4 research outputs found
Alternatives to in-feed antibiotics in pigs: Evaluation of probiotics, zinc or organic acids as protective agents for the intestinal mucosa. A comparison of in vitro and in vivo results
Weaned pigs are susceptible to frequent infectious diseases. Antibiotics have been used over decades to reduce pathogen infections, but many microorganisms are becoming resistant to antibiotics. Thus, there is an urgent need to find alternatives to in-feed antibiotics. Up to now, various compounds have been used as alternatives, giving promising but sometimes contrasting results. In recent years, the in vitro models of cell culture have been proposed for the screening of various compounds and understanding their mechanisms of action. The intestine is a complex system with a continuous cross-talk among epithelial cells, the local immune system and microflora. Alternatives to in-feed antibiotics may interact with any of these constituents. This review presents data on the protective effects of probiotics, zinc salts and organic acids, used as alternatives to in-feed antibiotics, against pathogen induced damage and inflammatory processes in the intestinal cells and the underlying mechanisms, with an attempt to compare in vitro and in vivo results. All the alternatives tested resulted in effective protection against pathogens by a series of interactions with intestinal cells and pathogens, including the inhibition of adhesion and invasion of pathogens, interference in signalling pathways induced by pathogenic bacteria, maintenance of the epithelial cell cytoskeleton and junctional structure and modulation of the host immune response.Alternatives aux antibiotiques additifs alimentaires chez le porc : évaluation des probiotiques, sels de zinc ou acides organiques comme agents protecteurs de la muqueuse intestinale. Comparaison des résultats in vitro avec les observations in vivo. Le porcelet est sensible aux infections gastro-intestinales au moment du sevrage. Les antibiotiques additifs alimentaires ont été utilisés pendant des décennies pour réduire ces infections, mais de nombreux microorganismes sont devenus résistants à ces substances. Aussi, est-il urgent de trouver des alternatives aux antibiotiques additifs alimentaires. Jusqu’à présent, diverses alternatives ont été envisagées, certaines donnant des résultats prometteurs, d’autres des résultats variables. Au cours des dernières années, les modèles in vitro de cultures cellulaires ont été proposés pour cribler ces substances et élucider leurs mécanismes d’action. L’intestin est un système complexe faisant intervenir des communications permanentes entre les cellules épithéliales, le système immunitaire local et la microflore. Les alternatives aux antibiotiques peuvent interagir avec n’importe lequel de ces composants. Le présent article fait la synthèse des effets protecteurs et des mécanismes d’action des probiotiques, des sels de zinc et des acides organiques, utilisés comme alternatives aux antibiotiques dans les processus inflammatoires et les altérations cellulaires épithéliales in vitro, induites par des agents pathogènes. Elle tente de comparer ces résultats avec les observations in vivo. Toutes les alternatives évaluées ont été efficaces contre les agents pathogènes, via des mécanismes d’interaction cellules épithéliales-agents pathogènes. Ces mécanismes incluaient l’inhibition de l’adhésion et de l’invasion cellulaire par ces pathogènes, la modulation des mécanismes de signalisation intracellulaire induits par les bactéries pathogènes, le maintien de la structure du cytosquelette et des jonctions serrées des cellules épithéliales, et enfin la modulation des réponses immunitaires de la cellule hôte
Novel Approach for Food Safety Evaluation. Results of a Pilot Experiment To Evaluate Organic and Conventional Foods
A Novel Bispecific T-Cell Engager (CD1a x CD3ε) BTCE Is Effective against Cortical-Derived T Cell Acute Lymphoblastic Leukemia (T-ALL) Cells
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy burdened by poor prognosis. While huge progress of immunotherapy has recently improved the outcome of B-cell malignancies, the lack of tumor-restricted T-cell antigens still hampers its progress in T-ALL. Therefore, innovative immunotherapeutic agents are eagerly awaited. To this end, we generated a novel asymmetric (2 + 1) bispecific T-cell engager (BTCE) targeting CD1a and CD3ε (CD1a x CD3ε) starting from the development of a novel mAb named UMG2. UMG2 mAb reacts against CD1a, a glycoprotein highly expressed by cortical T-ALL cells. Importantly, no UMG2 binding was found on normal T-cells. CD1a x CD3ε induced high T-cell mediated cytotoxicity against CD1a+ T-ALL cells in vitro, as demonstrated by the concentration-dependent increase of T-cell proliferation, degranulation, induction of cell surface activation markers, and secretion of pro-inflammatory cytokines. Most importantly, in a PBMC-reconstituted NGS mouse model bearing human T-ALL, CD1a x CD3ε significantly inhibited the growth of human T-ALL xenografts, translating into a significant survival advantage of treated animals. In conclusion, CD1a x CD3ε is a novel BTCE highly active against CD1a-expressing cortical-derived T-ALL cells suitable for clinical development as an effective therapeutic option for this rare and aggressive disease