Immunology of Infectious Disease News Volume 6.03 | Jan 24 2018

TOP STORY

Tumor-Derived Exosomes Antagonize Innate Antiviral Immunity

Investigators found that, via tumor-derived exosomes (TEXs), cancers were able to transfer activated epidermal growth factor receptor (EGFR) to host macrophages and thereby suppress innate antiviral immunity. Screening of the human kinome identified the kinase MEKK2 in macrophages as an effector of TEX-delivered EGFR that negatively regulated the antiviral immune response. [Nat Immunol] Abstract

(Ranked by impact factor of the journal)

Latent HIV Reservoirs Exhibit Inherent Resistance to Elimination by CD8⁺ T Cells

The authors showed that treating CD4⁺ T cells from antiretroviral therapy-treated individuals with combinations of potent latency-reversing agents and autologous CD8⁺ T cells consistently reduced cell-associated HIV DNA, but failed to deplete replication-competent virus. These CD8⁺ T cells recognized and potently eliminated CD4⁺ T cells that were newly infected with autologous reservoir virus, ruling out a role for both immune escape and CD8⁺ T cell dysfunction. [J Clin Invest] Full Article

Mannose Receptor 1 Restricts HIV Particle Release from Infected Macrophages

Researchers identified human mannose receptor 1 (hMRC1) as an antiviral factor that inhibits virus release through a bone marrow stromal antigen 2-like mechanism. Virions produced in the presence of hMRC1 accumulated in clusters at the cell surface but were fully infectious. [Cell Rep] Full Article | Graphical Abstract

STAT3 Expression by Myeloid Cells Is Detrimental for the T-Cell-Mediated Control of Infection with Mycobacterium tuberculosis

Scientists showed that M. tuberculosis-infected stat3^fl/fl lysm cre mice, defective for STAT3 in myeloid cells, contained lower bacterial load in lungs and spleens, reduced granuloma extension but higher levels of pulmonary neutrophils. [PLoS Pathog] Full Article

Differential Expression of CD8⁺ T Cell Cytotoxic Effector Molecules in Blood and Gastrointestinal Mucosa in HIV-1 Infection

Researchers elucidated the expression and coexpression patterns of granzyme (Gzm) A, B, and K in conjunction with perforin in rectosigmoid CD8⁺ T cells during HIV-1 infection. They found that expression of both perforin and GzmB, but not GzmA or GzmK, was reduced in mucosa compared with blood. [J Immunol] Abstract

IL-36/LXR Axis Modulates Cholesterol Metabolism and Immune Defense to Mycobacterium tuberculosis

To unveil the underlying mechanism of IL-36 induced antibacterial activity, scientists analyzed its role in the regulation of cholesterol metabolism, together with the involvement of liver X receptor (LXR) in this process. They report that, in Mycobacterium tuberculosis-infected macrophages, IL-36 signaling modulates cholesterol biosynthesis and efflux via LXR. [Sci Rep] Full Article

Inactivated Rotavirus Vaccine by Parenteral Administration Induces Mucosal Immunity in Mice

To improve the safety and efficacy of oral rotavirus vaccines, investigators developed an inactivated rotavirus vaccine (IRV) for parenteral administration. They demonstrated that IRV induced the expression of the gut homing receptor LPAM-1 on T and B cells in spleen and mLN of vaccinated mice. [Sci Rep] Full Article

Human Papilloma Virus-Specific T Cells Can Be Generated from Naïve T Cells for Use as an Immunotherapeutic Strategy for Immunocompromised Patients

Because Epstein-Barr Virus (EBV)-specific T cells have been highly successful in treating or preventing EBV-associated tumors, the authors hypothesized that the development of a manufacturing platform for human papilloma virus (HPV)-specific T cells from healthy donors could be used in a third-party setting to treat patients with high-risk/relapsed HPV-associated cancers. [Cytotherapy] Abstract

Impaired IFN-α-Mediated Signal in Dendritic Cells Differentiates Active from Latent Tuberculosis

Scientists performed a comparative evaluation of peripheral blood circulating dendritic cell (DC) subsets as well as of monocyte-derived interferon (IFN)-α DCs from patients with active tuberculosis (TB), subjects with latent tuberculosis infection (LTBI) and healthy donors (HDs). The proportion of circulating myeloid BDCA3⁺ DCs and plasmacytoid CD123⁺ DCs declined significantly in active TB patients compared to HDs, whereas the same subsets displayed a remarkable activation in LTBI subjects. [PLoS One] Full Article

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Skin Microbiota-Host Interactions

Researchers highlight how host-microbe interactions depend heavily on context, including the state of immune activation, host genetic predisposition, barrier status, microbe localization, and microbe-microbe interactions. [Nature] Abstract

Immune Response to Dengue and Zika

The authors discuss the following topics related to innate and adaptive immune responses to dengue virus and Zika virus: the interferon system as the key mechanism of host defense and viral target for immune evasion, antibody-mediated protection versus antibody-dependent enhancement, and T cell-mediated protection versus original T cell antigenic sin. [Annu Rev Immunol] Abstract

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Historic Deal Signed between Panacea Biotec and Serum Institute of India

Panacea Biotec Ltd. has signed two long-term collaboration agreements with Serum Institute of India Pvt. Ltd. (SII) and SII’s wholly owned subsidiary, Bilthovan Biologicals B.V.. [Panacea Biotec Limited] Press Release

World Health Organization Grants Prequalification to Bharat Biotech’s Rotavirus Vaccine, ROTAVAC^®

Bharat Biotech announced that the World Health Organization has awarded prequalification to the developing world’s first rotavirus vaccine, ROTAVAC^®. [Bharat Biotech] Press Release

The Wistar Institute Awarded More Than $1.4 Million to Create a Malaria Vaccine through Synthetic DNA-Based Technology

The Wistar Institute announced it has been awarded a $1,494,972 grant by the Bill & Melinda Gates Foundation to advance a DNA-based vaccine candidate for protection against malarial infection utilizing a synthetic DNA platform created in the lab of David B. Weiner, Ph.D., executive vice president, director of the Vaccine & Immunotherapy Center at The Wistar Institute and the W.W. Smith Charitable Trust Professor in Cancer Research. [The Wistar Institute] Press Release

GC Pharma Confirms Phase II/III Clinical Trial of New Protein Therapy for Hepatitis B

GC Pharma announced that it will proceed with a Phase II/III clinical trial for GC1102, the company’s investigational recombinant hepatitis B immune globulin for preventing the recurrence of hepatitis B virus infection following liver transplantation. [GC Pharma (PR Newswire Association LLC.)] Press Release

First Chronic Hepatitis B Patient Dosed in China in a Phase I Trial of T101 (Transgene’s TG1050 Technology)

Transgene announced that the first patient has been dosed in a Phase I clinical trial in China, evaluating T101, a therapeutic vaccine based on Transgene’s immunotherapy technology for the treatment of chronic hepatitis B virus infection. [Transgene SA] Press Release

U.S. Scientists Breathe a Sigh of Relief as Government Shutdown to End

It’s over—at least for the moment. The U.S. Senate voted 81–18 to advance legislation funding government activities, essentially ending a partial government shutdown that had moved into its third day. The House of Representatives is expected to follow suit, sending the bill to President Donald Trump for his signature. [ScienceInsider] Editorial

German Scientists Hope for Windfall from Incoming Government

Research budget could rise to 3.5% of gross domestic product if agreement struck during coalition talks holds. [Nature News] Editorial

Nobel Laureate Suggests He Could Fall on Sword over Colleague’s Bogus Paper

Shinya Yamanaka, who won a share of the 2012 Noble Prize in Physiology or Medicine for the discovery of induced pluripotent stem (iPS) cells, has suggested he could resign as director of Kyoto University’s Center for iPS Cell Research and Application in Japan over a fraudulent paper published by center researchers. [ScienceInsider] Editorial

NEW Aegean Conferences: 15^th International Conference on Innate Immunity
June 18-23, 2018
Crete, Greece

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NEW Assistant/Associate Professor – Microbiology and Immunology (SUNY Upstate Medical University)

Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

Scientist – Immunology (STEMCELL Technologies Inc.)

Postdoctoral Research Fellow – Malaria and Other Chronic Infectious Diseases (James Cook University)

Postdoctoral Research Scientist – Clinical Vaccine Development (University of Oxford)

Postdoctoral Scientist – Immunology (The Infectious Disease Research Institute)

Postdoctoral Scientist – HCV Vaccine Model Development (University of Oxford)

PhD Position – Immunology and Infectious Diseases (University of Freiburg)

Postdoctoral Fellow – Immunology/Infection Biology/Vaccinology (German Cancer Research Center)

Postdoctoral Fellows – Molecular Immunology and Infection Biology (CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences)

Postdoctoral Training Opportunity – Infection and Immunity (Institut Pasteur of Shanghai – Chinese Academy of Sciences)

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