Immunology of Infectious Disease News Volume 3.40 | Oct 21 2015

Tuberculosis Is Associated with Expansion of a Motile, Permissive and Immunomodulatory CD16⁺ Monocyte Population via the IL-10/STAT3 Axis
In the context of active tuberculosis, investigators demonstrated that human monocytes are predisposed to differentiate towards an anti-inflammatory macrophage activation program characterized by the CD16⁺CD163⁺MerTK⁺pSTAT3⁺ phenotype and functional properties such as enhanced protease-dependent motility, pathogen permissivity and immunomodulation. [Cell Res] Abstract

Group A Streptococcal M1 Protein Sequesters Cathelicidin to Evade Innate Immune Killing
Researchers showed that the group A Streptococcus (GAS) surface-associated M1 protein sequesters and neutralizes LL-37 antimicrobial activity through its N-terminal domain. Exogenous M1 protein rescues M1-deficient GAS from killing by neutrophils and within neutrophil extracellular traps and neutralizes LL-37 chemotactic properties. [Cell Host Microbe] Abstract | Graphical Abstract | Press Release

Maternal CD4⁺ T Cells Protect against Severe Congenital Cytomegalovirus Disease in a Novel Nonhuman Primate Model of Placental Cytomegalovirus Transmission
Using a novel nonhuman primate model of congenital cytomegalovirus transmission, scientists demonstrated a critical role for maternal CD4⁺ T cells in the induction of protective maternal immune responses that prevent fetal demise. [Proc Natl Acad Sci USA] Abstract | Press Release

HIV

Activation and Lysis of Human CD4 Cells Latently Infected with HIV-1
An immunomodulatory protein was created that combines the specificity of a HIV-1 broadly neutralizing antibody with that of an antibody to the CD3 component of the T-cell receptor. CD3 engagement by the protein can stimulate T-cell activation that induces proviral gene expression in latently infected T cells. [Nat Commun] Full Article | Press Release

Follicular Regulatory T Cells Impair Follicular T Helper Cells in HIV and SIV Infection
Utilizing both human and rhesus macaque models, scientists showed the impact of HIV and SIV infection on follicular regulatory T cells (T_FR) number and function. They found that T_FR proportionately and numerically expand during infection through mechanisms involving viral entry and replication, TGF-β signaling, low apoptosis rates and the presence of regulatory dendritic cells. [Nat Commun] Full Article

CD4⁺ T Cell–Dependent and CD4⁺ T Cell–Independent Cytokine-Chemokine Network Changes in the Immune Responses of HIV-Infected Individuals
Researchers hypothesized that there were CD4⁺ T cell–dependent and CD4⁺ T cell–independent alterations in the immune responses of HIV-1⁺ individuals. To test this, they analyzed the secretion of cytokines and chemokines from stimulated peripheral blood mononuclear cell populations from HIV⁺ donors, healthy donors, and healthy donors with CD4⁺ T cells experimentally depleted. [Sci Signal] Abstract

The Mixed Lineage Kinase-3 Inhibitor URMC-099 Improves Therapeutic Outcomes for Long-Acting Antiretroviral Therapy
Long-acting ritonavir-boosted atazanavir nanoformulations co-administered with URMC-099 reduced viral load and the numbers of HIV-1 infected CD4⁺ T-cells in lymphoid tissues more than either drug alone in infected humanized NOD/SCID/IL2Rγc^−/− mice. [Nanomedicine] Abstract | Press Release

Genome Editing of CXCR4 by CRISPR/cas9 Confers Cells Resistant to HIV-1 Infection
Scientists showed that human CXCR4 gene is efficiently disrupted by CRISPR/Cas9-mediated genome editing, leading to human immunodeficiency virus type 1 (HIV-1) resistance of human primary CD4⁺ T cells. [Sci Rep] Full Article

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Inovio and Partner Advance MERS Vaccine
GeneOne Life Science Inc., which partnered with Inovio Pharmaceuticals, Inc. to develop Inovio’s MERS vaccine (GLS-5300), announced the filing of an Investigational New Drug Application for GLS-5300 with the United States Food and Drug Administration. [Inovio Pharmaceuticals, Inc.] Press Release

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