Immunology of Infectious Disease News Volume 5.47 | Nov 29 2017

TOP STORY

Immune Evasion of Plasmodium falciparum by RIFIN via Inhibitory Receptors

The authors showed that P. falciparum uses immune inhibitory receptors to achieve immune evasion. They found that a subset of RIFINs binds to either leukocyte immunoglobulin-like receptor B1 or leukocyte-associated immunoglobulin-like receptor 1. [Nature] Abstract

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Natural Parasite Exposure Induces Protective Human Anti-Malarial Antibodies

Researchers cloned and characterized rare affinity-matured human NANP-reactive memory B cell antibodies elicited by natural Plasmodium falciparum exposure that potently inhibited parasite transmission and development in vivo. They unveiled the molecular details of antibody binding to two distinct protective epitopes within the NANP repeat. [Immunity] Abstract | Press Release | Graphical Abstract

The Pore-Forming Protein Gasdermin D Regulates Interleukin-1 Secretion from Living Macrophages

Investigators report that the pyroptosis regulator gasdermin D was necessary for IL-1β secretion from living macrophages that have been exposed to inflammasome activators, such as bacteria and their products or host-derived oxidized lipids. [Immunity] Abstract | Graphical Abstract

Initiation of HIV Neutralizing B Cell Lineages with Sequential Envelope Immunizations

Researchers report host tolerance mechanisms that limit the development of CD4-binding site (CD4bs), HCDR3-binder broadly neutralizing antibodies via sequential HIV-1 envelope (Env) vaccination. Vaccine-induced macaque CD4bs antibodies neutralized 7% of HIV-1 strains, recognized open Env trimers, and accumulated relatively modest somatic mutations. [Nat Commun] Full Article

Atypical Activation of Dendritic Cells by Plasmodium falciparum

The authors found that the activation of dendritic cells (DCs) by P. falciparum, the main causative agent of human malaria, induces a highly unusual phenotype by which DCs up-regulate costimulatory molecules and secretion of chemokines, but not of cytokines typical of inflammatory responses. [Proc Natl Acad Sci USA] Abstract

SNX8 Mediates IFNγ-Triggered Noncanonical Signaling Pathway and Host Defense against Listeria monocytogenes

Scientists identified sorting nexin 8 (SNX8) as an important component of the IFNγ-triggered noncanonical signaling pathway. SNX8-deficiency impaired IFNγ-triggered induction of a subset of downstream genes. Snx8^−/− mice infected with L. monocytogenes exhibited lower serum cytokine levels and higher bacterial loads in the livers and spleens, resulting in higher lethality. [Proc Natl Acad Sci USA] Abstract

Receptor Activator of NF-κB Orchestrates Activation of Antiviral Memory CD8 T Cells in the Spleen Marginal Zone

The authors describe a role for RANK in the coordinated function of antigen-presenting cells in the spleen marginal zone and triggering anti-viral immunity. Targeted deletion of RANK resulted in the selective loss of CD169⁺ marginal zone macrophages, which provided a niche for viral replication, while RANK signaling in dendritic cells promoted the recruitment and activation of anti-viral memory CD8 T cells. [Cell Rep] Full Article | Graphical Abstract

IL-15 Supports the Generation of Protective Lung-Resident Memory CD4 T Cells

Investigators identified two distinct pathways that lead to the generation of CD4 memory T cells (T_RM) in the lungs following influenza infection. The T_RM were transcriptionally distinct from conventional memory CD4 T cells and share a gene signature with CD8 T_RM. [Mucosal Immunol] Abstract

CD4⁺ T Cells Orchestrate Lethal Immune Pathology despite Fungal Clearance during Cryptococcus neoformans Meningoencephalitis

Scientists report a novel murine model of cryptococcal meningoencephalitis and a potential damaging role of T cells in disseminated cryptococcal central nervous system infection. In this model, fungal burdens plateaued in the infected brain by day 7 postinfection, but activation of microglia and accumulation of CD45^hi leukocytes was significantly delayed relative to fungal growth and did not peak until day 21. [MBio] Full Article

Vaccine-Elicited Memory CD4⁺ T Cell Expansion Is Impaired in the Lungs during Tuberculosis

To understand why protection is transient, researchers evaluated the ability of memory CD4⁺ T cells to expand, differentiate, and control Mycobacterium tuberculosis. Both naïve and memory CD4⁺ T cells initially proliferated exponentially, and the accumulation of memory T cells in the lung correlated with early bacterial control. [PLoS Pathog] Full Article

Systems Analysis of Latent HIV Reversal Reveals Altered Stress Kinase Signaling and Increased Cell Death in Infected T Cells

Scientists explored the acute signaling response of latent HIV-infected CD4⁺ T cells to identify dynamic phosphorylation signatures that could be targeted for therapy. Stimulation with CD3/CD28, PMA/ionomycin, or latency reversing agents prostratin and SAHA, yielded increased phosphorylation of IκBα, ERK, p38, and JNK in HIV-infected cells across two in vitro latency models. [Sci Rep] Full Article

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Impact of HIV-1 Envelope Conformation on ADCC Responses

The authors discuss envelope glycoprotein conformation affects antibody-dependent cellular cytotoxicity (ADCC) responses and in vitro measurements. [Trends Microbiol] Abstract

Mucocutaneous IL-17 Immunity in Mice and Humans: Host Defense vs. Excessive Inflammation

Scientists discuss the physiological and pathological roles of mouse and human IL-17A and IL-17F in host defense and excessive inflammation. [Mucosal Immunol] Abstract

The Crucial Roles of Th17-Related Cytokines/Signal Pathways in M. tuberculosis Infection

The authors discuss the need for future studies and the rationale for targeting T helper 17 (Th17)-related cytokines/signals as a potential adjunctive treatment. [Cell Mol Immunol] Abstract

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Soligenix Announces Presentation and Poster

Soligenix, Inc. announced that Dr. Oreola Donini, Chief Scientific Officer, presented preclinical data from two of its biodefense development programs. [Press release from Soligenix, Inc. discussing research presented at the 2017 Chemical and Biological Defense Science and Technology Conference, Long Beach] Press Release

Maxwell Biotech Venture Fund’s Portfolio Company Hepatera LLC Announces Positive Interim Results of Phase IIb Clinical Program of Myrcludex B

Hepatera LLC and its development partner MYR GmbH announced positive interim results in MYR 202 clinical trial, a Phase IIb study investigating Myrcudex B in chronic hepatitis delta infection. 120 subjects have been enrolled into this study in 15 centers in Russia and Germany and have completed active treatment phase. [Maxwell Biotech Venture Fund (PR Newswire Association LLC.)] Press Release

Takeda Initiates Phase I Clinical Trial of Zika Vaccine Candidate

Takeda Pharmaceutical Company Limited announced that its purified, inactivated, alum-adjuvanted, whole Zika virus vaccine candidate has progressed into a Phase I clinical trial, approximately 15 months after Takeda received a contract to develop a Zika vaccine from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority. [Takeda Pharmaceutical Company Limited] Press Release

Chembio Diagnostics Awarded UNICEF Contract to Supply Point-of-Care DPP^® Zika Assays and DPP^® Micro Readers

Chembio Diagnostics, Inc. announced that it has been awarded a conditional Long Term Arrangement from UNICEF for purchases of the company’s DPP^® Zika System, which is subject to Chembio satisfying certain conditions. [Chembio Diagnostics, Inc.] Press Release

Artemis Therapeutics Announces Issuance of European Patent for Artemisone for the Treatment of Viral Infections

Artemis Therapeutics, Inc. announced the recent issuance by the European Patent Office of European Patent No. 2839803 entitled “Methods and Compositions for Treating Viral Infections” covering the company’s lead product candidate, Artemisone, currently in development for the treatment of malaria and cytomegalovirus. [Artemis Therapeutics, Inc.] Press Release

AAAS and the University of Minnesota Announce 2017 Fellows

Haase has been named an American Association for the Advancement of Science (AAAS) Fellow for investigating HIV-1/AIDS and SIV lentivirus infections, especially for developing the SIV rhesus macaque model for vaccine development. Harris has been honored as an AAAS Fellow for his contributions to the understanding of mechanisms mutagenesis in evolution, in host-cell defense against viruses, and cancer development. [University of Minnesota] Press Release

Seven Faculty Are 2017 AAAS Fellows

Seven faculty members at Washington University in St. Louis are among 396 new fellows selected by the American Association for the Advancement of Science (AAAS), the world’s largest general scientific society. Caparon, professor of molecular microbiology in the Division of Biology & Biomedical Sciences, is being honored for his studies of disease-causing bacteria, such as those that cause strep throat, scarlet fever and urinary tract infections. [Washington University in St. Louis] Press Release

Microbe Scientists Launching Expanded Microbiome Center

Microbial science at Duke is taking a major step forward with the launch of the Duke Microbiome Center, which is intended to address growing scientific interest in the roles microbial communities play in human health, the environment and biotechnology. [Duke University] Press Release

The Medicines Company Announces Definitive Agreement to Sell Its Infectious Disease Business Unit to Melinta Therapeutics

The Medicines Company announced that it has entered into a definitive agreement to sell its infectious disease business unit to Melinta Therapeutics, Inc. [The Medicines Company] Press Release

Rise in Malaria Cases Sparks Fears of a Resurgence

Progress in the fight against a curable disease that kills hundreds of thousands of children has stalled, according to the World Health Organization. [Nature News] Editorial

Gene Therapy Hits a Peculiar Roadblock: A Virus Shortage

Eager to speed development of revolutionary treatments, the Food and Drug Administration recently announced that it would expedite approval of experimental gene therapies. But the regulatory process may not be the biggest obstacle. [The New York Times] Editorial

China to Roll Back Regulations for Traditional Medicine despite Safety Concerns

Support for traditional medicine in China goes right to the top. President Xi Jinping has called this type of medicine a “gem” of the country’s scientific heritage and promised to give alternative therapies and Western drugs equal government support. Now the country is taking dramatic steps to promote these cures even as researchers raise concerns about such treatments. [Nature News] Editorial

United States Bans Most Government Scientists from Travel to Cuba

The United States’s “new hostile policy towards Cuba undermines confidence” in joint research, says Luis Montero-Cabrera, a chemist at the University of Havana. The Trump administration, adds John Van Horn, a neuroscientist at the University of Southern California in Los Angeles, “has likely shut the door to many U.S.-Cuban interactions.” [ScienceInsider] Editorial

NEW Gordon Research Conferences: Biology of Acute Respiratory Infection
March 18-23, 2018
Ventura, California, United States

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NEW PhD Position – Human Influenza Vaccines (University of Bergen)

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