Immunology of Infectious Disease News Volume 1.39 | Dec 11 2013

Dissociation of Innate Immune Responses in Microglia Infected with Listeria monocytogenes
Investigators present evidence that microglia control Listeria infection differently than macrophages. Infection of primary microglial cultures and murine cell lines with Listeria resulted in a dual function of the two gene expression programmes involved in early and late immune responses in macrophages. [Glia] Abstract

MyD88 Signaling is Directly Involved in the Development of Murine Placental Malaria
Scientists utilized a mouse model of placental malaria infection to determine the importance of MyD88 in the host immune response to Plasmodium during pregnancy. [Infect Immun] Abstract

Liver Accumulation of Plasmodium chabaudi-Infected Red Blood Cells and Modulation of Regulatory T Cell and Dendritic Cell Responses
It is postulated that accumulation of malaria-infected red blood cells in the liver could be a parasitic escape mechanism against full destruction by the host immune system. Therefore, researchers evaluated the in vivo mechanism of this accumulation and its potential immunological consequences. [PLoS One] Full Article

PD-1 Dependent Exhaustion of CD8⁺ T Cells Drives Chronic Malaria
Scientists used an experimental rodent malaria model to show that PD-1 mediates up to a 95% reduction in numbers and functional capacity of parasite-specific CD8⁺ T cells. Furthermore, in contrast to widely held views, parasite-specific CD8⁺ T cells are required to control both acute and chronic blood-stage disease even when parasite-specific antibodies and CD4⁺ T cells are present. [Cell Rep] Full Article | Graphical Abstract

HIV

Expression of Chimeric Receptor CD4ζ by Natural Killer Cells Derived from Human Pluripotent Stem Cells Improves In Vitro Activity but Does Not Enhance Suppression of HIV Infection In Vivo
Researchers hypothesized that expression of this CD4ζ receptor would more efficiently direct human embryonic stem cell (hESC)- and induced pluripotent stem cell (iPSC)-derived natural killer (NK) cells to target HIV-infected cells. In vitro studies showed the CD4ζ expressing hESC- and iPSC-NK cells inhibited HIV replication in CD4+ T cells more efficiently than their unmodified counterparts. [Stem Cells] Abstract

Vaccine-Elicited Human T Cells Recognizing Conserved Protein Regions Inhibit HIV-1
The authors describe the first-ever administration of conserved immunogen vaccines vectored using prime-boost regimens of DNA, simian adenovirus and modified vaccinia virus Ankara to uninfected UK volunteers. The vaccine induced high levels of effector T cells that recognized virus-infected autologous CD4⁺ cells and inhibited HIV-1 replication by up to 5.79 log₁₀. [Mol Ther] Abstract

Anti-HIV Antibody-Dependent Activation of NK Cells Impairs NKp46 Expression
Scientists found that activation of NK cells by anti-HIV or anti-CD16 antibodies (Abs) resulted in NKp46 downregulation. The addition of a matrix metalloproteinase inhibitor attenuated NKp46 downregulation following NK cell activation by anti-HIV Abs. [J Immunol] Abstract

High Multiplicity HIV-1 Infection and Neutralizing Antibody Evasion Mediated by the Macrophage-T Cell Virological Synapse
Using a primary cell-based co-culture model, researchers showed that monocyte-derived macrophages efficiently transmit a high multiplicity HIV-1 infection to autologous CD4⁺ T cells through a viral envelope glycoprotein-receptor and actin-dependent virological synapse, facilitated by interactions between ICAM-1 and LFA-1. [J Virol] Abstract

Adaptation of CD8 T Cell Responses to Changing HIV-1 Sequences in a Cohort of HIV-1 Infected Individuals Not Selected for a Certain HLA Allele
Investigators studied 19 antiretroviral-naïve HIV-1 infected individuals with different disease courses longitudinally. A median number of 12 (range 2-24) CD8 T cell responses towards Gag and Nef were detected per study subject. A total of 30 declining CD8 T cell responses were studied in detail and viral sequence analyses showed amino acid changes in 25 of these. [PLoS One] Full Article

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Medimmune and The Johns Hopkins University Announce Five-Year, $6.5 Million Collaboration to Drive Medical Research and Discovery
MedImmune, AstraZeneca’s global biologics research and development arm, and The Johns Hopkins University announced they have entered into a five-year, $6.5 million research collaboration. The joint research projects will focus on MedImmune’s therapeutic areas of interest, including cardiovascular and metabolic disease; oncology; respiratory, inflammation and autoimmunity; infectious disease and neuroscience. [MedImmune, LLC] Press Release

FDA Grants Astellas Qualified Infectious Disease Product Designation for Isavuconazole for the Treatment of Invasive Aspergillosis
Astellas Pharma US, Inc. announced that the U.S. Food and Drug Administration (FDA) designated isavuconazole as a Qualified Infectious Disease Product (QIDP) for the treatment of invasive aspergillosis. QIDP status provides priority review and a five-year extension of market exclusivity if a product receiving such a designation is approved in the United States. [Astellas Pharma US, Inc.] Press Release

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

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NEW Postdoctoral Associate – Molecular Biology (State University of New York)

Postdoctoral Position – Immunology (The Wistar Institute)

Research Scientist – Veterinary Immunology (Institute of Virology and Immunology)

Postdoctoral Fellowship – Anti-Viral Property of IL-27 and Related Proteins in Innate Immune Responses to HIV and Other Virus Infections (Leidos Biomedical Research, Inc.)

Postdoctoral Position – Pathogenesis of Enterovirus 71 (Institut Pasteur)

Postdoctoral Position – Importance of Trypanosome Motility during the Early Infection in the Mammalian Host (Institut Pasteur)

PhD Studentship – Systems Biology (University of Oxford)

Research Technologist – Human Pluripotent Stem Cell Products (STEMCELL Technologies Inc.)

Research Associate/Scientist – Antibodies Group (STEMCELL Technologies Inc.)

Scientist – Particle Chemistry (STEMCELL Technologies Inc.)

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