The pathogenesis of low pathogenicity H7 avian influenza viruses in chickens, ducks and turkeys

<p>Abstract</p> <p>Background</p> <p>Avian influenza (AI) viruses infect numerous avian species, and low pathogenicity (LP) AI viruses of the H7 subtype are typically reported to produce mild or subclinical infections in both wild aquatic birds and domestic poultry. However relatively little work has been done to compare LPAI viruses from different avian species for their ability to cause disease in domestic poultry under the same conditions. In this study twelve H7 LPAI virus isolates from North America were each evaluated for their comparative pathogenesis in chickens, ducks, and turkeys.</p> <p>Results</p> <p>All 12 isolates were able to infect all three species at a dose of 10⁶50% egg infectious doses based on seroconversion, although not all animals seroconverted with each isolate-species combination. The severity of disease varied among isolate and species combinations, but there was a consistent trend for clinical disease to be most severe in turkeys where all 12 isolates induced disease, and mortality was observed in turkeys exposed to 9 of the 12 viruses. Turkeys also shed virus by the oral and cloacal routes at significantly higher titers than either ducks or chickens at numerous time points. Only 3 isolates induced observable clinical disease in ducks and only 6 isolates induced disease in chickens, which was generally very mild and did not result in mortality. Full genome sequence was completed for all 12 isolates and some isolates did have features consistent with adaptation to poultry (e.g. NA stalk deletions), however none of these features correlated with disease severity.</p> <p>Conclusions</p> <p>The data suggests that turkeys may be more susceptible to clinical disease from the H7 LPAI viruses included in this study than either chickens or ducks. However the severity of disease and degree of virus shed was not clearly correlated with any isolate or group of isolates, but relied on specific species and isolate combinations.</p

Lipid accumulation and dendritic cell dysfunction in cancer

Professional antigen presenting cells, dendritic cells (DC) are responsible for initiation and maintenance of immune responses. Here, we report that a substantial proportion of DCs in tumor-bearing mice and cancer patients have increased levels of triglycerides. Lipid accumulation in DCs was caused by increased uptake of extracellular lipids due to up-regulation of scavenger receptor A. DCs with high lipid content were not able to effectively stimulate allogeneic T cells or present tumor-associated antigens. DCs with high and normal lipid levels did not differ in expression of MHC and co-stimulatory molecules. However, lipid-laden DCs had reduced capacity to process antigens. Pharmacological normalization of lipid levels in DCs with an inhibitor of acetyl-CoA carboxylase restored the functional activity of DCs and substantially enhanced the effects of a cancer vaccine. These findings support the regulation of immune responses in cancer by manipulation of lipid levels in DCs

Kinetics and binding capacity of six soils for structurally defined hydrolyzable and condensed tannins and related phenols

We investigated tannin–soil interactions by assessing the kinetics of sorption and sorption capacities, and their relationship to the chemical properties of six polyphenolic compounds and the textures of six soils. We developed a new extraction procedure for recovering tannins from soil samples by successive extraction with solvents of decreasing polarity.Sorption of polyphenolic compounds methyl gallate, catechin, oenothein B, pentagalloyl glucose, epigallocatechin gallate, and procyanidin dimer was determined using six soils with textures ranging from 7% silt–89% sand to 52% silt–22% sand. Sorption kinetics and capacity of the soils were determined using room temperature mixing with high performance liquid chromatography (HPLC) to determine polyphenol concentration. Tannins were extracted from soils loaded with known amounts of the model compounds using solvents with a range of polarities, and establishing recovery by HPLC. Multivariable regression was used to establish relationships between polyphenol properties and sorption, and between soil texture and sorption.Sorption of the polyphenols followed the Langmuir isotherm with unique binding capacity and kinetics of sorption for each compound. Tannin sorption was correlated to molecular weight and polarity. For an Ultisol pasture soil, up to 18.7 mg g−1 soil of the large, hydrophobic compound epigallocatechin gallate was bound compared to only 5.11 mg g−1 soil of the smaller, more polar compound methyl gallate. Kinetics of sorption also varied with sorption reaching equilibrium between 75 and 350 min. Silt and sand composition affected polyphenol sorption in a unique fashion for each polyphenol. Using sequential extraction with solvents ranging from polar (water) to non-polar (hexane), we extracted up to 42% of the material that had been loaded on the soil as a mixture of five polyphenols.This work demonstrates that the likely fate of tannins and related polyphenols from plant sources is rapid sorption, with little likelihood of release of unmodified tannins from the soil by leaching. Tight sorption impedes recovery and analysis of soil tannins, but better methods for extraction may improve our knowledge of tannins in the soil