Immunology of Infectious Disease News Volume 7.46 | Nov 27 2019

TOP STORY

Host Resistance Factor SLC11A1 Restricts Salmonella Growth Through Magnesium Deprivation

The authors compared Salmonella infection of coisogenic mice with different SLC11A1 alleles. SLC11A1 reduced Salmonella replication and triggered up-regulation of uptake systems for divalent metal cations but no other stress responses. [Science] Abstract

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Principles Governing Establishment Versus Collapse of HIV-1 Cellular Spread

Following ex vivo activation of latently infected CD4 T cells without de novo infection, stochastic cell division and death contributed to high variability in the magnitude of initial virus release. Transition to exponential HIV-1 spread often failed due to release of an insufficient amount of replication-competent virus. [Cell Host Microbe] Abstract

Leishmania RNA Virus Exacerbates Leishmaniasis by Subverting Innate Immunity via TLR3-Mediated NLRP3 Inflammasome Inhibition

Investigators combined human and mouse data to demonstrate that Leishmania RNA virus triggered TLR3 and TRIF to induce type I IFN production, which induced autophagy. This process resulted in ATG5-mediated degradation of NLRP3 and ASC, thereby limiting NLRP3 inflammasome activation in macrophages. [Nat Commun] Full Article

An MPER Antibody Neutralizes HIV-1 Using Germline Features Shared Among Donors

Researchers describe an membrane-proximal external region (MPER) broadly neutralizing antibody from the major IgG1 subclass, PGZL1, which shared germline V/D-region genes with 4E10, had a shorter CDRH3, and iwasless polyreactive. A recombinant sublineage variant pan-neutralized a 130-isolate panel at 1.4μg/ml [Nat Commun] Full Article

IL-12 Blocks Tfh Cell Differentiation During Salmonella Infection, Thereby Contributing to Germinal Center Suppression

Scientists identified that IL-12, but not interferon-γ, directly suppressed T follicular helper (Tfh) cell differentiation of T cells intrinsically. Administering recombinant IL-12 during nitropheny-chicken gamma Globulin immunization also suppressed Tfh cell differentiation and germinal centers B cells, indicating that IL-12 was sufficient to suppress Tfh cell differentiation independent of Salmonella enterica serovar Typhimurium infection. [Cell Rep] Full Article | Graphical Abstract

Flt3L-Mediated Expansion of Plasmacytoid Dendritic Cells Suppresses HIV Infection in Humanized Mice

HIV infection of humanized mice induced systemic depletion of plasmacytoid dendritic cells (pDC), and in the presence of soluble FMS-like tyrosine kinase 3 ligand (Flt3L), pDC levels remained elevated. Flt3L significantly delayed the onset of viremia and reduced viral replication via a process that was dependent on pDC and mediated through an enhanced early IFN-I response. [Cell Rep] Full Article | Graphical Abstract | Press Release

MicroRNA-33/33^* Inhibit the Activation of MAVS Through AMPK in Antiviral Innate Immunity

Scientists report that VSV stimulation decreased the expression of miR-33/33^* through an IFNAR-dependent manner in macrophages. Overexpression of miR-33/33^* resulted in impaired RIG-I signaling, enhancing viral load and lethality whereas attenuating type I interferon production both in vitro and in vivo. [Cell Mol Immunol] Abstract

Entamoeba histolytica Stimulates the Alarmin Molecule HMGB1 from Macrophages to Amplify Innate Host Defenses

The authors investigated the induction and release of the endogenous alarmin molecule high-mobility group box 1 (HMGB1) that acted as a pro-inflammatory cytokine and chemoattractant during Entamoeba histolytica (Eh) infection. Eh in contact with macrophage induced a dose- and time-dependent secretion of HMGB1 in the absence of cell death. [Mucosal Immunol] Abstract

G-CSFR Antagonism Reduces Neutrophilic Inflammation During Pneumococcal and Influenza Respiratory Infections without Compromising Clearance

Neutrophil trafficking was targeted with a granulocyte-colony stimulating factor receptor monoclonal antibody during Streptococcus pneumoniae or influenza A virus lung infection in mice. Researchers demonstrated that neutrophils were indispensable for the clearance of S. pneumoniae from the airways using an anti-Ly6G monoclonal antibody, as the complete inhibition of neutrophil recruitment markedly compromised bacterial clearance. [Sci Rep] Full Article

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Adolescent Tuberculosis

The authors discuss up-to-date information about tuberculosis in adolescence, with a focus on the management of infection and disease, including HIV co-infection and rifampicin-resistant tuberculosis. They outline the progress in vaccine development and highlight important directions for future research. [Lancet Child Adolesc Health] Abstract

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TFF Pharmaceuticals Announces Initiation of Phase I Clinical Trial of Voriconazole Inhalation Powder, to Treat Invasive Pulmonary Aspergillosis (IPA)

TFF Pharmaceuticals, Inc. announced the initiation of its Phase I clinical trial of voriconazole inhalation powder, a next-generation, direct-to-lung, inhaled dry powder version of Voriconazole, generally considered to be the most effective antifungal drug for treating IPA. [FF Pharmaceuticals, Inc.] Press Release

Prokarium Announces MHRA Acceptance to Run Phase I Trial of Lead Vaccine Against Enteric Fever

Prokarium has received Clinical Trial Authorizatio acceptance from the UK Medicines and Healthcare products Regulatory Agency (MHRA) to run a first-in-human Phase I trial with Entervax™, a bivalent vaccine against enteric fever. [Prokarium (BusinessWire, Inc.)] Press Release

Ebola Response on Lockdown as Violence Flares

A surge in violence and unrest has forced Ebola responders in the city of Beni in the eastern Democratic Republic of the Congo to remain indoors for the past week – hampering efforts to contain the virus. WHO has temporarily evacuated one-third of its 120 staff members stationed in the city. [Nature News] Editorial

Polio Vaccination Causes More Infections Than Wild Virus

Nigeria, Democratic Republic of Congo, Central African Republic, and Angola have experienced nine new cases of polio caused by the live virus in oral polio vaccines that has mutated into an infectious form, according to statistics released November 20 by the WHO. That brings the global total of these types of infections to 157 for the year, and it means that more children are paralyzed as a result of such vaccine-derived infections than illnesses caused by the wildtype virus. [The Scientist] Editorial

Dengue Cases Drop After Bacteria-Infected Mosquitoes Released

Mosquitoes infected with Wolbachia bacteria and released into the wild are associated with a sharp decrease in dengue fever infections in humans, scientists reported November 21 at the American Society of Tropical Medicine and Hygiene’s annual meeting. [The Scientist] Editorial

NEW Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies
January 9-12, 2020
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NEW Senior Lectuerer – Infectious Disease and Microbiomes (University of Liverpool)

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Postdoctoral Fellow – Cerebral Malaria (European Molecular Biology Laboratory)

Postdoctoral Positions – HIV (University of New South Wales)

Faculty Position – Infectious Disease Research (Tsinghua University School of Medicine)

Postdoctoral Associates – Virology and Vaccine Development (University of Minnesota)

Scientist – Infectious Disease (Infectious Disease Research Institute)

Postdoctoral Position – HIV (Tulane University)

Postdoctoral Position/PhD Student – Infectious Diseases, Host-Pathogen Interactions and Immunology (Purdue University)

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