Dynamics of Natural Killer cell receptor revealed by quantitative analysis of photoswitchable protein

Natural Killer (NK) cell activation is dynamically regulated by numerous activating and inhibitory surface receptors that accumulate at the immune synapse. Quantitative analysis of receptor dynamics has been limited by methodologies which rely on indirect measurements such as fluorescence recovery after photobleaching. Here, we report a novel approach to study how proteins traffic to and from the immune synapse using NK cell receptors tagged with the photoswitchable fluorescent protein tdEosFP, which can be irreversibly photoswitched from a green to red fluorescent state by ultraviolet light. Thus, following a localized switching event, the movement of the photoswitched molecules can be temporally and spatially resolved by monitoring fluorescence in two regions of interest. By comparing images with mathematical models, we evaluated the diffusion coefficient of the receptor KIR2DL1 (0.23 +- 0.06 micron^2/s) and assessed how synapse formation affects receptor dynamics. Our data conclude that the inhibitory NK cell receptor KIR2DL1 is continually trafficked into the synapse and remains surprisingly stable there. Unexpectedly however, in NK cells forming synapses with multiple target cells simultaneously, KIR2DL1 at one synapse can relocate to another synapse. Thus, our results reveal a previously undetected inter-synaptic exchange of protein.Comment: 25 pages, 5 figure

Red wine polyphenols prevent metabolic and cardiovascular alterations associated with obesity in Zucker fatty rats (Fa/Fa)

Peer reviewedPublisher PD

The evolutionary ecology of complex lifecycle parasites: linking phenomena with mechanisms

Many parasitic infections, including those of humans, are caused by complex lifecycle parasites (CLPs): parasites that sequentially infect different hosts over the course of their lifecycle. CLPs come from a wide range of taxonomic groups-from single-celled bacteria to multicellular flatworms-yet share many common features in their life histories. Theory tells us when CLPs should be favoured by selection, but more empirical studies are required in order to quantify the costs and benefits of having a complex lifecycle, especially in parasites that facultatively vary their lifecycle complexity. In this article, we identify ecological conditions that favour CLPs over their simple lifecycle counterparts and highlight how a complex lifecycle can alter transmission rate and trade-offs between growth and reproduction. We show that CLPs participate in dynamic host-parasite coevolution, as more mobile hosts can fuel CLP adaptation to less mobile hosts. Then, we argue that a more general understanding of the evolutionary ecology of CLPs is essential for the development of effective frameworks to manage the many diseases they cause. More research is needed identifying the genetics of infection mechanisms used by CLPs, particularly into the role of gene duplication and neofunctionalisation in lifecycle evolution. We propose that testing for signatures of selection in infection genes will reveal much about how and when complex lifecycles evolved, and will help quantify complex patterns of coevolution between CLPs and their various hosts. Finally, we emphasise four key areas where new research approaches will provide fertile opportunities to advance this field

Pathophysiological lessons from rare associations of immunological disorders

Rare associations of immunological disorders can often tell more than mice and rats about the pathogenesis of immunologically mediated human kidney disease. Cases of glomerular disease with thyroiditis and Graves’ disease and of minimal change disease with lymphoepithelioma-like thymic carcinoma and lymphomatoid papulosis were recently reported in Pediatric Nephrology. These rare associations can contribute to the unraveling of the pathogenesis of membranous nephropathy (MN) and minimal change disease (MCD) and lead to the testing of novel research hypotheses. In MN, the target antigen may be thyroglobulin or another thyroid-released antigen that becomes planted in the glomerulus, but other scenarios can be envisaged, including epitope spreading, polyreactivity of pathogenic antibodies, and dysregulation of T regulatory cells, leading to the production of a variety of auto-antibodies with different specificities [immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX syndrome)]. The occurrence of MCD with hemopathies supports the role of T cells in the pathogenesis of proteinuria, although the characteristics of those T cells remain to be established and the glomerular permeability factor(s) identified

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Le rôle des activités physiques et sportives dans l'aide à l'arrêt du tabac

Le sport pour lutter contre les effets secondaires du sevrage