Immunology of Infectious Disease News Volume 6.01 | Jan 10 2018

TOP STORY

S1P-Dependent Interorgan Trafficking of Group 2 Innate Lymphoid Cells Supports Host Defense

Innate lymphoid cells (ILCs) are innate counterparts of adaptive T lymphocytes, contributing to host defense, tissue repair, metabolic homeostasis, and inflammatory diseases. Investigators showed that interleukin-25- or helminth-induced inflammatory ILC2s are circulating cells that arise from resting ILC2s residing in intestinal lamina propria. [Science] Abstract

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Local Proliferation Maintains a Stable Pool of Tissue-Resident Memory T Cells after Antiviral Recall Responses

Researchers found that skin tissue-resident memory T cells (T_RM cells) engaged virus-infected cells, proliferated in situ in response to local antigen encounter and did not migrate out of the epidermis, where they exclusively reside. As a consequence, secondary T_RM cells formed from pre-existing T_RM cells, as well as from precursors recruited from the circulation. [Nat Immunol] Abstract

BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity

In a randomized placebo-controlled human challenge study, scientists found that bacillus Calmette-Guérin (BCG) vaccination induced genome-wide epigenetic reprogramming of monocytes and protected against experimental infection with an attenuated yellow fever virus vaccine strain. Epigenetic reprogramming was accompanied by functional changes indicative of trained immunity. [Cell Host Microbe] Abstract | Graphical Abstract

Hepatitis B Virus-Specific T Cells Associate with Viral Control upon Nucleos(t)ide-Analogue Therapy Discontinuation

The authors identified the presence of functional hepatitis B virus (HBV)-specific T cells as a candidate immunological biomarker for safe therapy discontinuation in chronic HBV patients. Furthermore, the persistent and functional antiviral activity of PD-1⁺ HBV-specific T cells highlights the potential beneficial role of the expression of T cell exhaustion markers during human chronic viral infection. [J Clin Invest] Full Article

Influenza-Specific Lung-Resident Memory T Cells Are Proliferative and Polyfunctional and Maintain Diverse TCR Profiles

Scientists showed that human lung contains a population of CD8⁺ resident memory T (Trm) cells that are highly proliferative and have polyfunctional progeny. They observed that different influenza virus-specific CD8⁺ T cell specificities differentiated into Trm cells with varying efficiencies and that the size of the influenza-specific CD8⁺ T cell population persisting in the lung directly correlated with the efficiency of differentiation into Trm cells. [J Clin Invest] Full Article

Zika Virus Infection Induces Host Inflammatory Responses by Facilitating NLRP3 Inflammasome Assembly and Interleukin-1β Secretion

Investigators report that Zika virus (ZIKV) stimulates IL-1β secretion in infected patients, human peripheral blood mononuclear cells and macrophages, mice, and mice bone marrow dendritic cells. The knockdown of NLRP3 in cells and knockout of NLRP3 in mice inhibit ZIKV-mediated IL-1β secretion, indicating an essential role for NLRP3 in ZIKV-induced IL-1β activation. [Nat Commun] Full Article

Human Cytomegalovirus-Encoded US9 Targets MAVS and STING Signaling to Evade Type I Interferon Immune Responses

The authors showed that human cytomegalovirus glycoprotein US9 inhibits the type I interferon-β response by targeting the mitochondrial antiviral-signaling protein (MAVS) and stimulator of interferon genes (STING)-mediated signaling pathways. US9 accumulation in mitochondria attenuated the mitochondrial membrane potential, leading to promotion of MAVS leakage from the mitochondria. [Nat Commun] Full Article

Signaling by the Epstein-Barr Virus LMP1 Protein Induces Potent Cytotoxic CD4⁺ and CD8⁺ T Cell Responses

Researchers showed that LMP1 expression in B cells induces potent cytotoxic CD4 and CD8 T cell responses, by enhancing antigen presentation and costimulation by CD70, OX40 ligand, and 4-1BB ligand. Their data further suggested that cytotoxic CD4 cells hold superior therapeutic value for LMP1-driven lymphomas. [Proc Natl Acad Sci USA] Abstract

Infection and Depletion of CD4⁺ Group-1 Innate Lymphoid Cells by HIV-1 via Type-I Interferon Pathway

Scientists report that human group-1 innate lymphoid cells (ILC1s) comprising of CD4⁺ and CD4^– subpopulations were present in various human lymphoid organs, but with different transcription programs and functions. Importantly, CD4⁺ ILC1s expressed HIV-1 co-receptors and were productively infected by HIV-1 in vitro and in vivo. [PLoS Pathog] Full Article

Mycobacterium tuberculosis-Induced miR-155 Subverts Autophagy by Targeting ATG3 in Human Dendritic Cells

Given the crucial role of human primary dendritic cells (DC) in host immunity control, researchers characterized Mycobacterium tuberculosis-DC interplay by studying the contribution of cellular miRNAs in the post-transcriptional regulation of autophagy related genes. Gene ontology analysis showed that miR-155, miR-155* and miR-146a target mRNAs with a significant enrichment in biological processes linked to autophagy. [PLoS Pathog] Full Article

Type I Interferons Instigate Fetal Demise after Zika Virus Infection

Type I interferons (IFNs) are essential for host resistance against Zika virus (ZIKV), and IFN-α/β receptor (IFNAR)–deficient mice are highly susceptible to ZIKV infection. Investigators challenged Ifnar1^−/− dams mated with Ifnar1^+/− sires with ZIKV. Yet, rather unexpectedly, they found that only Ifnar1^+/− fetuses were resorbed after ZIKV infection during early pregnancy, whereas their Ifnar1^−/− littermates continue to develop. [Sci Immunol] Abstract | Press Release

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The Role of Vaccines in Preventing Bacterial Antimicrobial Resistance

The authors highlight the value of vaccines as an additional modality to combat antimicrobial resistance globally, using select examples. They provide perspectives on how vaccines could be more effectively used in this effort. [Nat Med] Abstract

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Ascentage Pharma Announces Acceptance of IND Application by China FDA for Clinical Study of Novel IAP Inhibitor to Treat Hepatitis B Infection

Ascentage Pharma announced that the China Food and Drug Administration (FDA) has accepted the Investigational New Drug (IND) application for APG-1387, a novel small molecule inhibitors of apoptosis (IAP) inhibitor for the treatment of the hepatitis B virus infection. [Ascentage Pharma] Press Release

BiondVax Universal Flu Vaccine Patent Granted in India

BiondVax Pharmaceuticals Ltd., developer of M-001, the Universal Flu Vaccine candidate currently in preparation for a Phase III clinical trial, announced that one of its key patents titled “A Synthetic or Recombinant Influenza Multi-Epitope Polypeptide” has been granted in India. [BiondVax Pharmaceuticals Ltd.] Press Release

FDA Accepts New Drug Applications for Merck’s Doravirine, the Company’s Investigational Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI), for Treatment of HIV-1 Infection

Merck announced that the FDA has accepted for review two New Drug Applications for doravirine, the company’s investigational NNRTI for the treatment of HIV-1 infection in adults. [Merck & Co., Inc.] Press Release

Sabin to Tackle Pandemic Flu

The Sabin Vaccine Institute announced a new three-year $6.6 million grant to help speed the development of next generation influenza vaccines and support related immunization issues. [The Sabin Vaccine Institute] Press Release

Rising Star Appointed UK Science Minister

The United Kingdom has gained a new science minister as part of a broader reshuffle of government posts. Sam Gyimah, who moves from the Ministry of Justice, was appointed minister for universities and science, replacing Jo Johnson. [Nature News] Editorial

Faced with Public Pressure, Research Institutions Step Up Reporting of Clinical Trial Results

The reporting of clinical trial results to a public database — mandated by a ten-year-old federal law — has improved sharply in the last two years, with universities and other nonprofit research centers leading the way. [STAT News] Editorial

NEW Gordon Research Conferences: Cellular and Molecular Fungal Biology
June 17-22, 2018
Holderness, New Hampshire, United States

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NEW Research Technologist – Cell Separation (STEMCELL Technologies Inc.)

NEW Postdoctoral Position – Antibody Directed Vaccinology/Molecular Biology (University of Copenhagen)

NEW Postdoctoral Scientist – Immunology (The Infectious Disease Research Institute)

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

Scientist – Immunology (STEMCELL Technologies Inc.)

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

University Lecturer – Infection Biology (Umeå University)

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)

Group Leader – Infection, Immunity and Tumour Immunology (University of Oxford)

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

Postdoctoral Scientist – Innate Immunity/Host-Pathogen Interactions (Rutgers New Jersey Medical School)

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