Immunology of Infectious Disease News Volume 4.09 | Mar 9 2016

Broad Defects in the Energy Metabolism of Leukocytes Underlie Immunoparalysis in Sepsis
By transcriptional and metabolic profiling of human patients with sepsis, investigators found that a shift from oxidative phosphorylation to aerobic glycolysis was an important component of initial activation of host defense. Blocking metabolic pathways with metformin diminished cytokine production and increased mortality in systemic fungal infection in mice. [Nat Immunol] Abstract

Innate Myeloid Cell TNFR1 Mediates First Line Defense against Primary Mycobacterium tuberculosis Infection
Researchers assessed the contribution of TNFR1 pathway from innate myeloid versus T cells. Absence of TNFR1 specifically on myeloid cells recapitulated the uncontrolled M. tuberculosis infection seen in fully TNFR1 deficient mice, with increased bacterial burden, exacerbated lung inflammation, and rapid death. [Sci Rep] Full Article

Eliminating Legionella by Inhibiting BCL-XL to Induce Macrophage Apoptosis
Researchers identified a host-directed therapeutic approach to eliminate intracellular Legionella infections. They demonstrated that the genetic deletion, or pharmacological inhibition, of the host cell pro-survival protein BCL-XL induces intrinsic apoptosis of macrophages infected with virulent Legionella strains, thereby abrogating Legionella replication. [Nat Microbiol] Abstract | Press Release

HIV

Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody
Antibodies with ontogenies from V_H1-2 or V_H1-46-germline genes dominated the broadly neutralizing response against the CD4-binding site on HIV-1. Scientists defined with longitudinal sampling from time-of-infection the development of a V_H1-46-derived antibody lineage that matured to neutralize 90% of HIV-1 isolates. [Cell] Abstract | Graphical Abstract | Press Release

Tumor-Necrosis Factor Impairs CD4⁺ T Cell–Mediated Immunological Control in Chronic Viral Infection
In prototypic models of chronicity—infection with human immunodeficiency virus or lymphocytic choriomeningitis virus—researchers used transcriptome-based modeling to reveal that CD4⁺ T cells were co-exposed not only to multiple inhibitory signals but also to tumor-necrosis factor. [Nat Immunol]
Abstract | Press Release

Macrophages Sustain HIV Replication In Vivo Independently of T Cells
Investigators addressed the role of macrophages in HIV infection by first analyzing monocytes isolated from viremic patients and patients undergoing antiretroviral treatment. They were unable to find viral DNA or viral outgrowth in monocytes isolated from peripheral blood. [J Clin Invest] Full Article | Press Release

Elimination of HIV-1 Genomes from Human T-Lymphoid Cells by CRISPR/Cas9 Gene Editing
Scientists employed an RNA-guided CRISPR/Cas9 DNA editing system to precisely remove the entire HIV-1 genome spanning between 5′ and 3′ LTRs of integrated HIV-1 proviral DNA copies from latently infected human CD4⁺ T-cells. [Sci Rep] Full Article

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‘Black Death’ Offers Clues to Battling HIV and Hepatitis C Centuries Later
The Black Death left genetic clues that now may aid a University of Cincinnati researcher in treating HIV patients co-infected with hepatitis C using an anti-retroviral drug therapy. Kenneth Sherman, MD, PhD, will look at the blood samples of nearly 3,000 patients, primarily individuals with hemophilia, who were exposed to HIV during the early 1980s and late 1990s, to see if an inherited genetic variant that protects against HIV might also help prevent injury from hepatitis C and other liver diseases. [University of Cincinnati] Press Release

RedHill Biopharma Reports Successful Final Results of Phase III Study with RHB-105 for H. pylori Infection
RedHill Biopharma Ltd. announced successful final results from the first Phase III clinical study with RHB-105 for the eradication of H. pylori. The study successfully met its primary endpoint of superiority over historical standard-of-care eradication rate levels of 70%, with high statistical significance. [RedHill Biopharma Ltd.] Press Release

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Senior Scientist – Immunology and Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Immune Responses to Vaccines (Boston Children’s Hospital)

Postdoctoral Fellowship – Mucosal Infection and Inflammation Center (Linköping University)

Principal Scientist – Infectious Disease (Janssen Pharmaceutica N.V.)

Postdoctoral Fellow – Drug Delivery for HIV (Northwestern University)

Principal Investigators – Infectious Diseases (CCID)

Administrative Head – Vaccine and Infectious Disease (Fred Hutchinson Cancer Research Center)

Senior Scientist – Immunology (Bavarian Nordic GmbH)

Global Medical Leader – Infectious Diseases (F. Hoffmann-La Roche)

Research Technician I – HIV Vaccine Trials (Fred Hutchinson Cancer Research Center)

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