HLA-E-Restricted Cross-Recognition of Allogeneic Endothelial Cells by CMV-Associated CD8 T Cells: A Potential Risk Factor following Transplantation

Although association between CMV infection and allograft rejection is well admitted, the precise mechanisms involved remain uncertain. Here, we report the characterization of an alloreactive HLA-E-restricted CD8 T cell population that was detected in the PBL of a kidney transplant patient after its CMV conversion. This monoclonal CD8 T cell population represents a sizable fraction in the blood (3% of PBL) and is characterized by an effector-memory phenotype and the expression of multiple NK receptors. Interestingly, these unconventional T cells display HLA-E-dependent reactivity against peptides derived from the leader sequences of both various HCMV-UL40 and allogeneic classical HLA-I molecules. Consequently, while HLA-E-restricted CD8 T cells have potential to contribute to the control of CMV infection in vivo, they may also directly mediate graft rejection through recognition of peptides derived from allogeneic HLA-I molecules on graft cells. Therefore, as HLA-E expression in nonlymphoid organs is mainly restricted to endothelial cells, we investigated the reactivity of this HLA-E-restricted T cell population towards allogeneic endothelial cells. We clearly demonstrated that CMV-associated HLA-E-restricted T cells efficiently recognized and killed allogeneic endothelial cells in vitro. Moreover, our data indicate that this alloreactivity is tightly regulated by NK receptors, especially by inhibitory KIR2DL2 that strongly prevents TCR-induced activation through recognition of HLA-C molecules. Hence, a better evaluation of the role of CMV-associated HLA-E-restricted T cells in transplantation and of the impact of HLA-genotype, especially HLA-C, on their alloreactivity may determine whether they indeed represent a risk factor following organ transplantation.     

Glycosaminoglycans Are Interactants of Langerin: Comparison with gp120 Highlights an Unexpected Calcium-Independent Binding Mode

Langerin is a C-type lectin specifically expressed in Langerhans cells. As recently shown for HIV, Langerin is thought to capture pathogens and mediate their internalisation into Birbeck Granules for elimination. However, the precise functions of Langerin remain elusive, mostly because of the lack of information on its binding properties and physiological ligands. Based on recent reports that Langerin binds to sulfated sugars, we conducted here a comparative analysis of Langerin interaction with mannose-rich HIV glycoprotein gp120 and glycosaminoglycan (GAGs), a family of sulfated polysaccharides expressed at the surface of most mammalian cells. Our results first revealed that Langerin bound to these different glycans through very distinct mechanisms and led to the identification of a novel, GAG-specific binding mode within Langerin. In contrast to the canonical lectin domain, this new binding site showed no Ca²⁺-dependency, and could only be detected in entire, trimeric extracellular domains of Langerin. Interestingly binding to GAGs, did not simply rely on a net charge effect, but rather on more discrete saccharide features, such as 6-O-sulfation, or iduronic acid content. Using molecular modelling simulations, we proposed a model of Langerin/heparin complex, which located the GAG binding site at the interface of two of the three Carbohydrate-recognition domains of the protein, at the edge of the a-helix coiled-coil. To our knowledge, the binding properties that we have highlighted here for Langerin, have never been reported for C-type lectins before. These findings provide new insights towards the understanding of Langerin biological functions.     

Urban biodiversity, city-dwellers and conservation: how does an outdoor activity day affect the human-nature relationship?

Urban conservation education programs aim to increase knowledge and awareness towards biodiversity and to change attitudes and behaviour towards the environment. However, to date, few urban conservation education studies have evaluated to what extent these programs have managed to achieve their goals. In this study, we experimentally explored the influence of an urban conservation activity day on individual knowledge, awareness and actions towards biodiversity, in both the short and longer term.We organised three activity days in Paris (France), during which people were invited to participate in urban conservation efforts. Both quantitative (questionnaire) and qualitative (interviews) methods were employed to investigate the influence of this short urban nature experience on the relationships that city-dwellers develop with nearby biodiversity. We found a strong positive correlation between the levels of participation and an immediate interest towards local urban biodiversity. In the longer term, however, although participants claimed to have gained more knowledge, local awareness and interest for species in their daily environment, they did not seem to extend this interest to participating in other related activities. These results highlight the complexity of validating the effectiveness of this type of education program for achieving conservation goals. Although such a short activity may only have a limited environmental impact, it nevertheless seems to increase people's knowledge, awareness, interest and concern. We therefore believe that when repeated locally, these short conservation education programs could enhance people's experience with nature in cities and achieve conservation goals more fully.     

Systematics,palaeoecology and palaeobiogeography of the Neogene fossil sharks from the Azores (Northeast Atlantic)

The Azores Archipelago is a group of isolated islands located in the North Atlantic Ocean. One of these oceanic islands – Santa Maria – exhibits marine fossiliferous sediments of late Miocene/early Pliocene and also of Pleistocene age. Recent research provided new selachian fossil material, with three new records (Carcharias acutissima, Megaselachus megalodon, and Carcharhinus cf. leucas) increasing the number of fossil sharks reported from the Azores (Santa Maria Island) to seven species (Notorynchus primigenius, C. acutissima, Cosmopolitodus hastalis, Paratodus benedenii, Isurus oxyrinchus, M. megalodon, and C. cf. leucas). So far, no teeth of batoids or small sharks have been found despite the screen-washing of several sediment samples from Santa Maria. The Azorean Mio-Pliocene selachian fauna clearly differs from those described from sediments deposited on continental shelves, in which batoids and small benthic sharks (e.g., scyliorhinids) are usually well represented. During the late Miocene/early Pliocene, subtropical to warm-temperate seas were prevalent in the area of the Azores, as deduced from palaeontological, geological and isotopic data, all indicating a warmer climate than in the present.     

Spatial heterogeneity in mortality and its impact on the population dynamics of Eurasian woodcocks

Spatial heterogeneity, especially in mortality risk, is a major factor shaping population dynamics. Here we study the impacts of spatial heterogeneity in hunting pressure on the demography of Eurasian woodcock Scolopax rusticola, a relatively long-lived migratory game bird. We develop capture–recapture–recovery models in which both seasonality and spatial variation in hunting pressure are accounted for, and fit them to individual-based data collected across the French wintering range (>44000 banded individuals) as well as recoveries from spring stopovers and breeding grounds in Europe. Our results quantify spatial variation in survival probability in the wintering areas. They highlight the role of source-sink dynamics involving juvenile settlement decisions, as well as the importance of mortality outside the winter quarters. We also discuss the impact of spatial heterogeneity for demographic parameter estimation and data collection at the range scale.     

COEVOLUTION BETWEEN MATERNAL TRANSFER OF IMMUNITY AND OTHER RESISTANCE STRATEGIES AGAINST PATHOGENS

Among the wide variety of resistance mechanisms to parasitism, the transgenerational transfer of immunity from mother to offspring has largely been overlooked and never included in evolutionary or coevolutionary studies of resistance mechanisms. Here we study the evolution and coevolution of various resistance mechanisms with a special focus on maternal transfer of immunity. In particular we show that maternal transfer of immunity is only expected to evolve when cross immunity is high and when the pathogens have an intermediate virulence. We also show that the outcome of the coevolution between various resistance mechanisms depends critically on the life span of the host. We predict that short‐lived species should invest in avoidance strategies, whereas long‐lived species should invest in acquired resistance mechanisms. These results may help understanding the diversity of resistance strategies that have evolved in vertebrate species. Our framework also provides a general basis for the study of the evolution of other transgenerational resistance mechanisms.