TREM-1, nouvel acteur de la cellule endothéliale et de la plaquette

TREM-1 (Triggering Receptor Expressed on Myeloid cells-1) is an immunoreceptor known to be expressed by neutrophils and monocytes/macrophages. It plays a fundamental role in the amplification of the inflammatory response mediated by TLR (Toll-like receptor) engagement. Using several experimental tools, we show for the first time that TREM-1 is expressed by two other cell types: endothelial cells and platelets. The selective deletion of TREM-1 at the endothelial level protects against septic shock by reducing dysfunction and vascular inflammation, modulating the recruitment and the activation of inflammatory cells, and improves survival. In addition, pharmacological modulation via the use of the LR12 peptide or genetic invalidation of TREM-1 alters platelet activation and prevents the formation of thrombi. These results provide new insights on the TREM-1 biology and may explain the protective effect of the TREM-1 modulation during acute inflammatory diseases such as septic shock beyond its role on myeloid cells. In addition, TREM-1 modulating agents such as LR12 could potentially be useful additions in antiplatelet therapies for thrombotic disordersTREM-1 (Triggering Receptor Expressed on Myeloid cells-1) est un immunorécepteur connu pour être exprimé par les neutrophiles et les monocytes/macrophages. Il joue un rôle fondamental dans l’amplification de la réponse inflammatoire via les TLR (Toll-like receptor). A l’aide de plusieurs outils expérimentaux, nous montrons pour la première fois que TREM-1 est exprimé par deux nouveaux types cellulaires : la cellule endothéliale et les plaquettes. La délétion sélective de TREM-1 au niveau endothélial protège du choc septique en réduisant la dysfonction et l’inflammation vasculaire, en modulant le recrutement et l’activation des cellules inflammatoires, et en améliorant la survie. De plus, la modulation pharmacologique via l’utilisation du peptide LR12 ou l'invalidation génétique de TREM-1 altère l'activation plaquettaire et prévient la formation de thrombus. Ces résultats fournissent un nouvel aperçu de la biologie TREM-1 et peuvent expliquer l'action protectrice de la modulation TREM-1 au cours des maladies inflammatoires aiguës comme le choc septique, au-delà de leurs effets sur les cellules myéloïdes. De plus, les agents modulateurs de TREM-1 tels que LR12 pourraient potentiellement être des ajouts utiles dans les thérapies antiplaquettaires dans le cadre de troubles thrombotique

TREM-1, a new player in endothelial cells and platelets

TREM-1 (Triggering Receptor Expressed on Myeloid cells-1) est un immunorécepteur connu pour être exprimé par les neutrophiles et les monocytes/macrophages. Il joue un rôle fondamental dans l’amplification de la réponse inflammatoire via les TLR (Toll-like receptor). A l’aide de plusieurs outils expérimentaux, nous montrons pour la première fois que TREM-1 est exprimé par deux nouveaux types cellulaires : la cellule endothéliale et les plaquettes. La délétion sélective de TREM-1 au niveau endothélial protège du choc septique en réduisant la dysfonction et l’inflammation vasculaire, en modulant le recrutement et l’activation des cellules inflammatoires, et en améliorant la survie. De plus, la modulation pharmacologique via l’utilisation du peptide LR12 ou l'invalidation génétique de TREM-1 altère l'activation plaquettaire et prévient la formation de thrombus. Ces résultats fournissent un nouvel aperçu de la biologie TREM-1 et peuvent expliquer l'action protectrice de la modulation TREM-1 au cours des maladies inflammatoires aiguës comme le choc septique, au-delà de leurs effets sur les cellules myéloïdes. De plus, les agents modulateurs de TREM-1 tels que LR12 pourraient potentiellement être des ajouts utiles dans les thérapies antiplaquettaires dans le cadre de troubles thrombotiquesTREM-1 (Triggering Receptor Expressed on Myeloid cells-1) is an immunoreceptor known to be expressed by neutrophils and monocytes/macrophages. It plays a fundamental role in the amplification of the inflammatory response mediated by TLR (Toll-like receptor) engagement. Using several experimental tools, we show for the first time that TREM-1 is expressed by two other cell types: endothelial cells and platelets. The selective deletion of TREM-1 at the endothelial level protects against septic shock by reducing dysfunction and vascular inflammation, modulating the recruitment and the activation of inflammatory cells, and improves survival. In addition, pharmacological modulation via the use of the LR12 peptide or genetic invalidation of TREM-1 alters platelet activation and prevents the formation of thrombi. These results provide new insights on the TREM-1 biology and may explain the protective effect of the TREM-1 modulation during acute inflammatory diseases such as septic shock beyond its role on myeloid cells. In addition, TREM-1 modulating agents such as LR12 could potentially be useful additions in antiplatelet therapies for thrombotic disorder

Comparaison de modèles numériques de surface photogrammétriques de différentes résolutions en forêt mixte. Estimation d'une variable dendrométrique simple : la hauteur dominante

International audienceRenewed interest in photogrammetry and recent developments of unmanned aerial vehicles (UAVs) open newpossibilities in the field of forest planning and management.As the assessment of forest dendrometric parameters is usually a costly task, involving intensive field measurements, wewere interested to evaluate how the use of accurate photogrammetric digital surface models (DSMs) could facilitatethese estimations. Based on DSMs, dendrometric models were calibrated using circular plots (700 m²) measured in anarea of interest (AOI). UAVs flight above these AOI were acquired at very high resolution (VHRI) giving images with aspatial resolution of 2.5 cm, as compared to 25,0 cm for the standard IGN aerial images.We were also interested in assessing the impact of DSMs resolution. For this purpose, DSMs were computed at theoriginal resolution as well as degraded resolutions from 5.0 cm to 40.0 cm. Each DSM's elevation was then compared tomanual stereoscopic measurements realized on the VHRI.By subtracting a digital terrain model (DTM) from each DSM, we derived canopy height models (CHMs). From theseCHMs, we observed that plot height distributions were interesting indicators of forest structures and we were also able toestablished dominant height (H0) models. These results underline the interest of new photogrammetric approaches, andthe importance of spatial resolutions, to improve forest planning and management

Les sépultures de Saint-Pierre d'Engollon

L'église d'Engollon a servi pendant plusieurs siècles de lieu d'inhumation pour une partie des habitants de la région. Les travaux d'assainissement de l'édifice nécessitant le creusement de l'ensemble du sous-sol, pas moins de 147 sépultures ont été mises au jour sous la nef et le chœur, ainsi que sur le pourtour de l'édifice actuel. Ces anciennes sépultures ont été soigneusement dégagées, décrites et étudiées avant que les squelettes ne soient déposés. Deux groupes de sépultures particulièrement importantes font ici l'objet d'une brève présentation: les sépultures du Haut Moyen Age et quelques tombes dans le chœur gothique

Persistently Elevated Soluble Triggering Receptor Expressed on Myeloid Cells 1 and Decreased Monocyte Human Leucocyte Antigen DR Expression Are Associated With Nosocomial Infections in Septic Shock Patients

International audienceSepsis-acquired immunosuppression may play a major role in patients' prognosis through increased risk of secondary infections. Triggering receptor expressed on myeloid cells 1 (TREM-1) is an innate immune receptor involved in cellular activation. Its soluble form (sTREM-1) has been described as a robust marker of mortality in sepsis. The objective of this study was to evaluate its association with the occurrence of nosocomial infections alone or in combination with human leucocyte antigen-DR on monocytes (mHLA-DR). DESIGN: Observational study. SETTING: University Hospital in France. PATIENTS: One hundred sixteen adult septic shock patients as a post hoc study from the IMMUNOSEPSIS cohort (NCT04067674). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma sTREM-1 and monocyte HLA-DR were measured at day 1 or 2 (D1/D2), D3/D4, and D6/D8 after admission. Associations with nosocomial infection were evaluated through multivariable analyses. At D6/D8, both markers were combined, and association with increased risk of nosocomial infection was evaluated in the subgroup of patients with most deregulated markers in a multivariable analysis with death as a competing risk. Significantly decreased mHLA-DR at D6/D8 and increased sTREM-1 concentrations were measured at all time points in nonsurvivors compared with survivors. Decreased mHLA-DR at D6/D8 was significantly associated with increased risk of secondary infections after adjustment for clinical parameters with a subdistribution hazard ratio of 3.61 (95% CI, 1.39-9.34; p = 0.008). At D6/D8, patients with persistently high sTREM-1 and decreased mHLA-DR presented with a significantly increased risk of infection (60%) compared with other patients (15.7%). This association remained significant in the multivariable model (subdistribution hazard ratio [95% CI], 4.65 [1.98-10.9]; p < 0.001). CONCLUSIONS: In addition to its prognostic interest on mortality, sTREM-1, when combined with mHLA-DR, may help to better identify immunosuppressed patients at risk of nosocomial infections