Immunology of Infectious Disease News Volume 3.43 | Nov 18 2015

Inflammation Drives Thrombosis after Salmonella Infection via CLEC-2 on Platelets
Using a mouse model of systemic Salmonella Typhimurium infection, researchers determined that inflammation in tissues triggers thrombosis within vessels via ligation of C-type lectin–like receptor-2 (CLEC-2) on platelets by podoplanin exposed to the vasculature following breaching of the vessel wall. [J Clin Invest]
Full Article | Press Release

Poorly Cross-Linked Peptidoglycan in MRSA Due to mecA Induction Activates the Inflammasome and Exacerbates Immunopathology
Researchers showed that the protein conferring β-lactam antibiotic resistance, penicillin-binding protein 2A, directly contributes to pathogenicity during methicillin-resistant S. aureus (MRSA) infection. MecA induction led to a reduction in peptidoglycan cross-linking that allows for enhanced degradation and detection by phagocytes, resulting in robust IL-1β production. [Cell Host Microbe] Full Article | Graphical Abstract | Press Release

Adenoviral Vector Vaccination Induces a Conserved Program of CD8⁺ T Cell Memory Differentiation in Mouse and Man
Investigators addressed the transcriptional regulation of divergent CD8⁺ T cell memory pools induced by an adenovector encoding a model antigen. They observed transcriptional profiles that mimic those following infection with persistent pathogens, murine and human cytomegalovirus. [Cell Rep]
Full Article | Graphical Abstract

Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection
Using a murine model of recurrent S. aureus peritonitis, researchers demonstrated that prior exposure to S. aureus enhanced IFNγ responses upon subsequent infection, while adoptive transfer of S. aureus antigen-specific Th1 cells was protective in naïve mice. [PLoS Pathog] Full Article | Press Release | Video

miR-150 Regulates Differentiation and Cytolytic Effector Function in CD8⁺ T Cells
The authors showed that in the absence of the microRNA miR-150, CD8⁺ T cells fail to undergo robust expansion and differentiation into short-lived terminal effector cells in response to primary infection with Listeria monocytogenes or Vaccinia virus. [Sci Rep] Full Article

Lower Expression of GATA3 and T-Bet Correlates with Downregulated IL-10 in Severe Falciparum Malaria
Researchers previously demonstrated downregulated levels of interleukin (IL)-10 in severe falciparum malaria. Here, they investigated transcriptional regulation of IL-10 in severe malaria. [Clin Transl Immunol] Full Article

HIV

Interleukin-21 Combined with ART Reduces Inflammation and Viral Reservoir in SIV-Infected Macaques
Scientists investigated the effects of IL-21 administration on both inflammation and virus persistence in antiretroviral therapy (ART)-treated, SIV-infected rhesus macaques (RMs). Compared with SIV-infected animals only given ART, SIV-infected RMs given both ART and IL-21 showed improved restoration of intestinal Th17 and Th22 cells and a more effective reduction of immune activation in blood and intestinal mucosa, with the latter maintained through eight months after ART interruption. [J Clin Invest] Full Article | Press Release

Gut-Resident Lactobacillus Abundance Associates with IDO1 Inhibition and Th17 Dynamics in SIV-Infected Macaques
Scientists observed a specific depletion of gut-resident Lactobacillus during acute and chronic simian immunodeficiency virus (SIV) infection of rhesus macaques, which was also seen in early HIV-infected humans. This depletion in rhesus macaques correlated with increased indoleamine 2,3-dioxygenase 1 (IDO1) activity and Th17 loss. [Cell Rep] Full Article | Graphical Abstract

Targeting HIV Reservoir in Infected CD4 T Cells by Dual-Affinity Re-Targeting Molecules (DARTs) that Bind HIV Envelope and Recruit Cytotoxic T Cells
Investigators designed and evaluated HIV envelope protein (Env)-specific DARTs derived from known antibodies recognizing diverse Env epitopes with or without broadly neutralizing activity. [PLoS Pathog] Full Article | Press Release

CRISPR/gRNA-Directed Synergistic Activation Mediator (SAM) Induces Specific, Persistent and Robust Reactivation of the HIV-1 Latent Reservoirs
The authors present a novel catalytically-deficient Cas9-synergistic activation mediator technology to selectively, potently and persistently reactivate the HIV-1 latent reservoirs. [Sci Rep] Full Article

Analysis of T Cell Responses to Chimpanzee Adenovirus Vectors Encoding HIV Gag–Pol–Nef Antigen
Chimpanzee adenoviruses (chAd)3 and chAd63 were used to deliver an HIV gag, pol and nef transgene. ELISpot analysis of T cell responses in mice showed that both chAd vectors were able to induce an immune response to Gag and Pol peptides but that only the chAd3 vector induced responses to Nef peptides. [Vaccine] Full Article | Press Release

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Immune Interactions with Pathogenic and Commensal Fungi: A Two-Way Street
Investigators review themes and controversies that are currently shaping investigation of antifungal immunity (primarily to Candida and Aspergillus) and examine the emerging field of the role of fungi in the gut microbiome. [Immunity] Full Article

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Protagen and Mikrogen Agree on Co-Development of Novel Lyme Disease Markers
Protagen AG and Mikrogen GmbH agreed on a co-development program for a new diagnostic assay to distinguish between previously infected, seropositive individuals, from newly infected patients with active Lyme disease. [Protagen AG] Press Release

FDA Approves New Treatment for HIV
The U.S. Food and Drug Administration approved Genvoya as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients 12 years of age and older. [U.S. Food and Drug Administration] Press Release

AbbVie Announces High Sustained Virologic Response Rates in Phase II Studies with Pan-Genotypic, Investigational Regimen in Patients with Chronic Hepatitis C
AbbVie announced data from the SURVEYOR studies of its investigational hepatitis C virus (HCV) regimen, ABT-493, an NS3/4A protease inhibitor, and ABT-530, an NS5A inhibitor, that show high rates of sustained virologic response at 12 weeks post-treatment in non-cirrhotic patients with chronic HCV infection. [AbbVie Inc.] Press Release

Transgene Announces Dosing of First Patient with TG1050 for Treatment of Chronic Hepatitis B Infection
Transgene SA announced that the first patient has been dosed in a clinical trial with its immunotherapy product candidate TG1050 for the treatment of chronic hepatitis B virus infection. [Transgene SA] Press Release

HHS to Procure Two Inhalational Anthrax Treatments for National Supply
To better protect public health in an anthrax attack, the U.S. Department of Health and Human Services’ (HHS) Office of the Assistant Secretary for Preparedness and Response will add two types of anthrax antitoxin drugs for the Strategic National Stockpile as options to treat inhalational anthrax. [U.S. Department of Health & Human Services] Press Release

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NEW Faculty Position – Infectious Diseases (Washington University School of Medicine)

NEW Postdoctoral Position – Immunology/Vaccinology/Bioinformatics (Boston Children’s Hospital and Harvard Medical School)

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

Postdoctoral Fellow – Optical Trapping of HIV (University of Michigan Ann Arbor)

Postdoctoral Fellow – HIV/SIV Immunology (Beth Israel Deaconess Medical Center)

Postdoctoral Fellow – Meningeal Immunity in Healthy and Injured CNS (University of Virginia)

Postdoctoral Position – Immune Responses in Influenza Virus Infection (National Institute of Allergy and Infectious Diseases)

Lab Aide I – Immune Responses to Herpes Simplex Virus (Fred Hutchinson Cancer Research Center)

Postdoctoral Scientist – Membrane Structural Biology and Virus-Host Interactions (Harbin Institute of Technology)

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