60 research outputs found

    Blocking TLR7- and TLR9-mediated IFN-α Production by Plasmacytoid Dendritic Cells Does Not Diminish Immune Activation in Early SIV Infection

    Get PDF
    Persistent production of type I interferon (IFN) by activated plasmacytoid dendritic cells (pDC) is a leading model to explain chronic immune activation in human immunodeficiency virus (HIV) infection but direct evidence for this is lacking. We used a dual antagonist of Toll-like receptor (TLR) 7 and TLR9 to selectively inhibit responses of pDC but not other mononuclear phagocytes to viral RNA prior to and for 8 weeks following pathogenic simian immunodeficiency virus (SIV) infection of rhesus macaques. We show that pDC are major but not exclusive producers of IFN-α that rapidly become unresponsive to virus stimulation following SIV infection, whereas myeloid DC gain the capacity to produce IFN-α, albeit at low levels. pDC mediate a marked but transient IFN-α response in lymph nodes during the acute phase that is blocked by administration of TLR7 and TLR9 antagonist without impacting pDC recruitment. TLR7 and TLR9 blockade did not impact virus load or the acute IFN-α response in plasma and had minimal effect on expression of IFN-stimulated genes in both blood and lymph node. TLR7 and TLR9 blockade did not prevent activation of memory CD4+ and CD8+ T cells in blood or lymph node but led to significant increases in proliferation of both subsets in blood following SIV infection. Our findings reveal that virus-mediated activation of pDC through TLR7 and TLR9 contributes to substantial but transient IFN-α production following pathogenic SIV infection. However, the data indicate that pDC activation and IFN-α production are unlikely to be major factors in driving immune activation in early infection. Based on these findings therapeutic strategies aimed at blocking pDC function and IFN-α production may not reduce HIV-associated immunopathology. © 2013 Kader et al

    Hydraulics in the 21 st

    No full text

    Extreme Climatic events and Vegetation: the role of stabilizing processes

    No full text
    9 páginas, 2 figuras, 1 table.Current climatic trends involve both increasing temperatures and climatic variability, with extreme events becoming more frequent. Increasing concern on extreme climatic events has triggered research on vegetation shifts. However, evidences of vegetation shifts resulting from these events are still relatively rare. Empirical evidence supports the existence of stabilizing processes minimizing and counteracting the effects of these events, reinforcing community resilience. We propose a demographic framework to understand this inertia to change based on the balance between adult mortality induced by the event and enhanced recruitment or adult survival after the event. The stabilizing processes potentially contributing to this compensation include attenuation of the adult mortality caused by the event, due to site quality variability, to tolerance, phenotypic variability, and plasticity at population level, and to facilitative interactions. Mortality compensation may also occur by increasing future survival due to beneficial effect on growth and survival of the new conditions derived from global warming and increased climatic variability, to lowered competition resulting from reduced density in affected stands, or to antagonistic release when pathogens or predators are vulnerable to the event or the ongoing climatic conditions. Finally, mortality compensation may appear by enhanced recruitment due to release of competition with established vegetation, for instance as a consequence of gap openings after event-caused mortality, or to the new conditions, which may be more favorable for seedling establishment, or to enhanced mutualistic interactions (pollination, dispersal). There are important challenges imposed by the need of long-term studies, but a research agenda focused on potentially stabilizing processes is well suited to understand the variety of responses, including lack of sudden changes and community inertia that are frequently observed in vegetation under extreme events. This understanding is crucial for the establishment of sound management strategies and actions addressed to improve ecosystem resilience under climate change scenarios.The study was supported by projects of the Spanish Government (Consolider-Ingenio MontesCSD2008- 0040, CGL2006-26177E, CGL2007-60120, CGL2009-08101BOS, CGL2009-13190-C02-01BOS, CGL2009-07229BOS, CGL2010- 22180-C03-03, CGL2010-16373), by the Autonomous Communities of Catalonia (S2009/AMB-1783) and Madrid and the European Social Fund (REMEDINAL-2 S2009/AMB-1783).Peer reviewe

    Adapting forest health assessments to changing perspectives on threats – a case example from Sweden

    Get PDF
    A revised Swedish forest health assessment system is presented. The assessment system is composed of several interacting components which target information needs for strategic and operational decision making and accommodate a continuously expanding knowledge base. The main motivation for separating information for strategic and operational decision making is that major damage outbreaks are often scattered throughout the landscape. Generally, large-scale inventories (such as national forest inventories) cannot provide adequate information for mitigation measures. In addition to broad monitoring programs that provide time-series information on known damaging agents and their effects, there is also a need for local and regional inventories adapted to specific damage events. While information for decision making is the major focus of the health assessment system, the system also contributes to expanding the knowledge base of forest conditions. For example, the integrated monitoring programs provide a better understanding of ecological processes linked to forest health. The new health assessment system should be able to respond to the need for quick and reliable information and thus will be an important part of the future monitoring of Swedish forests
    corecore