Дисертації з теми "LIE innés"
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Hariss, Fatima. "Etude du rôle des Lymphocytes Intraépithéliaux innés dans la réponse immune protectrice contre Cryptosporidium parvum." Thesis, Université de Lille (2018-2021), 2021. http://www.theses.fr/2021LILUS047.
Intraepithelial lymphocytes (IEL) reside between intestinal epithelial cells and thus are the first immune cells to contact intestinal pathogens. In addition to respond rapidly to infection, they regulate intestinal homeostasis and maintain the epithelial barrier. This wide range of functions is achieved by distinct subsets of T and innate lymphocytes. Innate IEL which share many features with NK/ILC1 cells have been identified recently. These cells dominate the gut epithelium at birth and when the adaptive immunity is compromised. Their role in the immune response against intestinal pathogens remains however poorly studied.During my PhD thesis, I have investigated the role of innate IEL subsets in Crysptosporidium infection. Crysptosporidium is a common parasite that infects the gut epithelium. The infection is self-limiting in immunocompetent individuals, but it can be severe in immunocompromised individuals and children in whom innate IEL dominate.To study the specific role of innate IEL, we have developed an in vitro model that consist to co-culture mice 3D intestinal organoids infected with C parvum with innate IELs from RAG2-/- mice. Thanks to this original model, we demonstrated that innate IELs control parasite proliferation. We further showed that although innate IEL secrete IFN-ƴ in response to C parvum infection, the IFN-ƴ secretion was not sufficient to inhibit parasite proliferation. The protective effect of innate IELs was in fact mediated by a cytotoxic, granzyme-dependent mechanism. Moreover, transcriptomic analysis revealed that infected epithelial cells down regulated serpinb9b, a granzyme inhibitor, and thus may be more sensitive to cytotoxic attack
Chimma, Pattamawan. "Les Monocytes comme lien entre immunité innée et immunité acquise dans le paludisme à Plasmodium falciparum." Paris 7, 2009. http://www.theses.fr/2009PA077085.
Our knowledge of the human blood monocyte (MO), one of the major actors of innate immunity, is still uncomplete, whereas numerous fonctional potentialities and a remarquable plasticity of this cell are associated with a crucial involvement in immune défense against pathogens including malaria. The study of 76 patients presenting with acute uncomplicated malaria showed that activation markers including (HLA-DR, IFN-y, TREM-1) were expressed on circulating CD14+CD16+CD33+ MOs. Co-expression of CCR2 and CX3CR1 on CD14high MOs was associated with the capacity to inhibit parasite growth via an Antibody Dependent Cell Inhibition assay (ADCI). Patients could be defined as belonging to 2 groups differing by parasitaemia at admission. In addition, half of blood MOs expressed CD56, a marker usually found on a minority of MOs from healthy individuals. In healthy malaria-exposed individuals, high percentages of HLA-DR+ mIFN-Y+CD56lowCD33+ MOs were also found on CD14+CD16- cells and these cells displayed a strong phagocytosis activity of infected red blood cells. 10 volunteers experimentally infected by P. Falciparum parasites through successive Anopheles mosquito bites were protected after 3 rounds of infectious bites followed by rapid chloroquine treatment. Increased percentages of CCR2+CX3CR1 + MOs was exclusively detectable in protected volunteers. This resuit was reminiscent of that found in patients with low parasitaemia and high percentages of CCR2+CX3CR1+ MOs and illustrates the contribution of human blood MOs in response to P. Falciparum infection
Simoni, Yannick. "L'immunité innée dans le diabète sucré." Phd thesis, Université René Descartes - Paris V, 2013. http://tel.archives-ouvertes.fr/tel-00944309.
Ittah, Marc. "Lien entre l'immunité innée, la cytokine BAFF (B-cell activating factor of TNF family) et l'auto-immunité." Paris 11, 2009. http://www.theses.fr/2009PA11T037.
Bonneville, Marlene. "Physiopathologie de l'inflammation cutanée : rôle de l'activation de l'immunité innée cutanée dans le développement de l'eczéma allergique de contact." Phd thesis, Université Claude Bernard - Lyon I, 2006. http://tel.archives-ouvertes.fr/tel-00125271.
Dans une première partie, nous montrons que le développement et la sévérité de l'eczéma allergique dépend : i) de l'intensité de l'eczéma irritant lors de la sensibilisation, ii) du recrutement de précurseurs de cellules dendritiques dans la peau, iii) du taux de migration des cellules dendritiques vers les ganglions, iv) de l'activation des lymphocytes T et, v) de leur recrutement dans la peau pendant l'élicitation. La deuxième partie de ce travail porte sur l'étude du rôle du Toll-like receptor-2 (TLR-2), un récepteur de l'immunité innée, dans le développement de l'eczéma allergique. Nous montrons que l'absence du TLR-2 chez des souris sensibilisées conduit à une exacerbation de l'eczéma allergique, suggérant que le TLR-2 est impliqué dans la régulation de la réponse inflammatoire cutanée. L'ensemble de nos travaux démontre une relation directe entre inflammation cutanée et développement d'un eczéma allergique et permet de proposer de nouvelles pistes préventives et thérapeutiques des eczémas basées sur l'utilisation de molécules anti-inflammatoires à usage topique.
Tournadre, Anne. "Immunité innée, balance th1/th17 et précurseurs musculaires dans les myopathies inflammatoires." Phd thesis, Université Claude Bernard - Lyon I, 2010. http://tel.archives-ouvertes.fr/tel-00715926.
Garlatti, Virginie. "Systèmes effecteurs de l'immunité innée : reconnaissance et voies de signalisation." Phd thesis, Université Joseph Fourier (Grenoble), 2008. http://www.theses.fr/2008GRE10073.
The innate immune system triggers inflammatory defences against pathogens or dangerous cells but is also involved in the tolerogenic removal of apoptotic cells. Target recognition is mediated by a wide range of soluble or membrane proteins. Among them are the essential complement recognition proteins: mannose-binding lactin, C1q and ficolins. Whereas the structural recognition properties of mannose-binding lectin BL have been extensively studied, the corresponding properties of ficolins and C1q with their ligands had to be deciphered at the atomic level. This was thus the aim of the first part of the project presented here. This was experimentally studied through the X-ray structural analysis of the corresponding ficolins and C1q recognition domains, alone or in complex with several cognate ligands. We have shown that H- and M- ficolins possess only one binding site, conserved among fibrinogen-like domains. This conserved site does not seem to be active in L-ficolin, but new binding sites were discovered instead, defining a larger surface of recognition more suitable to the binding of elongated polymers. Interestingly, we also found a new binding site for phosphoserine in C1q. We also provided evidence for two unique properties of M-ficolin: the binding of Neu5Ac, a classical self-marker, and a pH-dependent conformational switch of the binding site. As recognition properties of a few recognition proteins do not explain the different behaviour of immune cells with altered-self debris, we initiated a new project to understand signalling pathways in phagocytes during apoptotic cells removal. Many data suggest that a GEF complex: ELMO/DOCK is common to many pathways activated by apoptotic cells recognition and is also a point of regulation. My work in this second project was to initiate the setup of cellular tools to study the behaviour of this complex in different model cell lines. I developed quantitative phagocytic tests and also tools for detection and surexpression of ELMO1 in different cells lines. We also observed the re-localisation of cellular ELMO1 in the phagocytic cup
Potiron, Laurent. "Rôle des phagocytes mononuclées dans la réponse immunitaire innée contre cryptosporidium parvum." Thesis, Tours, 2016. http://www.theses.fr/2016TOUR3809.
Newborns (children, ruminants) are particularly susceptible to intestinal infection by the parasite Cryptosporidium parvum because their immune system is still developing. To date, parasite control methods are limited. There is no vaccine and the only molecule which possess a marketing authorization for calves, Halocur ™, presents toxicity at 2 times the therapeutic dose. The development of new immunoprophylactic methods requires better understanding of the immune mechanisms occurring during infection. Innate immunity plays a major role in controlling the acute phase of infection and we previously demonstrated in the laboratory that intestinal mononuclear phagocytes CD11c+ are key players in the protection process. In this thesis, we confirmed the role of dendritic cells (DC) CD103+ using mice BatF3-/- in which the development of the two DC subsets CD103+CD11b+ and CD103+CD11b- is altered in the intestine making these animals more susceptible to infection. This high susceptibility can be partially mitigated by preventive administration of IL-12 to Batf3-/- neonatal mice. Batf3-/- adult mice which are only deficient for the CD103+CD11b- DC subset were transiently susceptible to infection in contrast to conventional mice that are highly resistant
Riteau, Nicolas. "Immunité innée et inflammasome : rôle des signaux de dangers endogènes." Phd thesis, Université d'Orléans, 2011. http://tel.archives-ouvertes.fr/tel-00684046.
Barassé, Valentine. "Etude de peptides de venin de fourmis : diversité moléculaire et lien avec la fonction immunitaire." Thesis, Toulouse, INPT, 2020. http://www.theses.fr/2020INPT0111.
Animal venoms are natural libraries of bioactive compounds, called toxins, which have been finetuned through the course of evolution. However, numerous venomous organisms are still neglected, especially venomous insects. Several studies of ant venoms revealed that they were peptide-rich. Furthermore, the characterization of the ant Tetramorium bicarinatum venom peptidome revealed that, despite the diversity of mature peptides, they belonged to 3 superfamilies of precursors, some of which have already been described in other aculeate hymenoptera. This study also observed that genes encoding some of them were expressed outside the venom apparatus. These results raise questions about the mechanisms involved in the diversification of peptide toxins from ant venoms, as well as their role apart from the venomous function. To address these issues, the first part of this thesis work consisted in the characterization via proteotranscriptomics approaches of 7 venoms from ants belonging to the different phylogenetic tribes of the Myrmicinae subfamily, and of the venom of one species. belonging to a close subfamily, the Pseudomyrmecinae. A total of 100 peptide toxins with various structures were thus identified and classified into 8 precursor superfamilies. The second part explored the link between peptide toxins of T. bicarinatum venom and its innate immunity via molecular and cellular biology methods. The presence of transcripts encoding certain peptides have been verified in organs which are involved in innate immunity of insects (i.e. fat bodies, digestive tracts). The expression of the genes encoding them has also been evaluated following a bacterial infection. It has thus been shown that the transcripts encoding the selected venom peptides are present in the organs tested, and that some are produced in fat bodies in response to a bacterial infection. These results confirm the existence of a link between the venom peptides and the innate immunity of the ant T. bicarinatum, although further studies are needed
Hamon, Yveline. "Mise en évidence d'une altération fonctionnelle du récepteur soluble de l'immunité innée PTX3 dans la mucoviscidose." Phd thesis, Université d'Angers, 2013. http://tel.archives-ouvertes.fr/tel-00843818.
Benachour, Hamanou. "Peptides antimicrobiens : un lien entre l'immuno-inflammation et les facteurs de risque du syndrome métabolique et des maladies cardiovasculaires." Thesis, Nancy 1, 2010. http://www.theses.fr/2010NAN10012/document.
Multiple risk factors for atherosclerosis and cardiovascular diseases (CVD) act in a synergistic way through inflammatory pathways. Most of CVD risk factors stimulate the release of inflammatory mediators. Defensins and cathelicidins are antimicrobial peptides (AMPs) produced mainly by inflammatory cells. Beside their role in host defense, AMPs are also considered as effectors of inflammatory responses. They have been suggested to play a role in atherosclerosis. To verify this hypothesis, we studied a-defensins DEFA1-3 and cathelicidin LL-37 in a sample of the STANISLAS cohort. We demonstrated that mRNA levels of LL-37 and DEFA1-3 genes in peripheral blood mononuclear cells (PBMCs) of studied subjects are significantly correlated with indicators of obesity, blood pressure, circulating triglycerides and fasting glucose levels, hypo-HDL-C, and leukocytes counts suggesting a role of these genes in CVD. Further analysis revealed that high expression of these genes might be associated with metabolic syndrome. We also showed that expression of LL-37 and DEFA1-3 genes was positively associated with that of FPR receptor gene and that the TT genotype of FPR1 c.32C>T/I11T polymorphism was significantly associated with decreased levels of soluble E-selectin suggesting that these peptides may act through this receptor and such a polymorphism may has an impact on endothelial cells function. In an in vitro model, we found that glucose and insulin modulate the expression of DEFA1-3 and CRAMP cathelicidin genes in human HL-60 neutrophils and mouse 3T3-L1 adipocytes cell lines, respectively. Together, our studies demonstrated that DEFA1-3 and LL-37 could be a potential link between innate immunity and CVD and metabolic syndrome
Mavoungou, Bigouagou Ulrick. "Mise en évidence de l'interaction de la protéine tat du VIH-1 avec les pentraxines humaines : Impact sur la transcription du VIH et la différenciation des cellules dendritiques." Phd thesis, Université d'Angers, 2010. http://tel.archives-ouvertes.fr/tel-00580867.
Thieblemont, Nathalie. "Etude des voies de signalisation TLR/MyD88 en situation normale et immunopathologique." Habilitation à diriger des recherches, Université Pierre et Marie Curie - Paris VI, 2009. http://tel.archives-ouvertes.fr/tel-00424953.
Notre recherche a eu pour objectif d'étudier le rôle des voies de signalisation TLR en situation normale et immunopathologique. Nous avons démontré que : 1) les agonistes des TLR protègent efficacement de l'apparition du diabète spontané chez la souris NOD via l'activation et/ou le recrutement de cellules régulatrices et la production de cytokines immunorégulatrices; 2) Les cellules iNKT sont activées par l'agoniste TLR7 ; 3) La signalisation via TLR7 protège de l'asthme allergique. 4) la voie signalisation via TLR2/MyD88 a un effet majeur sur le développement de l'athérosclérose, ainsi que sur la production de chimiokines et cytokines ; 5) la voie de signalisation MyD88 est impliquée dans le développement et la fonction des lymphocytes iNKT. En conclusion, notre travail met en évidence les propriétés immunomodulatrices des voies de signalisation TLR.
Herbiniere, Juline. "Contribution à la mise en évidence des effecteurs impliqués dans l'immunité innée d'Armadillidium vulgare, crustacé isopode terrestre infecté par une bactérie du genre Wolbachia." Phd thesis, Université de Poitiers, 2005. http://tel.archives-ouvertes.fr/tel-00011699.
Chez les crustacés, les hémocytes sont le siège de l'immunité innée, qui comporte deux types de réponses, une réponse cellulaire et une réponse humorale. La première concerne tous les phénomènes de phagocytose, d'encapsulation et de formation de nodules. La deuxième met en jeu de nombreuses protéines responsables de la mélanisation, de la coagulation et de l'activité antimicrobienne. Ces protéines sont stockées dans les granules des hémocytes et sont libérés dans l'hémolymphe lors d'une infection microbienne.
Chez les isopodes terrestres, aucune étude n'avait été réalisée sur la réponse immunitaire, nous nous sommes donc intéressés aux deux aspects de cette réponse. L'observation en cytologie fine des hémocytes et des organes hématopoïétiques d'A. vulgare infectés ou non par Wolbachia, nous a permis d'une part d'identifier les différents types d'hémocytes et de les comparer à ceux décrits chez les crustacés décapodes et, d'autre part, de suspecter une désorganisation du cytosquelette des cellules infectées par Wolbachia.
La recherche d'activité antimicrobienne a conduit à l'isolement et à la caractérisation d'un peptide antibactérien (armadillidine) produit et stocké dans les hémocytes mais également à mettre en évidence deux peptides (potentiellement antimicrobiens) issus du clivage de l'hémocyanine.
Afin d'identifier les protéines impliquées dans la réponse humorale, une cartographie bidimentionnelle des protéines hémocytaires des deux types d'animaux a été réalisée. L'analyse de ces cartes a permis de mettre en évidence de nombreuses protéines, connues chez les crustacés décapodes et chez d'autres invertébrés, impliquées dans la réponse immunitaire.
Cette étude contribue à la compréhension des mécanismes impliquées dans la réponse immunitaire et devrait permettre d'appréhender la relation d'A. vulgare avec Wolbachia.
Verrier, Eloi. "Bases génétiques de la résistance aux rhabdovirus et réponse cellulaire chez la truite arc-en-ciel : importance des mécanismes de défense innés." Phd thesis, AgroParisTech, 2013. http://pastel.archives-ouvertes.fr/pastel-00914894.
Barblu, Lucie. "Réponse innée des cellules dendritiques plasmacytoides lors de stimulations rétrovirales (HTLV-1, VIH-1)." Phd thesis, Université Paris Sud - Paris XI, 2011. http://tel.archives-ouvertes.fr/tel-00648421.
Raoust, Eloïse. "Rôle des << Toll-Like receptors >> (TLR) et de leurs ligands dans la défense innéé pulmonaire lors d'infections à Pseudomonas aeruginosa." Paris 6, 2009. http://www.theses.fr/2009PA066215.
Bambou, Jean-Christophe. "Etude des interactions entre les cellules épithéliales intestinales et la flore commensale." Paris 6, 2004. http://www.theses.fr/2004PA066360.
Perrot, Ivan. "Interactions cellules NK – Cellules Dendritiques : importance de la coopération entre TLR3 et les Hélicases RLR dans l’initiation d'une réponse innée antivirale." Thesis, Lyon 1, 2009. http://www.theses.fr/2009LYO10146.
Crosstalk between NK cells and DC is critical for the response to the microbial mimic poly(IC) but the dsRNA receptors involved in each cell types remained to be defined. We show herein that two dsRNA, poly(AU) and poly(IC), similarly engaged TLR3 while only poly(IC) triggered the RIG-I and MDA-5 helicases. Both dsRNA triggered NK cell activation within PBMC but only poly(IC) induced IFN-gamma. mDC were required for NK cell activation by the two dsRNA, suggesting that they triggered at least TLR3 on mDC. DsRNA induction of cytolytic potential and IFN-gamma production in NK cells did not require contact with mDC but was dependent on the secretion of type I IFN and IL-12, respectively. Poly(IC) but not poly(AU) synergized with mDC-derived IL-12 for high IFN-gamma production by acting directly on NK cells. Finally, the requirement of TLR3 and the RLR on mDC and the involvement of the RIG-I but not TLR3 on NK cells for the production of IFN-gamma induced by dsRNA was confirmed using TLR3 and Cardif deficient mice and RIG-I specific activator. This cooperation was further confirmed using inactivated FLU virus infected-target cells both in human and mouse system demonstrating that NK cells were able to sense viral material by a direct transfer from infected cells likely through lytic immunological synapse without prior infection of NK cells. Thus, we report for the first time the requirement of cotriggering
Berthet, Julien. "Rôle fonctionnel du Toll-Like Receptor 4 exprimé par les plaquettes sanguines en tant que cellules inflammatoires de l'immunité." Phd thesis, Université Jean Monnet - Saint-Etienne, 2010. http://tel.archives-ouvertes.fr/tel-00673243.
Di, Domizio Jeremy. "Place des cellules dendritiques plasmocytoïdes dans l'immunité innée anti-tumorale : de leur activation par des ligands de TLR à leur fonctionnalité en contexte de mélanome." Phd thesis, Grenoble 1, 2009. http://tel.archives-ouvertes.fr/tel-00439353.
Baeza, Garcia Alvaro. "Rôle de MIF (Macrophage Migration Inhibitory Factor) dans l'immunité innée et la réponse anti-schistosome chez Biomphalaria glabrata." Phd thesis, Université du Droit et de la Santé - Lille II, 2010. http://tel.archives-ouvertes.fr/tel-00665113.
Duffau, Pierre. "Implication de la réponse immunitaire innée dans la physiopathologie des maladies systémiques auto-immunes à travers les exemples du lupus érythémateux systémique et de la polyarthrite rhumatoïde." Thesis, Bordeaux 2, 2011. http://www.theses.fr/2011BOR21901/document.
The aim of the present sudy was to investigate the involvement of the innate immune system in the pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), two models of systemic autoimmune diseases. We show that in SLE patients, platelets are activated by circulating immune complexes. Activated platelet derived CD154 enhances interferon alpha production by immune complex-stimulated dendritic cells in a CD154/CD40 dependent manner. In lupus prone mice, we show that targeting platelet activation improves all measures of disease and overall survival suggesting that this process may provide a new therapeutic target. Proinflammatory cytokines play a central role in the pathogenesis of RA. Gain-of-function polymorphisms in the transcription factor interferon regulatory factor 5 (IRF5) are associated with an increased of developping RA. We now show that IRF5 deficiency substantially reduces disease in a mouse model of RA. As IRF5 participates in TLR signaling, we evaluated TLR requirements in this model and found a significant réduction in disease severity in mice deficient in signaling through the RNA-sensing TLR3 and TLR7. In vitro studies show that TLR3 and TLR7 synergize for proinflammatory cytokine production and that this synergy is markedly diminished in the absence of IRF5. Notably, mice with combined deficiency of TLR3 and TLR7 signaling developed minimal disease indicating an important role for endogenous RNA ligands in disease pathogenesis. Our results bring new elements in the comprehension of the role of innate immunity in the pathogenesis of systemic autoimmune diseases and provide new therapeutic targets
Aillot, Ludovic. "Effets antiviraux de l'agonisation des Toll-like Récepteurs dans les cellules du foie, une nouvelle stratégie immunothérapeutique dans la lutte contre HBV." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSE1139/document.
HBV chronically infects 240 million peoples around the world. HBV chronic infection is a major public health problem and can lead to cirrhosis or/and hepatocarcinoma (HCC). Even if some efficient treatments are already available, based in particular on the use of nucleos(t)ides analogues that induce a decrease of viral load in patients, these drugs do not lead to a definitive HBV cure They enable an important decrease of liver cancer risk but need to be taken life-long. HBV infects hepatocytes the major liver cells which are involve in many vital mechanisms into the organism. The HBV minichromosome, which is formed into infected cells also called cccDNA (i.e., covalently-closed-circular DNA), is not affected by nucleos(t)ides treatments and thus is responsible for HBV persistence. The use of immune receptors (e.g. Toll-like receptors/TLR) agonists can lead to 1) an important cytokines/interferon (IFN) secretion; 2) promote immune cells activation/recruitment and 3) induction of many Interferon-Stimulated Genes (ISG). These mechanisms could lead to a greater viral clearance by cccDNA degradation or silencing. The need for new strategies to permanently eliminate HBV infection led many laboratories, including ours, to explore the use of immunotherapeutic treatments in a context of chronic infection, including innate immune stimulators (e.g. TLR7, TLR8 or RIG-I agonist are under clinical trials). To this end, we got interested on the potential anti-HBV effects of many TLR agonists in liver cells. Our strategy is to stimulate both infected hepatocytes and immune cells. We first characterized the expression of innate immune sensors in primary liver cells as well as in some liver cell lines. This allowed us to: 1) identify which sensors are expressed by liver cells, especially in hepatocytes (TLR2, TLR3, TLR4, TLR5); 2) evaluate their ability to produce cytokines (IL-6, IP-10) upon agonisation; 3) evaluation of cell lines model which are immunologically closed to the primary liver cells. HepaRG and a new liver macrophage cell line call iKC are immunologically close to their primary cells and appear to be relevant models for immune-therapeutics studies. The use of TLR2 and TLR3 agonists on HBV chronically infected hepatocytes showed a strong antiviral effect (i.e., decrease of HBV replication and cccDNA level) mediated directly by NF- kB-inducible and ISG genes activation and indirectly by cytokines secretion. Furthermore, this effect was shown stable over time without any viral replication rebound. This strategy targets not only infected hepatocytes but also immune cells, whose cytokines production also has a strong antiviral effect. Despite a weak in vivo effect in mice, a tuning in agonist doses used and better liver delivery could be an interesting immune-therapeutic strategy. Finally, we were investigated the particular case of TLR9 agonisation in presence of HBV. We showed an interaction between synthetic or not DNA ligands such as CpG ODN and HBV particles. This interaction leads in one hand, to HBV entry inhibition in hepatocytes, on the other hand, to a blockage of ligand delivery to TLR9 in pDC, which is not due to an inhibition of the TLR9 pathway, but to a lack of access of the ligand to its receptor. These two mechanisms are responsible for a decrease of viral infection during its establishment and a decrease in IFN synthesis by pDC, respectively. A decrease in IFN production, which this time was linked to a bona fide inhibition of the TLR9 pathway, in the presence of the sub-viral particles HBsAg was still observed, without retention of TLR9 ligand of the latter. It would seem, therefore, that use of TLR agonists represent an interesting strategy in setting up new anti-HBV immune-therapeutic approaches. However, their improvement will depend on the evaluation of viro-induced inhibitory mechanisms as well as better ways of in vivo delivering these ligands
Ait, Yahia-Sendid Saliha. "Chimiokines et interaction entre l'immunité innée et adaptative dans l'asthme allergique : implication des cellules dendritiques et du récepteur NOD1." Phd thesis, Université du Droit et de la Santé - Lille II, 2012. http://tel.archives-ouvertes.fr/tel-01005122.
Alaoui, Lamine. "Etude de la dynamique de l’axe inhibiteur LILRB2/CMH-I et de sa régulation au cours de l’infection par le VIH/SIV." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS374/document.
Conventional dendritic cells (cDCs) play a crucial role in setting up early immune responses leading to viral control or persistence. In this regard, it has been shown that HIV-1 infection induces cDC dysfunctions characterized by inhibitions in their ability to stimulate T-cells and associated with disease progression. In vitro studies have shown the implication of LILRB2 inhibitory receptor in cDC dysfunctions. However, the dynamic of LILRB2 expression and its role in the early stages of infection are yet to be characterized. In primary HIV-1 infected patients, we observe an increased expression of LILRB2 and its ligands, HLA-I, on the surface of cDCs. Kinetics of LILRB2 and MHC-I expressions during SIV infection of Cynomolgus macaques shows a transient increase in LILRB2 and MHC-I expressions on blood and lymph node cDCs during the first days of infection. We also show that HIV replication, activation of TLR7/8 pathways, and presence of IL-10 and IFN-I drive upregulated expression of LILRB2. Finally, this strong induced LILIRB2 expression seems specific to HIV/SIV infections. Indeed, chikungunya virus infection of cynomolgus macaques, which characterized by a robust antiviral immune response leading to viral control, is associated with decreased expression of LILRB2 on cDCs in the first days of infection. Taken together, our data suggest a major role of the LILRB2/HLA-I inhibitory axis, mediating cDC dysfunctions and thus contributing to inefficient adaptive immune responses and viral persistence
Bouschbacher, Marielle. "MECANISMES DE RECONNAISSANCE DES SIGNAUX DE DANGER PAR LES CELLULES DENDRITIQUES DE LA PEAU ET DES MUQUEUSES : APPLICATION A L'ETUDE DE L'INFECTION PAR LE VIH DANS UN MODELE DE MUQUEUSE VAGINALE HUMAINE INTEGRANT DES CELLULES DE LANGERHANS." Phd thesis, Université Claude Bernard - Lyon I, 2007. http://tel.archives-ouvertes.fr/tel-00285597.
Pham, Van L. "Modulation de la réponse immunitaire par des agonistes de la voie de signalisation TLR/IL-1R dans le modèle d'asthme." Phd thesis, Université René Descartes - Paris V, 2010. http://tel.archives-ouvertes.fr/tel-00514490.
Lim, Hye Kyung. "Inherited TLR3 deficiency in human : genetic etiology of herpes simplex encephalitis and life-threatening influenza in childhood." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066639.
TLR3 is an endosomal receptor for dsRNA, an intermediate of viral replication. Most of the reported human TLR3 deficiency related to life-threatening HSV-1 encephalitis (HSE), in otherwise healthy children. To date, we have described 3 patients with TLR3 deficiency and 7 patients with TLR3 pathway gene deficiency. We herein report the three novel forms of TLR3 deficiency: G743D+R811I and L360P in two patients underlie AD TLR3 deficiency due to dominant negative (DN) and haploinsufficiency, respectively, and R867Q in one patient leads to a partial AR TLR3 deficiency. The patients’ fibroblasts display impaired TLR3 responses and enhanced HSV-1 susceptibility. TLR3 deficiency is therefore a relatively common in childhood HSE, as it is found in six (5%) of the 120 patients studied. In addition, we surprisingly found two TLR3 mutations in two patients with influenza A virus (IAV) pneumonitis. The pathogenesis of isolated severe influenza is largely unknown, until we recently reported a child with AR IRF7 deficiency. Two patients are each heterozygous for P554S and P680L in TLR3. P554S is previously found to be deleterious and DN in HSE patients. P680L is also deleterious and causes AD TLR3 deficiency by haploinsufficiency. We show that P680L heterozygous fibroblasts fail to produce IFN-β and -λ upon poly(I:C) and IAV infection. Furthermore, both P680L heterozygous and AR TLR3-deficient fibroblasts and iPSCs-derived lung epithelium display enhanced susceptibility to IAV, like IRF7-deficient cells. These findings suggest that TLR3 deficiency underlies not only HSE but also severe influenza due to impaired TLR3-dependent, IFN-mediated, CNS or lung-intrinsic antiviral immunity
Laubier, Aurélie. "Caractérisation et implication dans la pathogénicité de deux "Patatin-Like Proteins" de Pseudomonas Aeruginosa, PlpA ET PlpD." Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM4040.
During my PhD, in the PAO1 strain of Pseudomonas aeruginosa, we identified PlpA as a cytotoxin conserved in clinical isolates of various origins, contrary to its virulence factor ExoU homologues. A cytotoxic role of PlpA has been highlighted against phagocytic cells, and showed to depend on the integrity of its Ser/Asp catalytic dyad. An in vivo interactome allowed us to identify mitochondrial transporters as partners of PlpA. Interestingly, PlpA interaction with these partners has an anti-apoptotic effect on macrophages but ultimely allows macrophages death probably by a necroptosis phenomenon. PlpD was previously described by Salacha and collaborators as the SST5d archetype (Salacha et al., 2010). While its exact secretion mechanism remains poorly understood, our work allowed showing that it played a role in bacterial competition. PlpD phylogenetic analysis (Salacha et al., 2010 ; Heinz & Lithgow 2014) revealed its conservation in many species living in hostile environments, suggesting its necessity in the implantation and conservation of ecological niches in the environment or during polymicrobial infections into host organism
Philippe, Lucas. "Le Cluster Mir-17-92, rôle dans la régulation de la réponse inflammatoire au cours de la polyarthrite rhumatoïde." Phd thesis, Université de Strasbourg, 2012. http://tel.archives-ouvertes.fr/tel-00759550.
Sarazin, Aurore. "Les glycannes pariétaux de levures et leur implication dans l'induction et la régulation de la réponse immunitaire de l'hôte." Phd thesis, Université du Droit et de la Santé - Lille II, 2010. http://tel.archives-ouvertes.fr/tel-00493708.
Fornuskova, Alena. "Genes of innate immunity and their significance in evolutionary ecology of free livings rodents." Phd thesis, Université Montpellier II - Sciences et Techniques du Languedoc, 2013. http://tel.archives-ouvertes.fr/tel-01021258.
Israel, Laura. "Un nouveau défaut héréditaire chez l’homme : déficit en TIRAP." Thesis, Paris 5, 2013. http://www.theses.fr/2013PA05T040.
We describe a kindred comprising eight individuals with autosomal recessive complete deficiency of TIRAP (also called MAL), an adaptor downstream of TLR2 and TLR4. The 4-year-old proband suffered at three month of age from a life-threatening pneumonia caused by Staphylococcus aureus. Seven adult relatives, aged between 16 and 50 years, homozygous for the same TIRAP mutation never suffered from any serious infections. The rare missense R121W mutation affects a highly conserved amino acid in the TIR domain of TIRAP. The mutant TIRAP allele is expressed but displays loss of function. Responses to a variety of TLR2 agonists, including PAM2CSK4, PAM3CSK4, and FSL-1, and to the TLR4 agonist lipopolysaccharide (LPS), were impaired in fibroblasts, granulocytes, and monocytes of all TIRAP R121W homozygous individuals tested. Interestingly, the whole blood response to staphylococcal lipoteichoic acid (LTA), another TLR2 agonist, was impaired only in the index case. This defective response was due to a lack of anti-LTA antibodies in the patient’s plasma. The combined effect of the TIRAP R121W mutation and the absence of anti-LTA antibody provide an explanation for severe staphylococcal disease in the index case. These results provide the first description of human inherited TIRAP deficiency and help to delineate the role of human TIRAP in TLR responses. They suggest that human TIRAP-dependent TLR2 immunity is important for the control of S. aureus infection, at least in children lacking anti-LTA antibodies, but that TIRAP is otherwise redundant in host defense
Chignard, Nicolas. "Bile Salts and Nuclear Receptors in Biliary Epithelial Cell Pathophysiology." Habilitation à diriger des recherches, Université Pierre et Marie Curie - Paris VI, 2012. http://tel.archives-ouvertes.fr/tel-00726374.
Sioui, Cassandre. "De l'enchevêtrement des frontières à la précarité identitaire : une étude de la représentation des lieux dans Ourse bleue de Virginia Pésémapéo Bordeleau et Kuessipan de Naomi Fontaine." Mémoire, Université de Sherbrooke, 2014. http://hdl.handle.net/11143/5920.
Mussard, Julie. "Etude fonctionnelle du « Toll-like receptor 9 » et des neutrophiles au cours de l’inflammation : implication dans le développement de la polyarthrite rhumatoïde et d’un modèle expérimental." Thesis, Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCD015/document.
Rheumatoid arthritis (RA) is an autoimmune inflammatory and disabling disease with unknown etiology. Many studies have shown the involvement of adaptative immunity. Especially autoantibodies such as anti-citrullinated protein antibodies (ACPA) are specific for this pathology. However, the role of innate immunity is not much studies, in particular polymorphonuclear neutrophils (PMN) and some molecules, such as TLR9 (Toll-like receptor 9) or C1q. PMN are key cells involved in inflammation and pathogen elimination and can link innate adaptative immunity. All PMN functions are not known. TLR9 recognizes pathogen-derived DNA and even self DNA under certain circumstances. TLR9 might also recognize damage-associated molecular patterns found in RA. C1q is the first component of the classical complement pathway and is activated by immune complexes, potentially containing ACPA. It can also recognize apoptotic cells. The aim of this study was to better understand innate immune mechanisms, sometimes not described, potentially involved in RA. We first demonstrate that PMN express a functional TLR9 at the cell surface, in addition to the normal endosomal expression. They can also produce interferon (IFN)-α described as a plasmacytoid dentritic cell cytokine. Those new PMN functions might participate in inflammatory events found in some autoimmune diseases.We demonstrated that TLR9 is not involved in collagen-induced arthritis model whereas C1q is absolutely required, especially in early steps. Human experiments confirm those results : RA patients do not over-express TLR9 and C1q binding by PMN is correlated with disease activity. All those results offer new insights in the involvement of innate immunity in RA
Chentouh, Ryme. "Caractéristiques de l'activation des monocytes humains par le lipide A monophosphorylé Specific features of human monocytes activation by monophosphoryl lipid A." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCB117.
Lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) agonist is a potent immunomodulator whose use is limited in clinical practice by its toxicity. Monophosphoryl lipid A (MPLA) is a nontoxic derivative of LPS marketed as a vaccine adjuvant and of major interest in many fields. The mechanisms underlying the non-toxicity and immunomodulatory properties of MPLA are poorly characterized in humans. An in vitro model of human monocytes from healthy donors allowed us to define specific characteristics of MPLA activation. MPLA induces a lower production of proinflammatory cytokines (interleukin-1ß-IL-1ß et tumor necrosis factor-TNF) than LPS. The production of anti-inflammatory cytokines such as IL-10 (interleukin-10) and IL-1Ra (IL-1 receptor antagonist) are not significantly different. For a same donor, the respective productions of IL-1ß and TNF after stimulation by LPS or MPLA are not correlated, suggesting an activation of different signaling pathways by each agonist. The use of TLR4 inhibitors (LPS Rhodobacter spheroides and Eritoran) has demonstrated that MPLA and LPS are TLR4 dependent. In contrast, unlike LPS, MPLA does not require the CD14 co-receptor to induce cytokine production. The use of actin polymerization inhibitors (cytochalasin D and latrunculin A) has demonstrated the dependence of MPLA on actin-dependent endocytosis mechanisms for cytokine production. Following LPS stimulation, partial dependence on actin-dependent endocytosis is observed for IL-1ß and TNF production in the high-producers donor subset. This suggests that the signaling pathways initiated by MPLA are intracellular and are also activated in the high-producers donor subset after exposure to LPS. The endosomal signaling pathway of TLR4 is the TRIF-dependent pathway. This signaling pathway is shared by the TLR3. Contrary to what has been published on a mouse model, it has not been possible to show that MPLA signaling is human monocytes is preferentially carried out via the TRIF-dependent pathway. Indeed, unlike poly I:C, a TLR3 agonist, MPLA and LPS do not induce CXCL-10 after stimulation. The fact that the production of CXCL-10 is totally inhibited by cytochalasin D, however, suggests shared mechanisms of endocytosis. SYK-dependent signaling downstream of TLR4 has been implicated in both CD14-dependant TLR4 endocytosis and in high-level productions of proinflammatory cytokines. The use of a SYK phosphorylation inhibitor, R406, revealed no difference between MPLA and LPS. In contrast to the murine model, monocytes produce IL-1ß after a single TLR4 agonist stimulation, demonstrating a one-step inflammasome activation ability. A significant correlation between IL-1ß and TNF production is observed following MPLA exposure. This correlation is not found following LPS exposure. Thus, inflammasome activation could play a key role in MPLA-induced signaling. This is supported by the use of a pan-caspase inhibitor, (Z-VAD) whose inhibitory effect on TNF production is significantly greater for MPLA than for LPS. In conclusion, the non-toxicity of MPLA is reflected in human monocytes by a lower production of IL-1ß and TNF in relation to a signaling different from that initiated by LPS. MPLA requires actin-dependent and CD14-independant TLR4 endocytosis. TLR4 could either initiate intracellular signaling or be a cargo for MPLA which would then directly activate the inflammasome
Biot, Claire. "BCG-THERAPIE ET CANCER DE LA VESSIE : LA CARACTERISATION ET LA MODELISATION DE LA REPONSE IMMUNE AU BCG DANS LA VESSIE REVELENT DES STRATEGIES POUR L'AMELIORATION DE LA REPONSE ANTI-TUMORALE." Phd thesis, Université Pierre et Marie Curie - Paris VI, 2012. http://tel.archives-ouvertes.fr/tel-00827698.
Lantier, Louis. "Les cellules dendritiques CD103+ intestinales : maîtres d'oeuvres du contrôle naturel de la cryptosporidiose et cibles de choix pour l'immunostimulation protectrice contre la maladie." Thesis, Tours, 2013. http://www.theses.fr/2013TOUR4051.
At birth, the neonatal immune system is still developing. In the first part of the thesis we investigated the characteristics of the intestinal immune system of neonates that lead to their greater susceptibility to infection by Cryptosporidium parvum. This protozoan is an excellent model for studying mucosal immune responses. Indeed, its development is restricted to the intestinal epithelium and is strictly related to the immune status of its host which explains the particular susceptibility of neonates and immunocompromised to this zoonotic agent. We have demonstrated that CD103+ dendritic cells (DC) are essential for the control of the acute phase of infection and their low representation in the ileal lamina propria of neonates was responsible for their higher susceptibility to infection. We have accurately identified the CXCR3-dependent mechanism for the recruitment of DC CD1O3+ in the infected mucosa and their ability to produce IL -12 and IFNdz, two major cytokines involved in the mechanism of protection. The second part of this work was to use an immunostimulatory strategy based on administration of TLR ligands that can strongly activate neonatal DC of the intestine. This approach allows a fast and highly effective control of an ongoing C. parvum infection
Raieli, Salvatore. "TLR2 / 1 Orchestrent la réponse de les cellules dendritiques plasmacytoïdes humaines à les bactéries Gram +." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS495/document.
Infections by Gram+ bacteria are worldwide life-threatening diseases where new studies are highlighting the pathological role of Type I interferon (I IFN). Plasmacytoid dendritic cells (pDCs) are the main source of Type I IFN following viral sensing. Recent evidence suggests that human pDCs might sense bacteria. The receptors mediating bacterial sensing in pDCs are not known. During my thesis, I focused on the characterization of pDCs TLR2/1 receptors expression. These two receptors allow pDCs to sense Gram+ bacterial lipoproteins. My work showed that human primary pDCs express TLR1 and TLR2 at the mRNA and protein level. I show that pDCs respond to the Gram+ bacteria M. tuberculosis, S. aureus and L. monocytogenes through TLR2/1 pathway. In human primary pDC, I found that in response to bacterial lipoproteins up-regulation of costimulatory molecules is TLR1-dependent while IFN-I secretion is TLR2-dependent. TLR2 and TLR1 signalling play a different role in the pDCs priming of naïve CD4+ T-cells, inducing proliferation and differentiation to TH1/TH2/Treg subsets. I further demonstrate that these differences rely on the diverse signaling pathway activated by the two TLRs. This work provides the rationale to explore pDCs activity in human bacterial infection
Jacquet, Mickael. "Caractérisation de l'interaction des collagènes de défense avec la calréticuline de Trypanosoma cruzi et CR1/CD35." Phd thesis, Université de Grenoble, 2012. http://tel.archives-ouvertes.fr/tel-01068110.
Petitdemange, Caroline. "Etude des cellules NK au cours des infections par le virus du Chikungunya et le virus de la Dengue." Phd thesis, Université Pierre et Marie Curie - Paris VI, 2014. http://tel.archives-ouvertes.fr/tel-01021134.
Peyret-Lacombe, Alexis. "Etude de l'immuno-réactivité épithéliale gingivale en réponse à deux bactéries commensales : implication du TLR2." Toulouse 3, 2007. http://thesesups.ups-tlse.fr/112/.
Gingival epithelium, exposed to oral microflora, protects underlying tissues in maintaining periodontal homeostasis. To do this, keratinocytes possess Pattern Recognition-Receptors (PRRs) that are able to recognize specifically various bacterial patterns. Communicated cellular informations induce innate immune response, in particular antimicrobial peptides (AMPs) production and inflammation mediators. Our results show that gingival keratinocytes are able to recognize and discriminate true commensal bacteria (S. Sanguinis) or opportunistic bacteria (F. Nucleatum) through a PRR, the Toll-like Receptor 2 in modulating AMP expression, the human ß-defensins 2 and 3 and this of inflammation mediators. This keratinocyte differential activation allow them to provide an adapted response and to maintain periodontal homeostasis
Maksoud, Elie. "Régulations immunitaires dans un modèle Drosophile de la maladie d'Alzheimer." Phd thesis, Université de Strasbourg, 2012. http://tel.archives-ouvertes.fr/tel-00911811.
Grimaldi, David. "Mécanismes cellulaires et moléculaires de l’immunodépression post-infectieuse." Thesis, Paris 5, 2013. http://www.theses.fr/2013PA05T049/document.
Severe sepsis leads to a dysregulated inflammatory response followed by a complex immunosuppressive state that can favor the emergence of nosocomial infections. The cellular and molecular mechanisms that drive the post-infective immunosuppression remain poorly understood. They may involve immune cells that link innate and adaptive immunity such as dendritic cells or innate-like lymphocytes. Furthermore, Toll-like receptors (TLR) are critical determinants of the inflammatory response but their role to the development of sepsis-induced immune dysfunction are unknown. The aim of this research project was to investigate the role of dendritic cells, innatelike T cells and TLR-dependent signalling pathways in the sepsis-induced immunosuppression process. For this purpose, we combined a translational and experimental approach. We assessed dendritic cells blood count in septic patients and showed that the depletion of dendritic cells was associated with the advent of nosocomial infections. We studied 3 populations of innate-like T-cells (γδ lymphocytes, NKT- and MAIT-cells) in septic patients and demonstrated that only the MAIT-cells presented a significant depletion following severe sepsis, the persistence of which was correlated with the advent of nosocomial infection. Last, using knockout mice, we analyzed the relative contribution of TLR2, TLR4 and TLR5 to the host response in a model of late-onset secondary Pseudomonas aeruginosa pneumonia following a sublethal polymicrobial sepsis. We observed that TLR2 deficient mice were specifically protected against the secondary pneumonia through a better bacterial clearance. Our results provide new insights in the pathophysiology of post-infective immunosuppression and suggest potential therapeutic applications
Vigneron, Aurélien. "Dynamique des processus cellulaires et moléculaires dans la symbiose du charançon du genre Sitophilus." Phd thesis, INSA de Lyon, 2012. http://tel.archives-ouvertes.fr/tel-00750638.
Jaffar-Bandjee, Marie-Christine. "Étude de la physiopathologie de l'infection Chikungunya en phase aiguë et chronique chez l'homme." Phd thesis, Université de la Réunion, 2010. http://tel.archives-ouvertes.fr/tel-00671277.
Engel, Elodie. "Identification des "Ubiquitin Specific proteases" impliquées dans la régulation des voies de l'immunité chez la drosophile." Phd thesis, Université Joseph Fourier (Grenoble), 2009. http://tel.archives-ouvertes.fr/tel-00403268.