Immunology of Infectious Disease News Volume 8.05 | Feb 12 2020

TOP STORY

Febrile Temperature Critically Controls the Differentiation and Pathogenicity of T Helper 17 Cells

Investigators showed that febrile temperature selectively regulated T helper 17 (Th17) cell differentiation in vitro in enhancing IL-17, IL-17F, and IL-22 expression. Th17 cells generated under febrile temperature, compared with those under 37°C, showed enhanced pathogenic gene expression with increased pro-inflammatory activities in vivo. [Immunity] Abstract | Graphical Abstract

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BCL-2 Antagonism Sensitizes Cytotoxic T Cell-Resistant HIV Reservoirs to Elimination Ex Vivo

Researchers identified over-expression of the pro-survival factor BCL-2 as a distinguishing feature of CD4⁺ T-cells that survived cytotoxic T-cell killing. They showed that the inducible HIV reservoir was disproportionately present in BCL-2^hi subsets, in ex vivo CD4⁺ T-cells. [J Clin Invest] Abstract | Full Article

Influenza a Viruses Are Transmitted via the Air from the Nasal Respiratory Epithelium of Ferrets

Pairs of genetically tagged and untagged influenza A/H1N1, A/H3N2 and A/H5N1 viruses that are transmissible via the air were used to co-infect donor ferrets via the intranasal and intratracheal routes to cause an upper and lower respiratory tract infection, respectively. [Nat Commun] Full Article

Transcriptional Correlates of Tolerance and Lethality in Mice Predict Ebola Virus Disease Patient Outcomes

Scientists screened ten Collaborative Cross lines and identified clinical, virologic, and transcriptomic features that distinguished tolerant from lethal outcomes. Tolerance was associated with tightly regulated induction of immune and inflammatory responses shortly following infection, as well as reduced inflammatory macrophages and increased antigen-presenting cells, B-1 cells, and γδ T cells. [Cell Rep] Full Article | Graphical Abstract

TIGIT Is Upregulated by HIV-1 Infection and Marks a Highly Functional Adaptive and Mature Subset of Natural Killer Cells

Researchers performed a mass cytometry-based screen of NK cell receptor expression patterns in healthy controls and HIV⁺ individuals. They then focused mechanistic studies on the expression and function of T cell immunoreceptor with Ig and ITIM domains (TIGIT). [AIDS] Abstract

Deletion of Vaccinia Virus A40R Gene Improves the Immunogenicity of the HIV-1 Vaccine Candidate MVA-B

Investigators generated a novel recombinant virus, modified vaccinia virus Ankara (MVA) expressing HIV-1 gp120 and Gag-Pol-Nef of clade B (MVA-B) ΔA40R, by deleting in the MVA-B genome the vaccinia virus A40R gene, which encodes a protein with unknown immune function. The innate immune responses triggered by MVA-B ΔA40R in infected human macrophages, in comparison to parental MVA-B, revealed an increase in the mRNA expression levels of interferon (IFN)-β, IFN-induced genes, and chemokines. [Vaccines] Full Article | Download Full Article

17-β-Estradiol Increases Macrophage Activity through Activation of the GPER Estrogen Receptor and Improves the Response of Female Mice to Cryptococcus gattii

Scientists showed that female mice presented delayed mortality, increased neutrophil recruitment in bronchoalveolar lavage fluid and reduced fungal load after 24 hours of infection compared to male and ovariectomized female mice (OVX). 17β-estradiol replacement restored OVX female survival. [Cell Microbiol] Abstract

Alveolar Macrophage Chromatin Is Modified to Orchestrate Host Response to Mycobacterium bovis Infection

Scientists used chromatin immunoprecipitation sequencing, RNA-seq and miRNA-seq to examine the effect of M. bovis infection on the bovine alveolar macrophage (bAM) epigenome. They showed that H3K4me3 was more prevalent, at a genome-wide level, in chromatin from M. bovis-infected bAM compared to control non-infected bAM. [Front Genet] Full Article

Circulating Serum HBsAg Level Is a Biomarker for HBV-Specific T and B Cell Responses in Chronic Hepatitis B Patients

The authors compared the phenotypes and hepatitis B virus (HBV)-specific response of lymphocytes in chronic hepatitis B patients stratified by serum HBsAg levels <500 or >50,000IU/ml using immunological assays. HBs^hi patients had significantly higher expression of inhibitory PD-1 on CD4⁺ T cells, particularly among the TEMRA subset, and higher FcRL5 expression on B cells. [Sci Rep] Full Article

Identification of Plasmodium falciparum Circumsporozoite Protein-Specific CD8⁺ T Cell Epitopes in a Malaria Exposed Population

Cryopreserved PBMCs from nine HLA-typed subjects were stimulated with 23 8-10mer circumsporozoite protein peptides from the 3D7 parasite in IFN-ɣ ELISpot assays. The CD8⁺ T cell specificity of IFN-γ responses was confirmed in ELISpot assays using CD8⁺ T cell-enriched PBMC fractions after CD4⁺ cell depletion. [PLoS One] Full Article

Immunization with Full-Length Plasmodium falciparum Merozoite Surface Protein 1 Is Safe and Elicits Functional Cytophilic Antibodies in a Randomized First-in-Human Trial

Merozoite surface protein 1 (MSP1) was safe, well tolerated and immunogenic, with all vaccinees sero-converting independent of the dose. The MSP1-specific IgG and IgM titers persisted above levels found in malaria semi-immune humans for at least six months after the last immunization. [npj Vaccines] Full Article

Spaceflight and Simulated Microgravity Conditions Increase Virulence of Serratia Marcescens in the Drosophila melanogaster Infection Model

Researchers demonstrated that Serratia marcescens was significantly more lethal to Drosophila melanogaster after growth on the International Space Station than ground-based controls, but the increased virulence phenotype of S. marcescens did not persist after the bacterial cultures were passaged on the ground. [npj Microgravity] Full Article

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CD8⁺ T Cells in HIV Control, Cure and Prevention

Investigators discuss the increasing evidence derived from individuals who spontaneously control infection without antiretroviral therapy as well as pre-clinical immunization studies that provide a clear rationale for renewed efforts to develop a CD8⁺ T cell-based HIV vaccine in conjunction with B cell vaccine efforts. [Nat Rev Immunol] Abstract

From Ancient to Emerging Infections: The Odyssey of Viruses in the Male Genital Tract

The authors summarize the latest data regarding the sources of viruses in semen and the complex role of this body fluid in sexual transmission. Finally, they introduce key animal findings that are relevant for our understanding of viral infection and persistence in the human male genital tract and suggest future research directions. [Physiol Rev] Abstract

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Can-Fite Completes 50% Patient Enrollment in Phase III Rheumatoid Arthritis Study and Implements Interim Analysis

Can-Fite BioPharma Ltd. announced it has completed enrollment of approximately 50% of the 525 patients planned for its Phase III ACRobat™ trial to evaluate its drug candidate Piclidenoson as a first-line treatment for rheumatoid arthritis. [Can-Fite BioPharma, Ltd.] Press Release

SELLAS Announces Enrollment of First Patient in Phase I Trial of Galinpepimut-S (GPS) in Combination with Nivolumab (Opdivo^®) in Patients with Malignant Pleural Mesothelioma (MPM)

SELLAS Life Sciences Group, Inc. announced the enrollment of the first patient in an investigator-sponsored clinical trial of its Wilms tumor-1-targeting peptide immunotherapeutic agent, GPS, in combination with Bristol-Myers Squibb’s anti-PD-1 therapy, nivolumab, in patients with MPM. [SELLAS Life Sciences Group, Inc.] Press Release

Disease Caused by the Novel Coronavirus Officially Has a Name: Covid-19

Tedros Adhanom Ghebreyesus, the director-general of the World Health Organization, announced the name, giving a specific identifier to a disease that has been confirmed in more than 42,000 people and caused more than 1,000 deaths in China. [STAT News] Editorial

FDA Now Allows Certain Lab Animals to Be Retired and Adopted

The US Food and Drug Administration will now permit certain animals used in experiments to retire and be adopted rather than face euthanasia, according to internal documents reviewed by The Hill. Although the policy changed in November, there have not been any public statements from the agency. [The Scientist] Editorial

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March 1-5, 2020
Banff, Alberta, Canada

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NEW Postdoctoral Research – Cellular, Molecular, and Digital Medicine (Research Center for Molecular Medicine)

Scientist – Immunology (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Innate Immune Response to Mycobacterium tuberculosis (The Francis Crick Institute)

Postdoctoral Researcher – Pathogen/Host Cell Interactions (University Hospital of Müenster)

Postdoctoral Researcher – Microtubules in Viral Infection (Northwestern Feinberg School of Medicine)

Postdoctoral Fellow – HIV (Massachusetts General Hospital)

Postdoctoral Fellow – Vaccine Research (University of Rhode Island)

Postdoctoral Scientist – Tuberculosis Research (Texas Biomedical Research Institute)

Research Associate – Immunology (University Hospital of Muenster)

Postdoctoral Fellow – Immunology (Harvard T.H. Chan School of Public Health)

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