Immunology of Infectious Disease News Volume 3.12 | Apr 1 2015

Prostaglandin E2 and Programmed Cell Death 1 Signaling Coordinately Impair CTL Function and Survival during Chronic Viral Infection
Researchers found that the prostaglandin E2 receptors EP2 and EP4 were upregulated on virus-specific cytotoxic T lymphocytes (CTLs) during chronic lymphocytic choriomeningitis virus infection and suppressed CTL survival and function. [Nat Med] Abstract | Press Release

T Cell Lipid Peroxidation Induces Ferroptosis and Prevents Immunity to Infection
Scientists investigated the importance of glutathione peroxidase 4 (Gpx4) for physiological T cell responses by using T cell-specific Gpx4-deficient mice. Their results revealed that, despite normal thymic T cell development, CD8⁺ T cells from T^{ΔGpx4/ΔGpx4} mice had an intrinsic defect in maintaining homeostatic balance in the periphery. [J Exp Med] Abstract

Autophagy Mediates Tolerance to Staphylococcus aureus Alpha-Toxin
Researchers found that the dominant function of autophagy proteins during infections with the epidemic community-associated methicillin-resistant S. aureus USA300 is to mediate tolerance rather than resistance. Atg16L1 hypomorphic mice, which have reduced autophagy, were highly susceptible to lethality in both sepsis and pneumonia models of USA300 infection. [Cell Host Microbe] Abstract | Graphical Abstract

Trained Immunity in Newborn Infants of HBV-Infected Mothers
Scientists demonstrated that Hepatitis B virus (HBV) exposure in utero triggered a state of trained immunity, characterized by innate immune cell maturation and Th1 development, which in turn enhanced the ability of cord blood immune cells to respond to bacterial infection in vitro. [Nat Commun] Full Article | Press Release

HIV

Ex Vivo Analysis Identifies Effective HIV-1 Latency-Reversing Drug Combinations
Using resting CD4⁺ T cells from infected individuals, scientists developed an experimental and theoretical framework to identify effective latency-reversing agent (LRA) combinations. Utilizing ex vivo assays for intracellular HIV-1 mRNA and virion production, they compared two-drug combinations of leading candidate LRAs and identified multiple combinations that effectively reverse latency. [J Clin Invest]
Full Article | Press Release

Compartmentalized Replication of R5 T Cell-Tropic HIV-1 in the Central Nervous System Early in the Course of Infection
Investigators examined the frequency of elevated cerebrospinal fluid (CSF) HIV-1 RNA concentration, the nature of CSF viral populations compared to the blood, and the presence of a cellular inflammatory response (with the potential to bring infected cells into the central nervous system) using paired CSF and blood samples obtained over the first two years of infection from 72 ART-naïve subjects. [PLoS Pathog] Full Article | Press Release

Decreased HIV-Specific T-Regulatory Responses Are Associated with Effective DC-Vaccine Induced Immunity
Scientists reported that vaccination with ex vivo-generated dendritic-cells (DC) loaded with HIV-lipopeptides in HIV-infected patients was well tolerated and highly immunogenic. [PLoS Pathog] Full Article

Colorectal Mucus Binds DC-SIGN and Inhibits HIV-1 Trans-Infection of CD4⁺ T-Lymphocytes
Colorectal mucus from a number of individuals was collected and tested for the capacity to bind DC-SIGN and inhibit HIV-1 cis– or trans-infection of CD4⁺ T-lymphocytes. [PLoS One] Full Article

Persistence of Pathological Distribution of NK Cells in HIV-Infected Patients with Prolonged Use of HAART and a Sustained Immune Response
Investigators conducted a prospective analysis of the distribution of NK subsets and natural cytotoxicity receptors in HIV patients with long-term HAART use and sustained virological and immunological response. [PLoS One] Full Article

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Immune Response BioPharma, Inc. Announces the FDA has Accepted REMUNE HIV/AIDS Vaccine BLA for Review
Immune Response BioPharma, Inc. provided an update on REMUNE and announced the FDA has accepted the REMUNE HIV/AIDS vaccine BLA (biologics licensing application) for review for therapeutic treatment in adults with HIV/AIDS. [Immune Response BioPharma, Inc. (PRLog)] Press Release

Sanofi Pasteur Announces FDA Approval of Quadracel DTaP-IPV Vaccine for Children Four through Six Years of Age
Sanofi Pasteur announced that the U.S. Food and Drug Administration (FDA) has approved use of Quadracel™ vaccine for active immunization against diphtheria, tetanus, pertussis and poliomyelitis in children four through six years of age. [Sanofi Pasteur SA] Press Release

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