Volume 2.41 | Oct 22

Immunology of Infectious Disease News 2.41 October 22, 2014
Immunology of Infectious Disease News
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TRAIL+ NK Cells Control CD4+ T Cell Responses during Chronic Viral Infection to Limit Autoimmunity
Investigators found that natural killer (NK) cells specifically eliminated activated CD4+ T cells in the salivary gland during chronic murine cytomegalovirus infection. This was dependent on TNF-related apoptosis inducing ligand (TRAIL) expression by NK cells. [Immunity] Abstract | Graphical Abstract | Press Release
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PCSK9 Is a Critical Regulator of the Innate Immune Response and Septic Shock Outcome
The authors show that reduced proprotein convertase subtilisin/kexin type 9 (PCSK9) function is associated with increased pathogen lipid clearance via the low-density lipoprotein receptor, a decreased inflammatory response, and improved septic shock outcome. [Sci Transl Med] Abstract | Press Release

‘Division of Labor’ in Response to Host Oxidative Burst Drives a Fatal Cryptococcus gattii Outbreak
Investigators show that a subpopulation of intracellular C. gattii adopts a tubular mitochondrial morphology in response to host reactive oxygen species. These fungal cells then facilitate the rapid growth of neighboring C. gattii cells with non-tubular mitochondria, allowing for effective establishment of the pathogen within a macrophage intracellular niche. [Nat Commun] Full Article | Press Release

​Interleukin-1α Released from HSV-1-Infected Keratinocytes Acts as a Functional Alarmin in the Skin
The authors report that herpes simplex virus-1 (HSV-1)-infected keratinocytes actively release the also pro-inflammatory ​interleukin (IL)-1α, preserving the ability of infected cells to signal danger to the surrounding tissue. In vivo recruitment of leukocytes to early HSV-1 microinfection sites within the epidermis is dependent upon IL-1 signaling. [Nat Commun] Abstract

Role of Disease-Associated Tolerance in Infectious Superspreaders
Investigators show that superspreader hosts remain asymptomatic when they are treated with oral antibiotics. In contrast, nonsuperspreader Salmonella-infected hosts that are treated with oral antibiotics rapidly shed superspreader levels of the pathogen but display signs of morbidity. This morbidity is linked to an increase in inflammatory myeloid cells in the spleen followed by increased production of acute-phase proteins and proinflammatory cytokines. [Proc Natl Acad Sci USA] Abstract | Press Release

Female Resistance to Pneumonia Identifies Lung Macrophage Nitric Oxide Synthase-3 as a Therapeutic Target
To identify new approaches to enhance innate immunity to bacterial pneumonia, scientists investigated the natural experiment of gender differences in resistance to infections. In vitro, lung macrophages from female mice and humans show better killing of ingested bacteria. [eLife] Abstract | Full Article | Editorial

Protection and Mechanism of Action of a Novel Human Respiratory Syncytial Virus Vaccine Candidate Based on the Extracellular Domain of Small Hydrophobic Protein
Scientists demonstrate that a vaccine based on the extracellular domain (SHe) of the small hydrophobic (SH) protein of human respiratory syncytial virus, reduced viral replication in challenged laboratory mice and in cotton rats. Using a conditional cell depletion method, they provide evidence that alveolar macrophages are involved in the protection by SHe-specific antibodies. [EMBO Mol Med] Full Article | Press Release


Slaying the Trojan Horse: Natural Killer Cells Exhibit Robust Anti-HIV-1 Antibody-Dependent Activation and Cytolysis against Allogeneic T-Cells
As HIV-1 vaccines need to elicit immune responses capable of controlling both free and cell-associated virus, researchers evaluated the potential of natural killer cells to respond in an antibody-dependent manner to allogeneic T-cells bearing HIV-1 antigens. [J Virol] Abstract

Contact-Induced Mitochondria Polarization Supports HIV-1 Virological Synapse Formation
Investigators report that contact between an HIV-1 infected T cell and an uninfected target T cell specifically triggers polarization of mitochondria concomitant with recruitment of the major HIV-1 structural protein Gag to the site of cell-cell contact. [J Virol] Abstract | Full Article

Shorter Telomere Length Predicts Poorer Immunological Recovery in Virologically Suppressed HIV-1 Infected Patients Treated with Combined Antiretroviral Therapy
Because telomere dysregulation can lead to an abnormal cell proliferation, researchers hypothesized that lack of CD4 recovery may be related to telomere defects so they evaluated the association between telomere length and CD4+ T-cell recovery 48 weeks aftercombined antiretroviral therapy initiation in virologically suppressed patients, and its possible relation with the oxidative and nitrosative stress markers. [J Acquir Immune Defic Syndr] Abstract

Suppression of Foxo1 Activity and Down-Modulation of CD62L (L-Selectin) in HIV-1 Infected Resting CD4 T Cells
Investigators report that HIV-1 down-modulates CD62L in productively infected naïve and memory resting CD4 T cells while suppressing Foxo1 activity and the expression of KLF2 mRNA. Partial T cell activation was further evident as an increase in CD69 expression. [PLoS One] Full Article

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Innate Sensing of Malaria Parasites
The authors highlight the cellular and molecular mechanisms by which Plasmodium infection is sensed by different families of innate immune receptors. They also discuss how these events mediate both host resistance to infection and the pathogenesis of malaria. [Nat Rev Immunol] Abstract

Eradicating HIV-1 Infection: Seeking to Clear a Persistent Pathogen
Recent studies have focused on the development of therapies to disrupt latency. The authors explore new approaches to eradicate established HIV-1 infection and avoid the burden of lifelong antiretroviral therapy. [Nat Rev Microbiol] Abstract

Autophagy and Burkholderia
Some bacteria are seemingly able to evade autophagy and Burkholderia pseudomallei is one of them. The authors discuss the autophagic processes that may be activated by host cells to provide protection against infection by this bacterial pathogen. [Immunol Cell Biol] Abstract

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Chimerix’s Brincidofovir Shows Potential Survival Benefit in Adenovirus Infection
Chimerix, Inc. announced preliminary data for its investigational antiviral brincidofovir (BCV, CMX001) showing improved survival for patients with adenovirus in the open-label pilot portion of the Phase III AdVise Trial. [Press release from Chimerix, Inc. discussing research presented at IDWeek 2014™, Philadelphia] Press Release

NanoBio to Present Data Demonstrating the Potential for its Intranasal Vaccine to Protect against Genital Herpes Infection
The company highlighted the advantages of its nanoemulsion adjuvant in the development of a prophylactic genital herpes vaccine that induces protection by eliciting both systemic and mucosal immune responses. [Press release from NanoBio Corporation discussing research presented at the Keystone Symposia Conference, The Modes of Action of Vaccine Adjuvants (S1), Seattle] Press Release

Theralase Presents Latest Research on Destruction of Cancer and Bacteria
Theralase Technologies Inc. announced that it has presented its latest research on the success of its photodynamic compounds in the destruction of cancer and bacteria. [Press release from Theralase Technologies Inc. (TheNewswire) discussing research presented at the 10th International Symposium on Photodynamic Therapy and Photodiagnosis in Clinical Practice, Brixen] Press Release | Poster

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Sanofi Pasteur and Immune Design Enter Broad Collaboration for the Development of a Herpes Simplex Virus Therapy
Immune Design Corp. announced that it has entered into a broad collaboration for the development of a herpes simplex virus immune therapy with Sanofi Pasteur. [Immune Design Corp.] Press Release

OHSU, Partners Kineta, U of Washington, VGTI Florida Awarded $10 Million NIH Contract to Develop New Vaccine Adjuvants
Oregon Health & Science University’s Vaccine & Gene Therapy Institute (OHSU) has been awarded a $10 million contract from the National Institute of Allergy and Infectious Diseases. Kineta, Inc., the University of Washington Center for Innate Immunity and Immune Disease, and the Vaccine & Gene Therapy Institute of Florida (VGTI Florida) will collaborate with OHSU as major sub-contractors to develop new vaccine adjuvants that could boost the effectiveness of a wide range of human vaccines for infectious diseases including West Nile virus, dengue and Japanese encephalitis. [Oregon Health & Science University] Press Release

Scripps Research Institute Team Receives $6.6 Million to Investigate Deadly Lassa Virus
Scientists from The Scripps Research Institute have been awarded $6.6 million from the National Institutes of Health to lead an investigation of Lassa fever virus, the most prevalent virus-induced hemorrhagic fever disease in Africa. [The Scripps Research Institute] Press Release

NYU Langone Medical Center to Spearhead Multi-Institutional MRSA Research Funded by the National Institutes of Health
Researchers at NYU Langone Medical Center will lead a consortium of five institutions on a $6.5 million contract from the National Institutes of Health directed at discovery of the fundamental immunology, microbial genetics, protein structure and proteomics of Staphylococcus aureus. [NYU Langone Medical Center] Press Release

Imaging Center to Unravel Secrets of Immune System
University of Queensland researchers will play a key role in a new $39 million research center working to unravel the secrets of the immune system. The program will deliver new insights into the molecules and cellular mechanisms involved in diseases such as cancer, infectious diseases and autoimmune diseases. [The University of Queensland] Press Release

US FDA Accepts for Review a Biologics License Application for Merck and Sanofi Pasteur’s Investigational Pediatric Hexavalent Vaccine
Merck and Sanofi Pasteur announced that the Biologics License Application filed for the companies’ investigational pediatric hexavalent vaccine has been accepted for review by the U.S. Food and Drug Administration (FDA). If approved, it would be the first pediatric combination vaccine in the United States designed to help protect against six important diseases – diphtheria, tetanus, pertussis, polio, invasive disease caused by Haemophilus influenzae type b, and hepatitis B. [Merck & Co., Inc.] Press Release

Imaxio Signs an Option for a License Agreement with the German Cancer Research Center (DKFZ)
Imaxio announced that it has signed an option for a license agreement with the world-renowned DKFZ. The DKFZ is to make an internal evaluation of Imaxio’s IMX313 pro-immunogenic technology. It will be tested to enhance the efficacy of one of the center’s candidate vaccines, which is indicated in the prevention of human papillomavirus infections. [Imaxio] Press Release

NIH Grants License Agreement for Candidate Ebola Vaccines
The National Institute of Allergy and Infectious Diseases announced a new license agreement aimed at advancing dual-purpose candidate vaccines to protect against rabies and Ebola viruses. [National Institute of Allergy and Infectious Diseases] Press Release
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NEW Cell Symposia: The Multifaceted Roles of Type 2 Immunity
December 10-12, 2014
Bruges, Belgium

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NEW Associate Professor – Molecular Immunology (Chiba University)

Professorship Position – Virology (Medical University of Vienna)

PhD Position – Childhood Respiratory Virus Infections and Development of Asthma (Norwegian University of Science and Technology)

Research Fellow – Gene Expression of Immune Cells in Response to Infection (The University of Nottingham)

PhD Position – Innate Immunity / Microscopy (University Duisburg-Essen)

Postdoctoral Fellowship – Parasitology (Institut Pasteur)

Postdoctoral Fellow – Immunology of Human Enteric Infections (University of Utah)

PhD Studentship – Immune Activation in Human Retroviral Pathologies (KU Leuven)

Scientist – Recombinant Molecules and Antibodies (STEMCELL Technologies Inc.)

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