Immunology of Infectious Disease News Volume 4.48 | Dec 7 2016

TOP STORY

Immunometabolic Pathways in BCG-Induced Trained Immunity

Researchers showed that Bacillus Calmette-Guerin (BCG) induction of trained immunity in monocytes is accompanied by a strong increase in glycolysis and, to a lesser extent, glutamine metabolism, both in an in-vitro model and after vaccination of mice and humans. [Cell Rep] Full Article | Graphical Abstract | Press Release

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CD8⁺ T Cells Induce Fatal Brainstem Pathology during Cerebral Malaria via Luminal Antigen-Specific Engagement of Brain Vasculature

At the peak of experimental cerebral malaria, scientists revealed using intravital two-photon microscopy that myelomonocytic cells and parasite-specific CD8⁺ T cells associated primarily with the luminal surface of CNS blood vessels. Myelomonocytic cells participated in the removal of parasitized red blood cells from cerebral blood vessels, but were not required for the disease. [PLoS Pathog] Full Article | Press Release

Macrophage Colony Stimulating Factor Derived from CD4⁺ T Cells Contributes to Control of a Blood-Borne Infection

Researchers showed that myeloid expansion during Plasmodium chabaudi infection is dependent upon both CD4⁺ T cells and the cytokine Macrophage Colony Stimulating Factor (MCSF). Single-cell RNA-Seq analysis on antigen-experienced T cells revealed robust expression of Csf1, the gene encoding MCSF, in a sub-population of CD4⁺ T cells with distinct transcriptional and surface phenotypes. [PLoS Pathog] Full Article

IL-21-Dependent Expansion of Memory-Like NK Cells Enhances Protective Immune Responses against Mycobacterium tuberculosis

Using a mouse model of tuberculosis infection, investigators found that interferon-gamma producing CD3⁻NKp46⁺CD27⁺KLRG1⁺ memory-like natural killer (NK) cells develop during Bacille Calmette–Guérin vaccination, expand, and provide protection against challenge with M. tuberculosis. [Mucosal Immunol] Full Article

Immune-Responsiveness of CD4⁺ T Cells during Streptococcus suis Serotype 2 Infection

The authors aimed to evaluate modulation of T cell activation during S. suis infection and the role of dendritic cells in this response. S. suis-stimulated total mouse splenocytes readily produced TNF-α, IL-6, IFN-γ, CCL3, CXCL9, and IL-10. [Sci Rep] Full Article

Mycobacterium tuberculosis EsxH Inhibits ESCRT-Dependent CD4⁺ T-Cell Activation

Researchers showed that endosomal sorting complex required for transport (ESCRT) is required for optimal antigen processing; correspondingly, overexpression and loss-of-function studies demonstrated that EsxH inhibited the ability of macrophages and dendritic cells to activate M. tuberculosis antigen-specific CD4⁺ T cells. [Nat Microbiol] Abstract

HIV

Immune Activation Influences SAMHD1 Expression and Vpx-Mediated SAMHD1 Degradation during Chronic HIV-1 Infection

Scientists report activated CD4⁺ T cells without SAMHD1 expression were severely reduced, and SAMHD1 in CD4⁺ T cells became susceptible to SIV-Vpx mediated degradation during chronic HIV-1 infection, which was absent from uninfected donors. [Sci Rep] Full Article

First Phase I Human Clinical Trial of a Killed Whole-HIV-1 Vaccine: Demonstration of its Safety and Enhancement of Anti-HIV Antibody Responses

Genetically modified and killed whole-HIV-1 vaccine, SAV001, was well tolerated with no serious adverse events. HIV-1_NL4-3-specific PCR showed neither evidence of vaccine virus replication in the vaccine virus-infected human T lymphocytes in vitro nor in the participating volunteers receiving SAV001 vaccine. [Retrovirology] Full Article

Filariae-Retrovirus Co-Infection in Mice Is Associated with Suppressed Virus-Specific IgG Immune Response and Higher Viral Loads

To test whether helminths affect the outcome of a viral infection the authors set up a filarial/retrovirus co-infection model in C57BL/6 mice. Although Friend virus (FV) infection altered the Litomosoides sigmodontis-specific immunoglobulin response towards a type I associated IgG2 isotype in co-infected mice, control of L. sigmodontis infection was not affected by a FV-superinfection. [PLoS Negl Trop Dis] Full Article

Targeting the Rhesus Macaque TRIM5α Gene to Enhance the Susceptibility of CD4⁺ T Cells to HIV-1 Infection

Researchers targeted the tripartite motif 5 alpha (TRIM5α) gene of rhesus macaques using the transcription activator-like effector nuclease to study the effect on HIV-1 infection. [Arch Virol] Abstract

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Fate of Microglia during HIV-1 Infection: From Activation to Senescence?

The authors first describe microglial origins and function in the normal central nervous system, and the changes that occur during aging. They then critically discuss how HIV-1 infection and exposure to viral proteins such as Tat and gp120 affect various aspects of microglial homeostasis including activation, cellular metabolism and cell cycle regulation, through pathways implicated in cellular stress responses including p38 mitogen-activated protein kinase and nuclear factor κB. [Glia] Abstract

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ABIVAX Provides Update on Clinical Development Program for ABX464 for Functional Cure of Patients with HIV-Infection

ABIVAX provides a clinical update on the clinical development program for ABX464, ABIVAX’s first-in-class drug candidate for achieving a functional cure in patients with HIV/AIDS. [ABIVAX] Press Release

Arsanis Receives FDA Fast Track Designation for ASN100 for the Prevention of Staphylococcus aureus Pneumonia

Arsanis, Inc. announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to ASN100 for the prevention of S. aureus pneumonia in mechanically ventilated patients who are at high risk for S. aureus pneumonia. [Arsanis, Inc.] Press Release

Stopgap Spending Bill Leaves US Scientists in Limbo

In what has become a year-end tradition in Washington DC, the US Congress is getting ready to approve a stopgap spending measure before it adjourns for the holidays. Many researchers are more worried about what might come after this temporary funding extension, if it is approved. When president-elect Donald Trump takes office, Republicans will control the White House and both houses of Congress — and their science priorities are very different from those of outgoing President Barack Obama, a Democrat. [Nature News] Editorial

Mexico Proposal to Ban Human-Embryo Research Would Stifle Science

Researchers are waiting to see whether Mexico’s legislature will approve an amendment to the national health law that would ban experiments with human embryos. The amendment is intended to regulate assisted reproduction, including the payment of surrogate mothers, donations to egg and sperm banks and the fertilization of more than three eggs at a time. But it would also ban the creation of human embryos for any purpose except reproduction and any research with existing human embryos. [Nature News] Editorial

CRISPR Heavyweights Battle in US Patent Court

Berkeley and its rival, the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, are each vying for the intellectual property underlying CRISPR–Cas9, which is adapted from a system that bacteria use to fend off viruses. During the hearing the US Patent and Trademark Office judges challenged Berkeley’s central claim: that once its researchers demonstrated that CRISPR–Cas9 could be used to edit DNA in bacteria, any reasonably skilled person could have adapted the technique for use in more complex cells. [Nature News] Editorial

NEW Association of Medical Microbiology and Infectious Disease Canada (AMMI) Annual Conference 2017
May 3-6, 2016
Toronto, Canada

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NEW Postdoctoral Research Fellow – HIV Immunotherapy (Fred Hutchinson Cancer Research Center)

NEW Postdoctoral Position – Pre-Clinical In Vivo Studies and Immunology (German Cancer Research Center)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Research Fellow – CAR T Cell Therapy for HIV Infection (Fred Hutchinson Cancer Research Center)

Postdoctoral Research Fellow – Viral Infection Modeling (Fred Hutchinson Cancer Research Center)

Postdoctoral Position – Immunology of HIV-1 and Cancer (University of Alabama at Birmingham)

Postdoctoral Research Scientist – Infection (Rush University Medical Center)

Research Fellow – HIV Research (Dana-Farber Cancer Institute)

Postdoctoral Fellow – Immunology of Chronic HBV Infection (F. Hoffmann-La Roche)

Faculty Position – Senior Immunologist (Fred Hutchinson Cancer Research Center)

Postdoctoral Research Fellow – Quantitative Infectious Disease Methods (Fred Hutchinson Cancer Research Center)

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