Expression of human TLR4/myeloid differentiation factor 2 directs an early innate immune response associated with modest increases in bacterial burden during infection.

Human TLR4 (hTLR4) and mouse TLR4 molecules respond differently to hypo-acylated LPS. The LPS of is hypo-acylated and heavily glycosylated and causes a minimal response by human cells. Thus, we hypothesized that mice expressing hTLR4 molecules would be more susceptible to infection.

Type I Interferon Counters or Promotes Coxiella burnetii Replication Dependent on Tissue.

Coxiella burnetii is an intracellular pathogen and the cause of Q fever. Gamma interferon (IFN-γ) is critical for host protection from infection, but a role for type I IFN in C. burnetii infection has not been determined.

Amphotericin B stimulates γδ T and NK cells, and enhances protection from Salmonella infection.

Amphotericin B (AmB) is a commonly used antifungal drug, with well-documented effects on cellular immune responses. We determined that AmB-stimulated γδ T-cell activation and proliferation in vitro at very low concentrations. AmB also enhanced IFN-γ production by NK cells in combination with IL-18.

Oral delivery of oligomeric procyanidins in Apple Poly® enhances type I IFN responses in vivo.

Type I IFN signaling is a central pathway that provides critical innate protection from viral and bacterial infection and can have regulatory outcomes in inflammatory settings. We determined previously that OPCs contained in the dietary supplement APP enhanced responses to type I IFN in vitro. Here, we confirm that OPCs from two different sources significantly increased pSTAT1, whereas a monomeric form of procyanidin did not.

Solute carrier 11A1 is expressed by innate lymphocytes and augments their activation.

Solute carrier 11A1 (SLC11A1) is a divalent ion transporter formerly known as the natural resistance-associated macrophage protein (NRAMP1) and the Bcg/Lsh/Ity locus. SLC11A1 was thought to be exclusively expressed in monocyte/macrophages and to have roles in phagosome maturation and cell activation. We characterized the expression of SLC11A1 in the majority of human and bovine γδ T cells and NK cells and in human CD3(+)CD45RO(+) T cells.

Oligomeric procyanidins stimulate innate antiviral immunity in dengue virus infected human PBMCs.

Oligomeric procyanidins (OPCs) have been shown to have antiviral and immunostimulatory effects. OPCs isolated from non-ripe apple peel were tested for capacity to reduce dengue virus (DENV) titers. Similar to published accounts, OPCs exhibited direct antiviral activity.

Polysaccharides derived from Yamoa (Funtumia elastica) prime gammadelta T cells in vitro and enhance innate immune responses in vivo.

Yamoa (ground bark of Funtumia elastica tree) is marketed and sold as a dietary supplement with anecdotal therapeutic effects in the treatment of asthma and hay fever. We determined that Yamoa and Yamoa-derived polysaccharides affected innate immunity, in part, by priming gammadelta T cells. Gene expression patterns in purified bovine gammadelta T cells and monocytes induced by Yamoa were similar to those induced by ultrapure lipopolysaccharide (uLPS).

Response of gammadelta T Cells to plant-derived tannins.

Many pharmaceutical drugs arc isolated from plants used in traditional medicines, and new plant-derived pharmaceutical drugs continue to be identified. Relevant to this review, different plant-derived agonists for gammadelta T cells are described that impart effector functions upon distinct subsets of these cells. Recently, plant tannins have been defined as one class of gammadelta T cell agonist and appear to preferentially activate the mucosal population.

Select plant tannins induce IL-2Ralpha up-regulation and augment cell division in gammadelta T cells.

Gammadelta T cells are innate immune cells that participate in host responses against many pathogens and cancers. Recently, phosphoantigen-based drugs, capable of expanding gammadelta T cells in vivo, entered clinical trials with the goal of enhancing innate immune system functions. Potential shortcomings of these drugs include the induction of nonresponsiveness upon repeated use and the expansion of only the Vdelta2 subset of human gammadelta T cells.

Recruitment of Tup1p and Cti6p regulates heme-deficient expression of Aft1p target genes.

In the budding yeast Saccharomyces cerevisiae, transcription of genes encoding for the high-affinity iron (FET3, FTR1) and copper (CTR1) transporters does not occur in the absence of heme. We show that the Aft1p binding region of the FET3 promoter or the Mac1p binding region of the CTR1 promoter is necessary and sufficient to mediate heme-deficient repression. Transcription is repressed in the absence of heme, and a genetic screen identified Tup1p and Hda1p as being required for transcriptional repression.

Binding linkage in a telomere DNA-protein complex at the ends of Oxytricha nova chromosomes.

Alpha and beta protein subunits of the telomere end binding protein from Oxytricha nova (OnTEBP) combine with telomere single strand DNA to form a protective cap at the ends of chromosomes. We tested how protein-protein interactions seen in the co-crystal structure relate to DNA binding through use of fusion proteins engineered as different combinations of domains and subunits derived from OnTEBP. Joining alpha and beta resulted in a protein that bound single strand telomere DNA with high affinity (K(D-DNA)=1.