Immunology of Infectious Disease News Volume 3.11 | Mar 25 2015

Calnexin Induces Expansion of Antigen-Specific CD4⁺ T Cells that Confer Immunity to Fungal Ascomycetes via Conserved Epitopes
Using transgenic CD4⁺ T cells recognizing this antigen, scientists identified an amino acid determinant within the chaperone calnexin that is conserved across diverse fungal ascomycetes. Infection with divergent ascomycetes, including dimorphic fungi, opportunistic molds, and the agent causing white nose syndrome in bats, induced expansion of calnexin-specific CD4⁺ T cells. [Cell Host Microbe] Abstract | Graphical Abstract

Apoptotic-Like Leishmania Exploit the Host’s Autophagy Machinery to Reduce T-Cell-Mediated Parasite Elimination
Macrophages infected with viable Leishmania induced proliferation of CD4⁺ T-cells, leading to a reduced intracellular parasite survival. Remarkably, the presence of apoptotic-like parasites in the inoculum significantly reduced T-cell proliferation. [Autophagy] 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

RSV Vaccine-Enhanced Disease Is Orchestrated by the Combined Actions of Distinct CD4 T Cell Subsets
The authors demonstrated for the first time that while CD4 T cells mediate all aspects of vaccine-enhanced disease, distinct CD4 T cell subsets orchestrated discrete and specific disease parameters. A Th2-biased immune response, but not eosinophils specifically, was required for airway hyperreactivity and mucus hypersecretion. [PLoS Pathog] Full Article

Programmed Death Ligand 1 on Burkholderia pseudomallei–Infected Human Polymorphonuclear Neutrophils Impairs T Cell Functions
Researchers examined the interaction of polymorphonuclear neutrophils (PMNs) and T cells in response to infection with B. pseudomallei, the causative agent of human melioidosis. They observed that CD4⁺ T cell proliferation and IFN-γ production in response to polyclonal activators was significantly inhibited by uninfected PMNs, and to a greater extent B. pseudomallei–infected PMNs. [J Immunol] Abstract

TLR2-Dependent ERK Signaling in Mycobacterium tuberculosis-Infected Macrophages Drives Anti-Inflammatory Responses and Inhibits Th1 Polarization of Responding T Cells
Investigators demonstrated that M. tuberculosis induction of IL-10, suppression of IL-12 and inhibition of class II major histocompatibility complex molecules in infected macrophages were all driven by Toll-like receptor 2 (TLR2)-dependent activation of the extracellular-signal-regulated kinases (ERK). [Infect Immun] Abstract

HIV

Clinical Outcome of HIV Viremic Controllers and Noncontrollers with Normal CD4 Counts Is Exclusively Determined by Antigen-Specific CD8⁺ T-Cell-Mediated HIV Suppression
Researchers evaluated T-cell responses using several assays to determine immune correlates of HIV control that distinguish untreated viremic controllers from noncontrollers with similar CD4 counts. [PLoS One] Full Article

Characterization of Functional Antibody and Memory B-Cell Responses to pH1N1 Monovalent Vaccine in HIV-Infected Children and Youth
Scientists investigated immune determinants of antibody responses and B-cell memory to pH1N1 vaccine in HIV-infected children. Ninety subjects received two double doses of pH1N1 vaccine. [PLoS One] Full Article

Recombinant Rubella Vectors Elicit SIV Gag-Specific T Cell Responses with Cytotoxic Potential in Rhesus Macaques
Investigators report that recombinant rubella vectors elicited robust de novo SIV-specific cellular immune responses detectable for greater than ten months even after a single vaccination. The antigen-specific responses induced by the rubella vector included central and effector memory CD4⁺ and CD8⁺ T cells with cytotoxic potential. [Vaccine] Full Article

Non-POU Domain-Containing Octamer-Binding Protein Negatively Regulates HIV-1 Infection in CD4⁺ T-Cells
Scientists investigated the effect of non-POU domain-containing octamer-binding protein (NonO) on HIV-1 life-cycle in CD4⁺ T-cell lines and primary CD4⁺ T-cells using single-cycle and replication-competent HIV-1 infection assays. They observed that shRNA-mediated stable NonO knockdown in CD4⁺ Jurkat T-cell line and primary CD4⁺ T-cells did not affect cell viability or proliferation, but enhanced HIV-1 infection. [AIDS Res Hum Retroviruses] Abstract

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T-Cell Exhaustion in Chronic Hepatitis B Infection: Current Knowledge and Clinical Significance
The review summarizes the current literature relevant to T-cell exhaustion in patients with hepatitis B virus (HBV)-related chronic hepatitis, the options for identifying new potential therapeutic targets to treat HBV infection and highlights priorities for further study. [Cell Death Dis] Full Article

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Baylor Researcher’s Hollow Fiber System TB Model Approved by European FDA Equivalent
The European Medicines Agency, the equivalent of the U.S. Food and Drug Administration (FDA), has approved the use of the hollow fiber system for the development of drugs to treat and prevent tuberculosis (TB). [Baylor Health Care System] Press Release

A Vaccine against Placental Malaria Made with ExpreS²ion Biotechnologies’ Protein Expression Technology, ExpreS², Is Ready to Start Human Tests in Germany and Benin
ExpreS²ion Biotechnologies announced the release by its partners at University of Copenhagen, of a vaccine candidate against the form of malaria that strikes pregnant women, for testing in humans. [ExpreS²ion Biotechnologies] Press Release

On the Way to a New Tuberculosis Vaccine
Scientists at the Max Planck Institute for Infection Biology in Berlin are working feverishly on a more effective replacement for Bacillus Calmette-Guérin. The vaccine candidate they have developed, dubbed VPM1002, will be tested in a large-scale Phase II trial with newborns. [Max-Planck Institute] Press Release

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