietic cell-derived IL-17A is known to be important for bacterial clearance. [Mucosal Immunol] Abstract

CD4+ T-Cell Survival in the GI Tract Requires Dectin-1 during Fungal Infection
Scientists showed that Dectin-1 is essential for driving fungal-specific CD4+ T-cell responses in the gastrointestinal (GI) tract. Loss of Dectin-1 resulted in abrogated dendritic cell responses in the mesenteric lymph nodes and defective T-cell co-stimulation, causing substantial increases in CD4+ T-cell apoptosis and reductions in the cellularity of GI-associated lymphoid tissues. [Mucosal Immunol] Full Article

Trypanosoma cruzi Infection Imparts a Regulatory Program in Dendritic Cells and T Cells via Galectin-1–Dependent Mechanisms
Researchers showed that galectin-1 (Gal-1) functions as a negative regulator to limit host-protective immunity following intradermal infection with T. cruzi. Concomitant with the upregulation of immune inhibitory mediators, including IL-10, TGF-β1, IDO, and programmed death ligand 2, T. cruzi infection induced an early increase of Gal-1 expression in vivo. [J Immunol] Abstract


Magnitude and Kinetics of CD8+ T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point
Investigators screened high-risk uninfected women twice a week for plasma HIV RNA and identified 12 hyperacute infections. Onset of viremia elicited a massive HIV-specific CD8+ T cell response, with limited bystander activation of non-HIV memory CD8+ T cells. [Immunity] Abstract

Sequence-Specific Activation of the DNA Sensor cGAS by Y-Form DNA Structures as Found in Primary HIV-1 cDNA
Researchers found that unpaired DNA nucleotides flanking short base-paired DNA stretches, as in stem-loop structures of single-stranded DNA derived from human immunodeficiency virus type 1 (HIV-1), activated the type I interferon–inducing DNA sensor cGAS in a sequence-dependent manner. [Nat Immunol]
Abstract | Press Release

The Local Environment Orchestrates Mucosal Decidual Macrophage Differentiation and Substantially Inhibits HIV-1 Replication
Scientists showed, by using freshly purified decidual macrophages and ex vivo human decidual explants, that the local decidual environment influences decidua basalis differentiation and naturally protects these cells from HIV-1 infection. [Mucosal Immunol] Abstract

Impairment of T Cell Development and Acute Inflammatory Response in HIV-1 Tat Transgenic Mice
Researchers addressed whether HIV-1 Tat could affect T cell development and acute inflammatory response by generating a transgenic mouse expressing Tat in lymphoid tissue. Tat-Tg mice showed thymus atrophy and the maturation block from DN4 to DP thymic subpopulations, resulting in CD4+ and CD8+ T cells depletion in peripheral blood. [Sci Rep] Full Article

Increased Frequency of Circulating Tc22/Th22 Cells and Polyfunctional CD38 T Cells in HIV-Exposed Uninfected Subjects
Innate factors like IL-22 exert gut mucosal protection and polyfunctional T cells have been associated with low progression in HIV infection; therefore, investigators evaluated the frequencies of CD4+ and CD8+ T cell-secreting cytokines, including Tc22/Th22 cells and polyfunctional T cells in HIV-1-exposed uninfected individuals, their HIV-1-infected partners and healthy controls. [Sci Rep] Full Article

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The March toward Malaria Vaccines
The authors focus on four approaches to malaria vaccines: a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle; whole sporozoite vaccines aimed at Pf pre-erythrocytic stages; prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages; and recombinant protein with adjuvant vaccines aimed at Pf and P. vivax sexual erythrocytic and mosquito stages. [Vaccine] Abstract

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$1.85 Million NIH Grant Funds Project to Study Virus Interaction with the Immune System and Identify Poxvirus Threats
The National Institutes of Health (NIH) are funding a Kansas State University research project that is looking at viruses that have the potential to be the next smallpox as well as an effective weapon against cancer. [Kansas State University] Press Release

RedHill Biopharma Announces Standard-of-Care Eradication Data from the RHB-105 Phase III Study Further Supporting the Study’s Positive Results
RedHill Biopharma Ltd. announced additional supportive data from the first Phase III study with RHB-105 for eradication of Helicobacter pylori. Results from the subsequent open-label treatment of patients in the placebo arm with standard-of-care (SoC) therapy for persistent H. pylori infection demonstrated a 63% eradication rate with SoC, compared to the previously reported 89.4% eradication rate demonstrated in the RHB-105 arm of the controlled study. [RedHill Biopharma Ltd.] Press Release

Inovio Pharmaceuticals Announces First Patient Dosed with Universal HIV Vaccine
Inovio Pharmaceuticals, Inc. announced that the first patient has been dosed in a Phase I trial to evaluate safety and tolerability of PENNVAX®-GP, Inovio’s “universal” DNA vaccine for HIV. [Inovio Pharmaceuticals, Inc.] Press Release

Basilea Announces Development of Inhaled Dosage Form of Its Gram-Negative Antibiotic BAL30072 as Part of European iABC Program
Basilea Pharmaceutica Ltd. announced that an inhaled formulation of its antibiotic BAL30072 will be developed as part of a new Europe-wide program focusing on new antibiotics that could improve the lives of patients with cystic fibrosis and bronchiectasis. [Basilea Pharmaceutica Ltd.] Press Release

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New Game, New Rules – Limiting the Risks of Biological Engineering
“Gain-of-function” research involves creating more contagious forms of highly pathogenic avian flu in the laboratory to learn what genetic changes are required for a flu strain to cause a pandemic. The main question is whether the scientific knowledge provided by making flu strains more contagious outweighs the risk of a lab accident or deliberate misuse that could lead to an outbreak of these enhanced viruses. [Foreign Affairs] Editorial | Press Release

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)
NEW Keystone Symposium – Systems Immunology: From Molecular Networks to Human Biology
January 10-14, 2016
Big Sky, United States

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NEW Assistant Professor – Immunology (Erasmus University Medical Center)

NEW Postdoctoral Scientist – Host-Pathogen Interactions (Cedars-Sinai)

NEW Postdoctoral Research Associate – Molecular Immunology (GlaxoSmithKline)

Postdoctoral Position – Immunology and Virology (Herman B Wells Center for Pediatric Research)

Faculty Positions – Virology (NYU School of Medicine)

Postdoctoral Scientist – Innate and Adaptive Immune Response to S. Aureus Infection (Cedars-Sinai)

PhD Positions – Infection Biology and Immunology (ZIBI Graduate School)

Postdoctoral Position – HIV Vaccine Immunology (Dana-Farber Cancer Institute)

Postdoctoral Fellow – Molecular Microbiology/Immunology (The University of Tennessee)

Postdoctoral Fellowship – Viral Immunology (Emory University)

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