Immunology of Infectious Disease News Volume 3.19 | May 20 2015

IL-10-Producing Intestinal Macrophages Prevent Excessive Antibacterial Innate Immunity by Limiting IL-23 Synthesis
Investigators showed that a subset of mouse colonic macrophages constitutively produce the anti-inflammatory cytokine IL-10. In mice infected with Citrobacter rodentium, a model for enteropathogenic Escherichia coli infection in humans, these macrophages are required to prevent intestinal pathology. [Nat Commun] Abstract

Helminth Infection and Commensal Microbiota Drive Early IL-10 Production in the Skin by CD4⁺ T Cells that Are Functionally Suppressive
Using a murine model of repeated infection with Schistosoma mansoni larvae, researchers showed that the skin infection site becomes rich in regulatory IL-10, whilst in its absence, inflammation, neutrophil recruitment, and local lymphocyte proliferation is increased. [PLoS Pathog] Full Article

Strain- and Host Species-Specific Inflammasome Activation, IL-1β Release, and Cell Death in Macrophages Infected with Uropathogenic Escherichia coli
Researchers showed that uropathogenic E. coli strains CFT073 and UTI89 trigger inflammasome activation and lytic cell death in human macrophages. In mouse macrophages, UTI89 triggered cell death only at a high multiplicity of infection, and CFT073-mediated inflammasome responses were completely NLRP3-dependent. [Mucosal Immunol] Abstract

DDX60 Is Involved in RIG-I-Dependent and Independent Antiviral Responses, and Its Function Is Attenuated by Virus-Induced EGFR Activation
The authors report that DDX60 is a sentinel for both RIG-I activation and viral RNA degradation. They showed that DDX60 is an upstream factor of RIG-I that activates RIG-I signaling in a ligand-specific manner. [Cell Rep] Full Article | Graphical Abstract

Mucosal Delivery of a Vectored RSV Vaccine Is Safe and Elicits Protective Immunity in Rodents and Nonhuman Primates
Investigators generated a new genetic vaccine based on chimpanzee adenovirus (PanAd3-RSV) and modified vaccinia ankara respiratory syncytial virus (MVA-RSV) encoding the F, N, and M2-1 proteins of RSV, for the induction of neutralizing antibodies and broad cellular immunity. Heterologous prime boost with PanAd3-RSV and MVA-RSV elicited high neutralizing antibody titers and broad T-cell responses in nonhuman primates. [Mol Ther Methods Clin Dev] Full Article

HIV

Lineage-Specific Viral Hijacking of Non-Canonical E3 Ubiquitin Ligase Cofactors in the Evolution of Vif Anti-APOBEC3 Activity
Scientists employed a comparative approach combining proteomic, biochemical, structural, and virological techniques to investigate Vif complexes across the lentivirus genus, including primate (HIV-1 and simian immunodeficiency virus macaque) and non-primate (FIV, BIV, and MVV) viruses. [Cell Rep]
Full Article | Graphical Abstract

A Two-Year Follow-Up of Macaques Developing Intermittent Control of the HIV Homolog SIVmac251 in the Chronic Phase of the Infection
Scientists previously showed that a combination of highly suppressive antiretroviral therapy and two experimental drugs was able to reduce the viral reservoir, elicit efficient cell-mediated antiviral responses, and induce intermittent post-therapy viral load control in chronically SIVmac251-infected macaques. They now show that the macaques that had received this drug combination and then stopped antiretroviral therapy were also able to maintain low numbers of activated CD4⁺ T-cells at viral rebound. [J Virol] Abstract

HIV-1 Env and Nef Cooperatively Contribute to pDCs Activation via CD4-Dependent Mechanisms
Investigators report that two genetically similar HIV-1 (R3A and R3B) variants isolated from a rapid progressor differentially activated plasmacytoid dendritic cells (pDCs) to produce IFNα. The highly pathogenic R3A efficiently activated pDCs to induce robust IFNα production, while the less pathogenic R3B did not. [J Virol] Abstract

A Broad Range of Mutations in HIV-1 Neutralizing Human Monoclonal Antibodies Specific for V2, V3, and the CD4 Binding Site
To determine the range of neutralization mediated by human monoclonal antibodies (mAbs) similar to HIV vaccine-induced neutralizing Abs but derived from unselected chronically HIV-1 infected subjects, researchers tested a panel of 66 mAbs specific to V3, CD4 binding site and V2 regions. [Mol Immunol] Abstract

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Innate Immunity against HIV-1 Infection
The concerted actions of PRR signaling, specific viral-restriction factors, innate immune cells, innate-adaptive immune crosstalk and viral evasion strategies determine the outcome of HIV-1 infection and immune responses. [Nat Immunol] Abstract

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Lakewood-Amedex Announces Its Novel Bisphospocin^® Class of Antimicrobials Kills Multidrug Resistant-Tuberculosis (MDR-TB) Strains In Fifteen Minutes
Lakewood-Amedex Inc. announced that a recent series of in vitro studies conducted by Southern Research in Birmingham, Alabama, have demonstrated that its novel class of antimicrobials, named bisphosphocins, have proven effective at killing MDR-TB, the bacteria responsible for the chronic lung infection tuberculosis. [Lakewood-Amedex Inc. (PR Newswire Association LLC)] Press Release

Persistence Yields Progress in AIDS Vaccine Research at UC Santa Cruz
Phil Berman has established a major vaccine research effort funded by a series of grants from the National Institutes of Health, including two new grants in 2014 totaling $2.6 million. The latest results from this effort have Berman sounding optimistic about the prospects for a vaccine that can be effective in protecting against HIV infection. [UC Santa Cruz] Press Release | Video

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