Saccharomyces boulardii Strain CNCM I-745 Modifies the Mononuclear Phagocytes Response in the Small Intestine of Mice Following Salmonella Typhimurium Infection

Intestinal mononuclear phagocytes (MPs) comprise dendritic cells (DCs) and macrophages (Mφs) that play different roles in response to Salmonella infection. After phagocytosis, DCs expressing CD103 transport Salmonella from the intestinal tract to the mesenteric lymph nodes (MLN) and induce adaptive immune responses whereas resident Mφs expressing CX3CR1 capture bacteria in the lumen and reside in the lamina propria (LP) where they induce a local immune response. CX3CR1+ Mφs are generated from Ly6Chi monocytes that enter the colonic mucosa and differentiate locally. We previously demonstrated that the probiotic yeast Saccharomyces boulardii CNCM I-745 (S.b) prevents infection by Salmonella enterica serovar Typhimurium (ST), decreases ST translocation to the peripheral organs and modifies the pro-and anti-inflammatory cytokine profiles in the gut. In the present study, we investigated the effect of S.b on the migratory CD103+ DCs and the resident CX3CR1+ Mφs. MPs were isolated from the LP of streptomycin-treated mice infected by ST with or without S.b treatment before or during the infection. In S.b-pretreated mice, we observed a decrease of the CD103+ DCs in the LP that was associated with the drop of ST recovery from MLN. Interestingly, S.b induced an infiltration of LP by classical Ly6Chi monocytes, and S.b modified the monocyte-Mφ maturation process in ST-infected mice. Our results showed that S.b treatment induced the expansion of Ly6Chi monocytes in the blood as well as in the bone marrow (BM) of mice, thus contributing to the Mφ replenishment in LP from blood monocytes. In vitro experiments conducted on BM cells confirmed that S.b induced the expansion of CX3CR1+ Mφs and concomitantly ST phagocytosis. Altogether, these data demonstrate that Saccharomyces boulardii CNCM I-745 modulates the innate immune response. Although here, we cannot explicitly delineate direct effects on ST from innate immunity, S. b-amplified innate immunity correlated with partial protection from ST infection. This study shows that S.b can induce the expansion of classical monocytes that are precursors of resident Mφs in the LP

PD01 - Respiratory allergens in human milk: potential impact on susceptibility to allergic airway disease

Poster discussion presentationInternational audienc

Colostrum is required for the postnatal ontogeny of small intestine innate lymphoid type 2 cells and successful anti‐helminth defences

No abstract available

Régulation de l'activité des cellules dendritiques humaines: effets du lipopolysaccharide bactérien et du potentiel redox

Doctorat en sciences médicalesinfo:eu-repo/semantics/nonPublishe

Régulation de l'activité des cellules dendritiques humaines: effets du lipopolysaccharide bactérien et du potentiel redox

Doctorat en sciences médicalesinfo:eu-repo/semantics/nonPublishe

New concepts on the pathogenesis of autoimmune diseases

info:eu-repo/semantics/publishe

Interaction of amiloride with rat parotid muscarinic and alpha-adrenergic receptors.

1. In rat parotid acini, amiloride inhibited the secretion of amylase and the efflux of calcium and rubidium in response to carbamylcholine and to norepinephrine. 2. Amiloride competitively inhibited the binding of [3H]N-methylscopolamine and [3H] is thus a competitive antagonist of muscarinic and norepinephrine alpha-adrenergic receptors. 3. Amiloride did not affect the response to substance P with respect to secretion or ion movements. 4. Thus the Na+/H+ antiporter is not involved in the short-term regulation of amylase secretion and calcium and potassium movements in rat parotid gland function.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Mise en évidence des propriétés immuno-régulatrices des complexes immuns du lait maternel (implications dans la prévention des maladies allergiques)

Au cours de ma thèse, j ai étudié les mécanismes responsables de la tolérance immunitaire observée chez des souris nouveau-nés allaitées par des mères sensibilisées et exposées à un allergène pendant l allaitement. Nous avons montré que ces mères, allergiques, préviennent la survenue d asthme chez les nouveau-nés qu elles allaitent et que cette protection persiste pendant plusieurs semaines après le sevrage. Ce phénomène est associé à un état de tolérance immunitaire causé par le transfert de complexes immuns IgG-antigènes de la mère au nouveau-né à travers la muqueuse intestinale. L induction de tolérance est associée au développement de lymphocytes T régulateurs FoxP3+, dépend de l expression du récepteur Fc néonatal (FcRn) chez le nouveau-né mais ne nécessite pas la présence de TGF-beta ou d IgA dans le lait. Nous avons également montré que les complexes immuns du lait possèdent des propriétés tolérogènes intrinsèques liées à leur structure. Ces propriétés étaient inattendues, les complexes immuns étant classiquement décrits comme activateurs du système immunitaire. Nous avons montré que les complexes immuns du lait étaient constitués d immunoglobulines possédant des résidus d acide sialique à l origine de leurs propriétés immunosuppressives. Ces complexes immuns sialylés sont capables de rendre tolérogènes des cellules présentatrices d antigènes (CPA) en induisant leur sécrétion de TFG-beta, molécule à l origine de l induction des lymphocytes T régulateurs.During my PhD, I studied oral tolerance induced, in a murine model, after breastfeeding by mothers sensitized and exposed to an antigen. We showed that these allergic mothers induce a total and long lasting prevention of asthma to their breastfed newborns. Our results also demonstrated that this prevention is a due to a mechanism of tolerance induction mediated by FoxP3+ regulatory T cells generation in the neonate. Tolerance induction was caused by immunoglobulins G-antigen immune complexes transfer from the mother to the child through the intestinal mucosa and was dependent on the presence of the neonatal Fc receptor (FcRn) expression in the newborn. Moreover, conferred protection did not require the presence of TGF-beta and IgA in mother s milk. Immune complexes present in breast milk of allergic mothers exhibit tolerogenic properties and an intrinsic ability to generate regulatory T cells after interaction with antigen presenting cells (APC). This tolerogenic role of immune complexes was unexpected since they have been described in the literature as immune system activators. Thus, we demonstrated that milk borne immune complexes are composed by immunoglobulins expressing sialic acid residues on their heavy chain which is at the origin of their immunosuppressive properties. Moreover, tolerogenic immune complexes interact with APC and confer them a tolerogenic phenotype characterized by a secretion of TGF-beta. Our study therefore highlights a tolerogenic role of immune complexes. The identification of these immunosuppressive effects could have an impact in medical fields.NICE-BU Sciences (060882101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Régulation de CD1a par CD99 (rôle dans la génération de sous populations de cellules dendritiques humaines)

Les molécules du Complexe Majeur d Histocompatibilité (CMH) jouent un rôle crucial dans la régulation des réponses immunitaires. Il existe trois familles de molécules présentatrices d Ag : les molécules du CMH de classe I et II et les molécules CD1qui possèdent la particularité de présenter des lipides et des glycolipides. Parmi ces molécules, CD1a est exprimée de façon variable à la surface des cellules dendritiques. L objectif de mon travail de thèse a été de déterminer les mécanismes de régulation de l expression de la molécule CD1a sur les cellules dendritiques humaines. Ce travail a donc permis de montrer que la régulation de CD1a par CD99, au sein des cellules dendritiques, implique l activation de la voie de signalisation de p38 MAPK, ainsi que de la voie de l AMPc conduisant à la phosphorylation constitutive des facteurs de transcription ATF-2 et CREB-1. La forme courte de CD99 est, quant à elle, requise pour obtenir une inhibition de la voie de signalisation induite par la forme longue de CD99. La différentiation in vitro de monocytes en cellules dendritiques est caractérisée par un switch de l expression de CD99. Son absence conduit à la génération de cellules dendritiques CD1a négatives. Mon travail a également permis de démontrer l implication des voies de l AMPc et p38 dans la génération de ces deux sous populations de cellules. Cette étude suggère fortement un rôle pour CD99 dans la régulation de la différenciation des monocytes en différents sous types de cellules dendritiques.Introduction: Accumulating data have shown that the microenvironment of dendritic cells modulates subtype differentiation, demonstrating a link between lipoproteins, PPARg activation, and the differentiation and functional activity of CD1- and CD1a+ iDCs. We have previously established that CD99, a ubiquitous surface molecule expressed as two isoforms, could regulate CD1a expression in iDCs. The percentage of CD1a negative iDCs substantially varied among individuals, only 10% of healthy donors exhibit a very low percentage of CD1a positive iDCs. The goal of the present study was to characterize the mechanisms by which exogenous factors confer these effects. Methods: Monocyte from healthy donors or patients with lipid disorders were differentiated into iDCs and CD1a expression was analysed by flow cytometry. CD1a expression was analysed at both membrane and intracellular levels using western blot analysis and flow cytometry in healthy donnors. Then monocytes were differentiated to iDCs under differents conditions so that modify CD1a+/CD1a- cells balance. Results: We demonstrated that lipid disorders in patients shift DC differentiation to the development of CD1a DCs and modulate DC activation through its inhibitory effect on CD1a+ DC differentiation. We suggest that beside activation of intracellular signaling the lipoproteins microenvironement is also crucial for CD1a regulation.NICE-Bibliotheque electronique (060889901) / SudocSudocFranceF