Morphometric Characteristics of the Extreme Eastern Algerian Domestic Donkey (Equus asinus)

The aim of this study was to define the morphometric variability of the extreme Eastern Algerian donkeys. The study was carried out from June to December 2018 in El-Tarf, Souk-Ahras, and Tebessa provinces. The study population involved 65 individuals (32 jacks and 33 jennies) between the ages of 3 and 16 years old. In total, 13 body measurements were used, and 5 zootechnical indexes were calculated. The quantitative and qualitative characteristics were studied in order to establish an ethnic and functional classification of this particular subspecies. The qualitative data demonstrated that the coat colour was variable. Bay and greyish colours were dominant with a respective rate of 61.5 % and 38.5 %, respectively. The head, the nose, as well as the eyes contour colours were mainly grey with 52.3 %, 58.5 % and 50.8 % respectively. The partial absence of the coat particularities was observed. The population presented a significate relationship between the quantitative characters (P < 0.05). The donkeys were longilinear, of a rectilinear profile, compact with massive trends. They had a hyper-metric format. The animals are good for meat production. The General Linear Model (GLM) showed that the body measurements were variable by sex and body mass. The principal component analysis (PCA), the multiple correspondence analyses (MCA) and the ascending hierarchical classification (AHC) revealed that the population was composed of 2 clusters representing 4 animal classes. This study was the first report on the phenotypic characterization of donkeys in the extreme Eastern Algerian area, based on corporal measurements. The results indicated the existence of heterogeneity and suggested the possibilities of genetic improvement within the species

Argumentaire pour une utilisation plus large de la photochimiothérapie extracorporelle chez l’enfant

International audienceThe management of immune diseases in children remains challenging , although significant advances have been made. In addition to pharmacological approaches, extracorporeal photochemotherapy (ECP) is distinctive in its ability to provide immunomodulation without immune suppression or toxicity. However, in practice, this therapy is not widely used because of logistical issues and the lack of robust clinical pediatric studies. Here, we discuss the potential clinical applications of ECP in children and emphasize the need for a rigorous and specifically pediatric clinical evaluation of ECP. ß 2010 Elsevier Masson SAS. All rights reserved. Résumé Malgré l'apport des biothérapies, le traitement des maladies dysim-munitaires sévères et des conflits allogéniques de l'enfant reste difficile et entaché de nombreuses complications. Dans ce contexte, la photo-chimiothérapie extracorporelle (PCE) (thérapie cellulaire qui repose sur l'effet immunomodulateur des cellules mononucléées du patient, prélevées par aphérèse et exposées ex vivo aux rayons ultraviolets A [UVA] en présence de psoralène) a l'avantage notable d'induire une tolérance immunitaire sans générer d'immunosuppression systémique ni de toxicité a ` court, moyen ou long terme. Cette immunomodulation fait intervenir notamment la génération de lymphocytes T régulateurs (T reg). Malgré cela, la PCE est peu utilisée en raison de ses contraintes logistiques et du manque de données cliniques. Nous proposons une revue des indications reconnues et potentielles de la PCE en pédiatrie. Nous insistons sur la nécessité d'une e ´valuation clinique spécifique a ` l'enfant qui ne peut se concevoir sans la participation active des cliniciens pédiatres en particulier dans le domaine de la transplanta-tion et des maladies auto-immunes et inflammatoires

Defective immunogenic cell death of HMGB1-deficient tumors: compensatory therapy with TLR4 agonists

Immunogenic cell death induced by anticancer chemotherapy is characterized by a series of molecular hallmarks that include the exodus of high-mobility group box 1 protein (HMGB1) from dying cells. HMGB1 is a nuclear nonhistone chromatin-binding protein. It is secreted at the late stages of cellular demise and engages Toll-like receptor4 (TLR4) on dendritic cells (DCs) to accelerate the processing of phagocytic cargo in the DC and to facilitate antigen presentation by DC to T cells. The absence of HMGB1 expression by dying tumor cells exposed to anthracyclines or oxaliplatin compromises DC-dependent T-cell priming by tumor-associated antigens. Here, we show that transplantable tumors exhibiting weak expression of nuclear HMGB1 respond to chemotherapy more effectively if the treatment is combined with the local or systemic administration of a highly purified and physiochemically defined and standardized lipopolysaccharide solution, which acts as a high-potency and exclusive TLR4 agonist, called Dendrophilin (DEN). The synergistic antitumor effects mediated by the combination of chemotherapy and immunotherapy relied upon the presence of the MyD88 (myeloid differentiation primary response gene) adapter of TLR4 (but not that of the TIR-domain-containing adapter-inducing interferon-β adapter), in line with the well-characterized action of DEN on the MyD88 signaling pathway. DEN and anthracyclines synergized to induce intratumoral accumulation of interferon-γ-producing CD4+ and CD8+ T lymphocytes. Moreover, DEN could restore the immunogenicity of dying tumor cells from which HMGB1 had been depleted by RNA interference. These findings underscore the potential clinical utility of combination regimens involving immunogenic chemotherapy and certain TLR4 agonists in advanced HMGB1-deficient cancers

Elicitation of potent SARS-CoV-2 neutralizing antibody responses through immunization using a versatile adenovirus-inspired multimerization platform

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has shown that vaccine preparedness is critical to anticipate a fast response to emergent pathogens with high infectivity. To rapidly reach herd immunity, an affordable, easy to store and versatile vaccine platform is thus desirable. We previously designed a non-infectious adenovirus-inspired nanoparticle (ADDomer), and in the present work, we efficiently decorated this original vaccine platform with glycosylated receptor binding domain (RBD) of SARS-CoV-2. Cryo-Electron Microscopy structure revealed that up to 60 copies of this antigenic domain were bound on a single ADDomer particle with the symmetrical arrangements of a dodecahedron. Mouse immunization with the RBD decorated particles showed as early as the first immunization a significant anti-coronavirus humoral response, which was boosted after a second immunization. Neutralization assays with spike pseudo-typed-virus demonstrated the elicitation of strong neutralization titers. Remarkably, the existence of pre-existing immunity against adenoviral-derived particles enhanced the humoral response against SARS-CoV-2. This plug and play vaccine platform revisits the way of using adenovirus to combat emergent pathogens while potentially taking advantage of the adenovirus pre-immunity

Anticancer immunotherapy by CTLA-4 blockade: Obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25

The cytotoxic T lymphocyte antigen-4 (CTLA-4)-blocking antibody ipilimumab induces immune-mediated long-term control of metastatic melanoma in a fraction of patients. Although ipilimumab undoubtedly exerts its therapeutic effects via immunostimulation, thus far clinically useful, immunologically relevant biomarkers that predict treatment efficiency have been elusive. Here, we show that neutralization of IL-2 or blocking the alpha and beta subunits of the IL-2 receptor (CD25 and CD122, respectively) abolished the antitumor effects and the accompanying improvement of the ratio of intratumoral T effector versus regulatory cells (Tregs), which were otherwise induced by CTLA-4 blockade in preclinical mouse models. CTLA-4 blockade led to the reduction of a suppressive CD4(+) T cell subset expressing Lag3, ICOS, IL-10 and Egr2 with a concomitant rise in IL-2-producing effector cells that lost FoxP3 expression and accumulated in regressing tumors. While recombinant IL-2 improved the therapeutic efficacy of CTLA-4 blockade, the decoy IL-2 receptor alpha (IL-2R alpha, sCD25) inhibited the anticancer effects of CTLA-4 blockade. In 262 metastatic melanoma patients receiving ipilimumab, baseline serum concentrations of sCD25 represented an independent indicator of overall survival, with high levels predicting resistance to therapy. Altogether, these results unravel a role for IL-2 and IL-2 receptors in the anticancer activity of CTLA-4 blockade. Importantly, our study provides the first immunologically relevant biomarker, namely elevated serum sCD25, that predicts resistance to CTLA-4 blockade in patients with melanoma