Direct contact of platelets and their released products exert different effects on human dendritic cell maturation

<p>Abstract</p> <p>Background</p> <p>Dendritic cells (DCs) are antigen presenting cells capable of inducing innate and adaptive immune responses. According to the stimulus and their maturation state, DCs induce immunogenic or tolerogenic responses. Platelets (PLTs), which are involved in haemostasis and inflammation, can also interact with DCs. In this study, we examined the effect of PLTs on DC maturation <it>in vitro</it>. Human monocyte-derived DCs were co-cultured for 2 days with homologous PLTs either in the same well or in 0.4 μm-pore size filter-separated compartments.</p> <p>Results</p> <p>Confocal microscopy showed the attachment of PLTs to DC membranes. The DC receptor involved in this interactions was found to be CD162. In addition, we observed that DCs co-cultured with PLTs in filter-separated compartments acquired a mature phenotype (high CD80, CD86, and intermediate CD83 expression; IL-12(p70) production; efficient stimulation of autologous CD4+ T cell proliferation), while DCs co-cultured with PLTs in the same compartment did not undergo phenotypic maturation, did not secrete IL-12(p70) or IL-1β, but instead induced moderate Th2-polarized T cell proliferation.</p> <p>Conclusion</p> <p>These data indicate that (i) PLTs secrete a soluble DC-activating factor that was demonstrated not to be soluble CD40-Ligand (CD154; as could have been expected from <it>in vivo </it>and previous <it>in vitro </it>work) but to be nucleotide, and (ii) that cell-to-cell contact did not induce DC maturation, possibly because nucleotide release by PLTs was prevented by direct contact with DCs. This work demonstrates that PLTs are active elements of the immune system that might play a role in balancing the ability of DCs to polarize T cell responses, therefore making them critical factors in transfusion processes.</p

The Role of Whole Blood Impedance Aggregometry and Its Utilisation in the Diagnosis and Prognosis of Patients with Systemic Inflammatory Response Syndrome and Sepsis in Acute Critical Illness

Objective: To assess the prognostic and diagnostic value of whole blood impedance aggregometry in patients with sepsis and SIRS and to compare with whole blood parameters (platelet count, haemoglobin, haematocrit and white cell count). Methods: We performed an observational, prospective study in the acute setting. Platelet function was determined using whole blood impedance aggregometry (multiplate) on admission to the Emergency Department or Intensive Care Unit and at 6 and 24 hours post admission. Platelet count, haemoglobin, haematocrit and white cell count were also determined. Results: 106 adult patients that met SIRS and sepsis criteria were included. Platelet aggregation was significantly reduced in patients with severe sepsis/septic shock when compared to SIRS/uncomplicated sepsis (ADP: 90.7±37.6 vs 61.4±40.6; p<0.001, Arachadonic Acid 99.9±48.3 vs 66.3±50.2; p = 0.001, Collagen 102.6±33.0 vs 79.1±38.8; p = 0.001; SD ± mean)). Furthermore platelet aggregation was significantly reduced in the 28 day mortality group when compared with the survival group (Arachadonic Acid 58.8±47.7 vs 91.1±50.9; p<0.05, Collagen 36.6±36.6 vs 98.0±35.1; p = 0.001; SD ± mean)). However haemoglobin, haematocrit and platelet count were more effective at distinguishing between subgroups and were equally effective indicators of prognosis. Significant positive correlations were observed between whole blood impedance aggregometry and platelet count (ADP 0.588 p<0.0001, Arachadonic Acid 0.611 p<0.0001, Collagen 0.599 p<0.0001 (Pearson correlation)). Conclusions: Reduced platelet aggregometry responses were not only significantly associated with morbidity and mortality in sepsis and SIRS patients, but also correlated with the different pathological groups. Whole blood aggregometry significantly correlated with platelet count, however, when we adjust for the different groups we investigated, the effect of platelet count appears to be non-significant

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Bryoflore épiphyte des Genévriers thurifères dans les Alpes françaises

An inventory of the corticolous bryophyte flora of incense juniper has been realized in the French Alps, where 25 populations spread over 6 departments have been sampled. The results show a low diversity : 34 species, including 9 of the genus Orthotrichum. Two remarkable species have been identified : Orthotrichum vittii F. Lara, Garilleti & Mazimpaka and Pseudoleskeella tectorum (Funck ex Brid.) Kindb. ex Broth., which appear to be closely related to incense juniper and contribute to the patrimonial value of the alpine juniper forests.Un inventaire de la bryoflore corticole du Genévrier thurifère a été réalisé dans les Alpes françaises. Sur les vingt-cinq populations échantillonnées réparties sur six départements, les résultats montrent une faible diversité spécifique : trente-quatre espèces dont neuf du genre Orthotrichum. Deux espèces remarquables ont été relevées : Orthotrichum vittii F. Lara, Garilleti & Mazimpaka et Pseudoleskeella tectorum (Funck ex Brid.) Kindb. ex Broth. Elles paraissent étroitement liées au Genévrier thurifère et participent à la valeur patrimoniale des thuriféraies alpines.Legland Thomas, Garraud Luc, Hugonnot Vincent. Bryoflore épiphyte des Genévriers thurifères dans les Alpes françaises. In: Ecologia mediterranea, tome 39 n°1, 2013. Actes du IVe Colloque international sur le Genévrier thurifère. 5-8 octobre 2011 Mont-Dauphin et Saint-Crépin (Hautes-Alpes, France) pp. 129-135

Class and subclass selection in parasite-specific antibody responses.

International audienceAntibodies are characteristically induced in many parasitic infection processes. The class and subclass of the antibody response is instrumental because each isotype has a distinct biological function. It is thus crucially important for an infected individual to mount the most appropriate secondary antibody response--that is the response that has the best chance of clearing the infection and/or controlling disease. This represents a fundamental of vaccine strategies. Immuno-epidemiological surveys and in vitro models of antibody production have helped to understand some of the goals which should be achieved when designing antiparasitic vaccines

The enigmatic role of IL-38 in inflammatory diseases

International audienceIL-38 is the most recently discovered cytokine of the IL-1 family and is considered a potential inhibitor of the IL-1 and Toll-like receptor families. IL-38 exerts anti-inflammatory properties, especially on macrophages, by inhibiting secretion of pro-inflammatory cytokines, leading to reduced T-lymphocyte TH17 maturation. IL-38 has been studied most extensively in the context of chronic inflammatory diseases, particularly arthritis, where it is considered an attractive new drug candidate. IL-38 research has entered a new phase, with the realization that IL-38 is important in the pathophysiology of TH17 dependent-diseases (psoriasis, psoriatic arthritis and anky-losing spondylitis). In this review, we provide a critical evaluation of several controversial issues concerning IL-38 function and regulation. There is effectively contrasting data regarding IL-38: it is produced in conditions such as apoptosis, necrosis or inflammation, but data is lacking regarding IL-38 processing and biological function. Furthermore, the receptor for IL-38 has yet to be identified, although three candidate receptors – IL-1R1, IL-36R and IL-1RAPL1–have been proposed. Future studies will hopefully uncover new aspects of this enigmatic cytokine

Jumper’s knee mechanical consequences in professional basketball players: the “Camel’s Back curve”

International audiencePURPOSE:Jumper's knee is characterized by an anterior knee pain during tendon palpation and can be classified in overuse pathologies, secondary to repetitive jumps. The prevalence is high in professional basketball players. It is responsible for an alteration of the motor control inducing a strength deficit of the quadriceps. We aimed to describe an isokinetic curve anomaly, a double-humped curve called "Camel's Back curve", consequence of a jumper's knee history.METHODS:170 Professional basketball players were enrolled (24.8 ± 4.6 years; 91.8 ± 12.0 kg, 194 ± 9.0 cm). All players performed isokinetic tests of the knee extensors on a concentric mode at the angular speed of 60°/s and 180°/s.RESULTS:43 players had a jumper's knee history and 35 (81%) had a "Camel's Back curve" at 60°/s. The sensitivity and the specificity of this curve were 81.3% and 100%, respectively. The minimum torque of strength was decreased from 12 to 18% compared to the 2 maximal peaks. Yet, the strength measured every 5° of ROM was significantly different between the players with "Camel's Back curve" and those with normal curve.CONCLUSIONS:"Camel's Back curve" had never been described in that context. It may be secondary to a protective inhibitory mechanism which could alter jumping. The presence of a "Camel's Back curve" would enable clinicians to adapt physical preparation, knee rehabilitation, and trainings to improve players performances

Platelet toll-like receptors are crucial sensors of infectious danger moieties

In addition to their haemostatic role and function in the repair of damaged vascular epithelium, platelets play a defensive role in innate immunity, having the capacity to produce and secrete various anti-infectious factors, as well as cytokines, chemokines and related products, to interact with other immune cells to modulate immune responses to pathogens. Thus, it is now widely acknowledged that platelets participate in inflammatory processes and infection resolution, most notably by expressing and using receptors to bind infectious pathogen moieties and contributing to pathogen clearance. The ability of platelets to sense external danger signals relates to the expression of certain innate immunity receptors, such as toll-like receptors (TLRs), and the activation of efficient cell signalling machinery. TLR engagement triggers platelet response, which results in adapted degranulation according to: the type of TLR engaged, the nature of the ligand and the milieu; together, the TLR-mediated event and other signalling events may be followed by aggregation. Platelets thus use complex tools to mediate a whole range of functions upon sensing danger. By linking the inflammatory and haemostatic platelet response to infection, TLRs play a central role. The extent of the inflammatory response to pathogen clearance is still a debatable issue and is discussed in this short review

Factors Associated with the Disappearance of Calcifications Following Ultrasound Guided Percutaneous Lavage of Rotator Cuff Calcific Tendinopathy: A Post Hoc Analysis of a Randomized Controlled Trial

International audienc