Le récepteur TREM-1 (Triggering Receptor Expressed on Myeloid cells-1) joue un rôle crucial dans la mise en place du sepsis en amplifiant la réponse immunitaire de l'hôte. TLT-1 (TREM-Like Transcript-1) appartient à la famille des récepteurs TREMs, est exprimé exclusivement sur les plaquettes activées et est connu pour faciliter l'agrégation plaquettaire en liant le fibrinogène. Ces travaux montrent qu'une forme soluble de TLT-1 est impliquée dans la régulation de l'inflammation au cours du sepsis en modulant l'activation leucocytaire et le dialogue plaquette-neutrophile. Un peptide de 17 acides aminés issu de sa portion extracellulaire est porteur de cette activité par compétition avec le ligand de TREM-1. Alors que l'administration tant précoce que tardive de LR17 au cours du sepsis expérimental murin augmentait la survie, les animaux KO TLT-1 étaient hautement susceptibles à l'infection. Nous avons identifié ici un récepteur soluble libéré au cours de l'activation plaquettaire comme un potentiel régulateur de la réaction inflammatoire au cours du sepsis, ouvrant ainsi de nouvelles perspectives thérapeutiques / The Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) plays a crucial role during the onset of sepsis by amplifying the host immune response. The TREM-Like Transcript-1 (TLT-1) belongs to the TREM family, is selectively expressed on activated platelets, and is known to facilitate platelet aggregation through binding to fibrinogen. Here we show that a soluble form of TLT-1 is implicated in the regulation of inflammation during sepsis by dampening leukocytes activation and modulating platelet-neutrophil crosstalk. A 17-aa sequence of the TLT-1 extracellular domain (LR17) is responsible for this activity through competition with the TREM-1 ligand. While early or late LR17 treatment of septic mice improves survival, treml-1-/- animals are highly susceptible to polymicrobial infection. The present findings identify platelet derived sTLT-1 as a potent endogenous regulator of sepsis associated inflammation and open new therapeutic perspectives

<div>Applications of electric propulsion to spaceflight in multi-body environments require a targeting algorithm to produce suitable trajectories on the ground and on board spacecraft. The two-level targeter with low thrust (TLT-LT) provides a framework to implement differential corrections in computationally-limited autonomous spacecraft applications as well as the larger design space of pre-mission planning. Extending existing two-level corrections algorithms, applications of the TLT-LT to spacecraft with a range of propulsive capabilities, from nearly-impulsive to low-thrust, are explored. The process of determining partial derivatives is generalized, allowing reduced logical complexity and increased flexibility in designing sequences of thrusting and ballistic segments. Various implementation strategies are explored to enforce constraints on time and other design variables as well as to improve convergence behavior through the use of dynamical systems theory and attenuation factors. The TLT-LT is applied to both nearly-impulsive and low-thrust spacecraft applications in the circular restricted three-body problem to demonstrate the flexibility of the framework to correct trajectories across the spectrum of thrust magnitude. Finally, parameter continuation is employed to extend a family of trajectories from a solution with nearly-impulsive thrust events to the low-thrust regime, and the characteristics of this transition are investigated.</div>