Low CCR7-Mediated Migration of Human Monocyte Derived Dendritic Cells in Response to Human Respiratory Syncytial Virus and Human Metapneumovirus

Human respiratory syncytial virus (HRSV) and, to a lesser extent, human metapneumovirus (HMPV) and human parainfluenza virus type 3 (HPIV3), can re-infect symptomatically throughout life without significant antigenic change, suggestive of incomplete or short-lived immunity. In contrast, re-infection by influenza A virus (IAV) largely depends on antigenic change, suggestive of more complete immunity. Antigen presentation by dendritic cells (DC) is critical in initiating the adaptive immune response. Antigen uptake by DC induces maturational changes that include decreased expression of the chemokine receptors CCR1, CCR2, and CCR5 that maintain DC residence in peripheral tissues, and increased expression of CCR7 that mediates the migration of antigen-bearing DC to lymphatic tissue. We stimulated human monocyte-derived DC (MDDC) with virus and found that, in contrast to HPIV3 and IAV, HMPV and HRSV did not efficiently decrease CCR1, 2, and 5 expression, and did not efficiently increase CCR7 expression. Consistent with the differences in CCR7 mRNA and protein expression, MDDC stimulated with HRSV or HMPV migrated less efficiently to the CCR7 ligand CCL19 than did IAV-stimulated MDDC. Using GFP-expressing recombinant virus, we showed that the subpopulation of MDDC that was robustly infected with HRSV was particularly inefficient in chemokine receptor modulation. HMPV- or HRSV-stimulated MDDC responded to secondary stimulation with bacterial lipopolysaccharide or with a cocktail of proinflammatory cytokines by increasing CCR7 and decreasing CCR1, 2 and 5 expression, and by more efficient migration to CCL19, suggesting that HMPV and HRSV suboptimally stimulate rather than irreversibly inhibit MDDC migration. This also suggests that the low concentration of proinflammatory cytokines released from HRSV- and HMPV-stimulated MDDC is partly responsible for the low CCR7-mediated migration. We propose that inefficient migration of HRSV- and HMPV-stimulated DC to lymphatic tissue contributes to reduced adaptive responses to these viruses

Mouse mammary stem cells express prognostic markers for triple-negative breast cancer

Introduction Triple negative breast cancer (TNBC) is a heterogeneous group of tumours in which chemotherapy, the current mainstay of systemic treatment, is often initially beneficial but with a high risk of relapse and metastasis. There is currently no means of predicting which TNBC will relapse. We tested the hypothesis that the biological properties of normal stem cells are re-activated in tumour metastasis and that, therefore, the activation of normal mammary stem cell-associated gene sets in primary TNBC would be highly prognostic for relapse and metastasis. Methods Mammary basal stem and myoepithelial cells were isolated by flow cytometry and tested in low dose transplant assays. Gene expression microarrays were used to establish expression profiles of the stem and myoepithelial populations; these were compared to each other and to our previously established mammary epithelial gene expression profiles. Stem cell genes were classified by Gene Ontology (GO) analysis and the expression of a subset analysed in the stem cell population at single cell resolution. Activation of stem cell genes was interrogated across different breast cancer cohorts and within specific subtypes and tested for clinical prognostic power. Results A set of 323 genes was identified that was expressed significantly more highly in the purified basal stem cells compared to all other cells of the mammary epithelium. 109 out of 323 genes had been associated with stem cell features in at least one other study in addition to our own, providing further support for their involvement in the biology of this cell type. GO analysis demonstrated an enrichment of these genes for an association with cell migration, cytoskeletal regulation and tissue morphogenesis, consistent with a role in invasion and metastasis. Single cell resolution analysis showed that individual cells co-expressed both epithelial- and mesenchymal-associated genes/proteins. Most strikingly, we demonstrated that strong activity of this stem cell gene set in TNBCs identified those tumours most likely to rapidly progress to metastasis. Conclusions Our findings support the hypothesis that the biological properties of normal stem cells are drivers of metastasis and that these properties can be used to stratify patients with a highly heterogeneous disease such as TNBC

NK cells and type 1 innate lymphoid cells: partners in host defense

Innate lymphoid cells (ILCs) are effectors and regulators of innate immunity and tissue modeling and repair. Researchers have identified subsets of ILCs with differing functional activities, capacities to produce cytokines and transcription factors required for development and function. Natural killer (NK) cells represent the prototypical member of the ILC family. Together with ILC1s, NK cells constitute group 1 ILCs, which are characterized by their capacity to produce interferon-γ and their functional dependence on the transcription factor T-bet. NK cells and ILC1s are developmentally distinct but share so many features that they are difficult to distinguish, particularly under conditions of infection and inflammation. Here we review current knowledge of NK cells and the various ILC1 subset

Wood pellets, what else? : Greenhouse gas parity times of European electricity from wood pellets produced in the south-eastern United States using different softwood feedstocks

Several EU countries import wood pellets from the south-eastern United States. The imported wood pellets are (co-)fired in power plants with the aim of reducing overall greenhouse gas (GHG) emissions from electricity and meeting EU renewable energy targets. To assess whether GHG emissions are reduced and on what timescale, we construct the GHG balance of wood-pellet electricity. This GHG balance consists of supply chain and combustion GHG emissions, carbon sequestration during biomass growth and avoided GHG emissions through replacing fossil electricity. We investigate wood pellets from four softwood feedstock types: small roundwood, commercial thinnings, harvest residues and mill residues. Per feedstock, the GHG balance of wood-pellet electricity is compared against those of alternative scenarios. Alternative scenarios are combinations of alternative fates of the feedstock materials, such as in-forest decomposition, or the production of paper or wood panels like oriented strand board (OSB). Alternative scenario composition depends on feedstock type and local demand for this feedstock. Results indicate that the GHG balance of wood-pellet electricity equals that of alternative scenarios within 0–21 years (the GHG parity time), after which wood-pellet electricity has sustained climate benefits. Parity times increase by a maximum of 12 years when varying key variables (emissions associated with paper and panels, soil carbon increase via feedstock decomposition, wood-pellet electricity supply chain emissions) within maximum plausible ranges. Using commercial thinnings, harvest residues or mill residues as feedstock leads to the shortest GHG parity times (0–6 years) and fastest GHG benefits from wood-pellet electricity. We find shorter GHG parity times than previous studies, for we use a novel approach that differentiates feedstocks and considers alternative scenarios based on (combinations of) alternative feedstock fates, rather than on alternative land uses. This novel approach is relevant for bioenergy derived from low-value feedstocks

Modeling the impacts of wood pellet demand on forest dynamics in southeastern United States

The export of wood pellets from the southeastern United States (USA) has grown significantly in recent years, following rising demand from Europe. Increased wood pellet demand could lead to spatially variable changes in timberland management and area in the USA. This study presents an assessment of the impacts of increasing wood pellet demand (an additional 11.6 Mt by 2030) on land-use dynamics, taking into account developments in other wood product markets as well as expected changes in other land uses. An economic model for the forest sector of the southeastern USA (SRTS) was linked to a land-use change model (PLUC) to identify potential locations of land-use change following scenarios of demand for pellets and other wood products. Projections show that in the absence of additional demand for wood pellets, natural timberland area is projected to decline by 450–15 000 km2 by 2030, mainly through urbanization and pine plantation establishment. Under the high wood pellet demand scenario, more (2000–7500 km2) natural timberland area is retained and more (8000–20 000 km2) pine plantation is established. Shifts from natural timberland to pine plantation occur predominantly in the Atlantic coastal region. Future work will assess the impact of projected transitions in natural timberland and pine plantations on biodiversity and carbon storage. This modeling framework can be applied for multiple scenarios and land-use projections to identify locations of timberland area changes for the whole southeastern USA, thereby informing the debate about potential impacts of wood pellet demand on land-use dynamics and environmental services