Mesenteric lymph node cells from neonates present a prominent IL-12 response to CpG oligodeoxynucleotide via an IL-15 feedback loop of amplification

At birth, the immune system is still in development making neonates more susceptible to infections. The recognition of microbial ligands is a key step in the initiation of immune responses. It can be mimicked to stimulate the immune system by the use of synthetic ligands recognising pattern recognition receptors. In human and mouse, it has been found that neonatal cytokine responses to toll-like receptor (TLR) ligands differ in many ways from those of adults but the relevant studies have been limited to cord blood and spleen cells. In this study, we compared the responses in neonate and adult sheep to CpG oligodeoxynucleotides (ODN), a TLR9 ligand, in both a mucosal and a systemic organ. We observed that in response to CpG-ODN more IL-12 was produced by neonatal than adult sheep cells from mesenteric lymph nodes (MLN) and spleen. This higher IL-12 response was limited to the first 20 days after birth for MLN cells but persisted for a longer period for spleen cells. The major IL-12-producing cells were identified as CD14+CD11b+. These cells were poor producers of IL-12 in response to direct stimulation with CpG-ODN and required the cooperation of other MLN cells. The difference in response to CpG-ODN between neonates and adults can be attributed to both a higher proportion of CD14+CD11b+ cells in neonate lambs and their higher capacity to produce IL-15. The IL-15 increases IL-12 production by an amplifying feedback loop involving CD40

Plasma membrane proteomes of differentially matured dendritic cells identified by LC-MS/MS combined with iTRAQ labelling

AbstractDendritic cells (DCs) play a pivotal role in polarising Th lymphocyte subsets but it is unclear what molecular events occur when DCs generate Th2-type responses. Here, we analysed plasma membrane-enriched fractions from immature, pro-Th1 and pro-Th2 DCs and used a combination of iTRAQ labelling and LC–MS/MS to quantify changes in the proteomes. Analysis was performed on triplicate biological samples and changes verified by flow cytometry. MHC class II molecules and CD29 were up-regulated in pro-Th1 DCs whilst CD18 and CD44 were up-regulated in pro-Th2 DCs. One of the most down-regulated molecules in pro-Th1 DCs was YM-1 whilst the greatest decrease in pro-Th2 DCs was NAP-22. Other molecules up-regulated in pro-Th2 DC compared to pro-Th1 DCs included some potentially involved in protein folding during antigen processing (clathrin and Rab-7), whilst other non-membrane proteins such as enzymes/transporters related to cell metabolism (malate dehydrogenase, pyruvate kinase, and ATPase Na+/K+) were also recorded. This suggests that pro-Th2 DCs are more metabolically active while pro-Th1 DCs have a mature ‘end state’. Overall, although several molecules were preferentially expressed on pro-Th2 DCs, our proteomics data support the view of a ‘limited maturation’ of pro-Th2 DCs compared to pro-Th1 DCs

Cellular and Molecular Mechanisms Underlying the Strong Neonatal IL-12 Response of Lamb Mesenteric Lymph Node Cells to R-848

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Maternal Supplementation of Food Ingredient (Prebiotic) or Food Contaminant (Mycotoxin) Influences Mucosal Immune System in Piglets

The early life period is crucial for the maturation of the intestinal barrier, its immune system, and a life-long beneficial host–microbiota interaction. The study aims to assess the impact of a beneficial dietary (short-chain fructooligosaccharides, scFOS) supplementation vs. a detrimental dietary environment (such as mycotoxin deoxynivalenol, DON) on offspring intestinal immune system developmental profiles. Sows were given scFOS-supplemented or DON-contaminated diets during the last 4 weeks of gestation, whereas force-feeding piglets with DON was performed during the first week of offspring life. Intestinal antigen-presenting cell (APC) subset frequency was analyzed by flow cytometry in the Peyer’s patches and in lamina propria and the responsiveness of intestinal explants to toll-like receptor (TLR) ligands was performed using ELISA and qRT-PCR from post-natal day (PND) 10 until PND90. Perinatal exposure with scFOS did not affect the ontogenesis of APC. While it early induced inflammatory responses in piglets, scFOS further promoted the T regulatory response after TLR activation. Sow and piglet DON contamination decreased CD16+ MHCII+ APC at PND10 in lamina propria associated with IFNγ inflammation and impairment of Treg response. Our study demonstrated that maternal prebiotic supplementation and mycotoxin contamination can modulate the mucosal immune system responsiveness of offspring through different pathways

Différenciation de progéniteurs hématopoïétiques murins en macrophages suppresseurs fonctionnels

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Rôle des cellules myéloïdes dans la pathogénie du diabète de type 1 (mise en évidence d'un déficit de différenciation, de maturation et de fonction des macrophages inhibiteurs chez la souris Non Obese Diabetic)

Les macrophages inhibiteurs (iMacs), mobilisés lors d'une réponse immunitaire intense, exercent une action suppressive via la sécrétion de NO et des contacts cellulaires avec les lymphocytes T activés. Ces cellules pourraient limiter l'expansion des lymphocytes T autoréactifs et participer ainsi au contrôle du développement des maladies autoimmunes. L'objectif de notre étude a été de caractériser le phénotype et la fonction des iMacs dans un modèle privilégié de diabète autoimmun, la souris NOD (non obese diabetic) comparativement aux souris BALB/c. Après avoir précisé l'origine, jusqu'alors peu connue, des iMacs à partir de progéniteurs hématopoïétiques, nous avons montré un défaut de différenciation et de maturation de ces cellules chez la souris NOD. Enfin, suite à un traitement immunosuppresseur au cyclophosphamide, connu pour induire un recrutement des iMacs au sein de la rate, nous avons observé une déficience de différenciation et de fonction de ces cellules chez la souris NOD.Inhibitory macrophages (iMacs), recruited during intense immune responses, exert immunosuppressive functions via a NO secretion and cellular interactions with activated T lymphocytes. These cells could limit expansion of autoreactive T cells and may thus participate to the control of autoimmune disease development. The aim of our study was to characterize iMacs phenotype and function in a privileged model of autoimmune diabetes, the non obese diabetic (NOD) mouse comparatively to the BALB/c mouse. As the origin of iMacs was poorly known, we showed firstly their differentiation from hematopoietic progenitor cells. Secondly, we described that iMacs could not differentiate and mature in vitro efficiently from hematopoietic progenitors of NOD mouse. Finally, following an immunosuppressive treatment with cyclophosphamide, known to induce iMacs recruitment in spleen of BALB/c mice, we observed deficiencies of NOD mouse iMacs differentiation and function.NANTES-BU Sciences (441092104) / SudocSudocFranceF

Proteomic study of dendritic cell phenotype matured in response to products released by schistosome larvae

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Development of gut and gut-associated lymphoid tissues in piglets: role of maternal environment

Development of gut and gut-associated lymphoid tissues in piglets: role of maternal environmen

Development of the intestinal immune system in young pigs – role of the microbial environment

International audienceThe intestinal immune system of the neonatal piglet acquires structural and functional competences during the first months of postnatal life. Passive, innate and adaptive immune systems confer appropriate protection from harmful pathogens along with tolerance to ubiquitous dietary antigens and microbiota. The intestinal immune and non-immune barrier as well as microbiota co-develop postnatally. The timing of the developmental pattern of these actors that participate in establishing a homeostatic state in suckling and weaned piglets is described in the current chapter. It is also widely known that maternal diet composition influences colostrum and milk composition, leading to changes in passive immunity transferred to the neonates. Moreover, maternal environment that induces changes in the microbiota of the dam also has huge effects on the gut immune system profile of the offspring. Changes in gut bacterial colonization that are caused by supplementation of gestating and lactating sow diets with prebiotics and by maternal antibiotic treatment, are detailed in relation with their impact on offspring intestinal immune system development and sensitivity to inflammatory challenges. Finally, the long-term impacts of early modifications of offspring gut bacterial colonization are presented to illustrate microbiota-related imprinting of intestinal physiology

Déficience des iMacs chez la souris NOD : implication dans le diabète autoimmun ?

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