41 research outputs found
PD01 - Respiratory allergens in human milk: potential impact on susceptibility to allergic airway disease
Poster discussion presentationInternational audienc
The challenge of large litters on the immune system of the sow and the piglets
The use of hyperprolific sow lines has increased litter size considerably in the last three decades. Nowadays, in some countries litters can reach up to 18-20 piglets being a major challenge for the sow's physiology during pregnancy, parturition and lactation. The increased number of piglets born per litter prolongs sensibly the duration of farrowing, decreases the piglets' average weight at birth and their vitality, increases the competition for colostrum intake and can affect negatively piglets' survival. This review aims to describe how large litters can affect the immune system of the sow and the piglets and proposes measures to improve this condition.Peer reviewe
Regionalized Development and Maintenance of the Intestinal Adaptive Immune Landscape
The intestinal immune system has the daunting task of protecting us from pathogenic insults while limiting inflammatory responses against the resident commensal microbiota and providing tolerance to food antigens. This role is particularly impressive when one considers the vast mucosal surface and changing landscape that the intestinal immune system must monitor. In this review, we highlight regional differences in the development and composition of the adaptive immune landscape of the intestine and the impact of local intrinsic and environmental factors that shape this process. To conclude, we review the evidence for a critical window of opportunity for early-life exposures that affect immune development and alter disease susceptibility later in life
Impact of beastmilk vitamin A on oral tolerance induction in neonates and allergic diseases prevention
La constante augmentation des allergies en dĂ©but de vie suggĂšre une dĂ©ficience de rĂ©gulation immunitaire au cours de cette pĂ©riode. La tolĂ©rance orale est un mĂ©canisme clĂ© de rĂ©gulation au niveau de lâintestin pour le maintien de lâhomĂ©ostasie immunitaire. Lâobjectif de ma thĂšse a Ă©tĂ© de dĂ©terminer dans un modĂšle murin les mĂ©canismes Ă lâorigine de la tolĂ©rance orale en dĂ©but de vie afin de mieux prĂ©venir le dĂ©veloppement dâallergies. Lâinduction de tolĂ©rance orale en dĂ©but de vie nâest efficace quâĂ partir de la 3Ăšme semaine de vie. Le dĂ©faut de tolĂ©rance orale observĂ© au cours des 2 premiĂšres semaines de vie est la consĂ©quence dâun dĂ©faut de capture de lâantigĂšne et dâexpression de la RALDH (enzyme de conversion du rĂ©tinol en acide rĂ©tinoĂŻque) par les cellules dendritiques CD103+ mĂ©sentĂ©riques, rĂ©sultant en une ignorance de lâantigĂšne. Les taux de rĂ©tinol sanguins en pĂ©riode nĂ©onatale sont trĂšs bas, et un enrichissement du lait maternel en vitamine A permet de corriger cette dĂ©ficience nĂ©onatale ainsi que le dĂ©faut de prĂ©sentation antigĂ©nique des cellules dendritiques CD103+. Cet enrichissement permet Ă©galement de prĂ©venir lâapparition de lâallergie dĂšs les premiers jours de vie. De maniĂšre surprenante, alors que chez la souris adulte, la tolĂ©rance orale dĂ©pend de la gĂ©nĂ©ration de lymphocytes T rĂ©gulateurs, la tolĂ©rance orale observĂ©e chez les souriceaux ĂągĂ©s de 3 semaines et chez les nouveau-nĂ©s ayant reçu de la vitamine A, dĂ©pend de la gĂ©nĂ©ration de lymphocytes Th1.Increased prevalence of allergies in early life suggests a deficiency of immune regulation during this period. Oral tolerance is a key immuno-regulatory mechanism in the gut for immune homeostasis. The principal objective of my thesis was to determine in a murine model the mechanisms at the origin of oral tolerance in early life to better prevent allergy development. We found that induction of oral tolerance in early life is effective only from the 3rd week of life. The defect of oral tolerance observed during the first 2 weeks of life is the consequence of a defect in antigen capture and RALDH expression (enzyme which converts retinol in retinoic acid) by mesenteric CD103+ dendritic cells. Serum levels of retinol in neonatal period are very low, and an enrichment of the maternal milk with vitamin A allows to correct this neonatal deficiency as well as the defect of antigen presentation by the CD103+ dendritic cells. This enrichment also allows allergy prevention from the first days of life. To our surprise, while in adult mice, oral tolerance depends on the generation of regulatory T lymphocytes, oral tolerance observed in the 3 week-old mice and in the newborn which received vitamin A, depends on the generation of Th1 lymphocytes. These results demonstrate that vitamin A levels in early life are directly correlated with Th1 differentiation induced by oral administration of allergen, necessary for allergy prevention. This knowledge should now be taken into account for the implementation of allergy prevention strategies, more specific and better adapted to the neonatal period, such as a supplementation with vitamin A
Impact de la vitamine A du lait maternel sur le développement de la tolérance orale chez le nouveau-né et la prévention des maladies allergiques
Increased prevalence of allergies in early life suggests a deficiency of immune regulation during this period. Oral tolerance is a key immuno-regulatory mechanism in the gut for immune homeostasis. The principal objective of my thesis was to determine in a murine model the mechanisms at the origin of oral tolerance in early life to better prevent allergy development. We found that induction of oral tolerance in early life is effective only from the 3rd week of life. The defect of oral tolerance observed during the first 2 weeks of life is the consequence of a defect in antigen capture and RALDH expression (enzyme which converts retinol in retinoic acid) by mesenteric CD103+ dendritic cells. Serum levels of retinol in neonatal period are very low, and an enrichment of the maternal milk with vitamin A allows to correct this neonatal deficiency as well as the defect of antigen presentation by the CD103+ dendritic cells. This enrichment also allows allergy prevention from the first days of life. To our surprise, while in adult mice, oral tolerance depends on the generation of regulatory T lymphocytes, oral tolerance observed in the 3 week-old mice and in the newborn which received vitamin A, depends on the generation of Th1 lymphocytes. These results demonstrate that vitamin A levels in early life are directly correlated with Th1 differentiation induced by oral administration of allergen, necessary for allergy prevention. This knowledge should now be taken into account for the implementation of allergy prevention strategies, more specific and better adapted to the neonatal period, such as a supplementation with vitamin A.La constante augmentation des allergies en dĂ©but de vie suggĂšre une dĂ©ficience de rĂ©gulation immunitaire au cours de cette pĂ©riode. La tolĂ©rance orale est un mĂ©canisme clĂ© de rĂ©gulation au niveau de lâintestin pour le maintien de lâhomĂ©ostasie immunitaire. Lâobjectif de ma thĂšse a Ă©tĂ© de dĂ©terminer dans un modĂšle murin les mĂ©canismes Ă lâorigine de la tolĂ©rance orale en dĂ©but de vie afin de mieux prĂ©venir le dĂ©veloppement dâallergies. Lâinduction de tolĂ©rance orale en dĂ©but de vie nâest efficace quâĂ partir de la 3Ăšme semaine de vie. Le dĂ©faut de tolĂ©rance orale observĂ© au cours des 2 premiĂšres semaines de vie est la consĂ©quence dâun dĂ©faut de capture de lâantigĂšne et dâexpression de la RALDH (enzyme de conversion du rĂ©tinol en acide rĂ©tinoĂŻque) par les cellules dendritiques CD103+ mĂ©sentĂ©riques, rĂ©sultant en une ignorance de lâantigĂšne. Les taux de rĂ©tinol sanguins en pĂ©riode nĂ©onatale sont trĂšs bas, et un enrichissement du lait maternel en vitamine A permet de corriger cette dĂ©ficience nĂ©onatale ainsi que le dĂ©faut de prĂ©sentation antigĂ©nique des cellules dendritiques CD103+. Cet enrichissement permet Ă©galement de prĂ©venir lâapparition de lâallergie dĂšs les premiers jours de vie. De maniĂšre surprenante, alors que chez la souris adulte, la tolĂ©rance orale dĂ©pend de la gĂ©nĂ©ration de lymphocytes T rĂ©gulateurs, la tolĂ©rance orale observĂ©e chez les souriceaux ĂągĂ©s de 3 semaines et chez les nouveau-nĂ©s ayant reçu de la vitamine A, dĂ©pend de la gĂ©nĂ©ration de lymphocytes Th1
Disparity between vitamin A-induced Th1-dependent oral tolerance in newborn mice and vitamin A-induced atopic sensitization in Guinean girls
Oral tolerance is inefficient in neonatal mice due to a physiological vitamin A deficiency
Increased risk of allergy during early life indicates deficient immune regulation in this period of life. To date, the cause for inefficient neonatal immune regulation has never been elucidated. We aimed to define the ontogeny of oral tolerance and to identify necessary conditions specific for this stage of life. Ovalbumin (OVA) was administered orally to mice through breast milk and efficiency of systemic tolerance to OVA was assessed in adulthood using a model of allergic airway inflammation. Oral tolerance induction was fully efficient starting third week of life. Inefficiency in neonates was a consequence of abnormal antigen transfer across the gut barrier and retinaldehyde dehydrogenase expression by mesenteric lymph node CD103(+) neonatal dendritic cells, resulting in inefficient T-cell activation. Neonates' serum retinol levels were three times lower than in adult mice, and vitamin A supplementation was sufficient to rescue neonatal defects and allow tolerance induction from birth. The establishment of oral tolerance required the differentiation of Th1 lymphocytes in both vitamin A-supplemented neonates and 3-week-old unsupplemented mice. This knowledge should guide the design of interventions for allergy prevention that are adapted to the neonatal stage of life such as vitamin A supplementatio
Breastfeeding is associated with a decreased risk of childhood asthma exacerbations later in life
Background: Breastfeeding has been suggested to influence the risk of asthma and asthma severity in children. However, the conclusions from epidemiologic studies are inconsistent. Methods: We used data from 960 children (aged 4-12 years) using regular asthma medication who participated in the PACMAN study. Breastfeeding exposure was based on questionnaire data and stratified into (i) ever vs never, and (ii) >= 6 vs = 6 months breastfeeding. When we stratified the analysis by family history of asthma, the association between breastfeeding and asthma exacerbations was strong and statistically significant only in children with a positive family history of asthma; adj. OR: 0.34 (95% CI: 0.18-0.66). There was no association between breastfeeding and risk of poor asthma control; adj. OR: 1.04 (95% CI: 0.76-1.41). Conclusion: In a pediatric population with asthma, children who had been breastfed had a statistically significantly lower risk of asthma exacerbations later in life compared to asthmatic children who had not been breastfe