DNA immunization with predicted T-cell epitopes protects against lethal SARS-CoV-2 infection in K18-hACE2 mice.

The global SARS-CoV-2 pandemic caused significant social and economic disruption worldwide, despite highly effective vaccines being developed at an unprecedented speed. Because the first licensed vaccines target only single B-cell antigens, antigenic drift could lead to loss of efficacy against emerging SARS-CoV-2 variants. Improving B-cell vaccines by including multiple T-cell epitopes could solve this problem.

Vitamin D and the Ability to Produce 1,25(OH)D Are Critical for Protection from Viral Infection of the Lungs.

Vitamin D supplementation is linked to improved outcomes from respiratory virus infection, and the COVID-19 pandemic renewed interest in understanding the potential role of vitamin D in protecting the lung from viral infections. Therefore, we evaluated the role of vitamin D using animal models of pandemic H1N1 influenza and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. In mice, dietary-induced vitamin D deficiency resulted in lung inflammation that was present prior to infection.

Macrophage Selenoproteins Restrict Intracellular Replication of and Are Essential for Host Immunity.

The essential micronutrient Selenium (Se) is co-translationally incorporated as selenocysteine into proteins. Selenoproteins contain one or more selenocysteines and are vital for optimum immunity. Interestingly, many pathogenic bacteria utilize Se for various biological processes suggesting that Se may play a role in bacterial pathogenesis.

The bacterial siderophore enterobactin confers survival advantage to in macrophages.

Enterobactin (Ent), a prototypical bacterial siderophore known for its unparalleled affinity for iron, is widely conserved among members of the family of Gram-negative bacteria. In this study, we demonstrated that, aside from mediating iron acquisition, Ent also dampened the macrophages (MΦs) antimicrobial responses against intracellular infection by serovar Typhimurium. Accordingly, the loss of Ent expression () in demoted their survivability against MΦs.

Development of a novel Francisella tularensis Live Vaccine Strain expressing ovalbumin provides insight into antigen-specific CD8+ T cell responses.

Progress towards a safe and effective vaccine for the prevention of tularemia has been hindered by a lack of knowledge regarding the correlates of protective adaptive immunity and a lack of tools to generate this knowledge. CD8+ T cells are essential for protective immunity against virulent strains of Francisella tularensis, but to-date, it has not been possible to study these cells in an antigen-specific manner. Here, we report the development of a tool for expression of the model antigen ovalbumin (OVA) in F.

Inhibitors of Ribosome Rescue Arrest Growth of Francisella tularensis at All Stages of Intracellular Replication.

Bacteria require at least one pathway to rescue ribosomes stalled at the ends of mRNAs. The primary pathway for ribosome rescue is trans-translation, which is conserved in >99% of sequenced bacterial genomes. Some species also have backup systems, such as ArfA or ArfB, which can rescue ribosomes in the absence of sufficient trans-translation activity.

The Syk-binding ubiquitin ligase c-Cbl mediates signaling-dependent B cell receptor ubiquitination and B cell receptor-mediated antigen processing and presentation.

B cell receptor (BCR)-mediated antigen (Ag) processing and presentation lead to B cell-T cell interactions, which support affinity maturation and immunoglobulin class switching. These interactions are supported by generation of peptide-MHC class II complexes in multivesicular body-like MIIC compartments of B cells. Previous studies have shown that trafficking of Ag·BCR complexes to MVB-like MIIC occurs via an ubiquitin-dependent pathway and that ubiquitination of Ag·BCR complexes occurs by an Src family kinase signaling-dependent mechanism that is restricted to lipid raft-resident Ag·BCR complexes.

Physiological-range temperature changes modulate cognate antigen processing and presentation mediated by lipid raft-restricted ubiquitinated B cell receptor molecules.

BCR-mediated Ag processing and presentation is critical to the initiation and control of a humoral immune response. Trafficking of internalized Ag-BCR complexes to intracellular Ag processing compartments is driven by ubiquitination of the cytoplasmic domain of the BCR. Using a biochemical approach, it is here established that ubiquitinated Ag-BCR complexes are formed via a signaling-dependent mechanism and restricted to plasma membrane lipid rafts.

Francisella tularensis induces ubiquitin-dependent major histocompatibility complex class II degradation in activated macrophages.

The intracellular bacterium Francisella tularensis survives and replicates within macrophages, ultimately killing the host cell. Resolution of infection requires the development of adaptive immunity through presentation of F. tularensis antigens to CD4+ and CD8+ T cells.

Functional and structural requirements for the internalization of distinct BCR-ligand complexes.

Antigen (Ag) binding to the BCR rapidly initiates two important events: a phosphorylation cascade that results in the production of secondary signaling intermediaries and the internalization of Ag-BCR complexes. Previous studies using anti-BCR antibodies (Ab) have suggested that BCR signaling is an essential requirement for BCR endocytosis and have further implicated lipid rafts as essential platforms for both BCR functions. However, published data from our laboratory indicate that lipid rafts and consequently raft-mediated signaling are dispensable for BCR-mediated internalization of Ag-specific BCR.