Pulsed vertical jet in cross flow at mean blowing ratios 0.35 and 0.45

This thesis deals with a pulsed vertical jet transverse to a cross flow (U∞=1.6m/s) at mean blowing ratios 0.35 and 0.45. First the reasons of this study are explained and the previous work in the field is described. Then the experimental setup, the experimental procedures and the data processing are detailed. The system (wind tunnel and jet) is characterized before studying the Jet in Cross Flow (JICF). The JICF is explored under unforced and forced conditions through LASER sheet visualizations and constant temperature anemometry (CTA) measurements using hot-wire sensors. Blowing ratios ranging from 0.150 to 0.600 are studied for the unforced JICF to cover the range of blowing ratios present in the forced cases. Mean blowing ratios of 0.35 and 0.45 were studied at various low and peak-to-peak blowing ratio conditions, duty cycles of 0.25, 0.50 and 0.70, and forcing frequencies of 0.5Hz, 1.0Hz, 5.0Hz and 10.0Hz. Associated physical phenomena and the influence of the various parameters are discussed

Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid

To maintain immune homeostasis, the intestinal immune system has evolved redundant regulatory strategies. In this regard, the gut is home to a large number of regulatory T (T reg) cells, including the Foxp3+ T reg cell. Therefore, we hypothesized that the gut environment preferentially supports extrathymic T reg cell development. We show that peripheral conversion of CD4+ T cells to T reg cells occurs primarily in gut-associated lymphoid tissue (GALT) after oral exposure to antigen and in a lymphopenic environment. Dendritic cells (DCs) purified from the lamina propria (Lp; LpDCs) of the small intestine were found to promote a high level of T reg cell conversion relative to lymphoid organ–derived DCs. This enhanced conversion by LpDCs was dependent on TGF-β and retinoic acid (RA), which is a vitamin A metabolite highly expressed in GALT. Together, these data demonstrate that the intestinal immune system has evolved a self-contained strategy to promote T reg cell neoconversion

Modulation of host responses by oral commensal bacteria.

Immunomodulatory commensal bacteria are proposed to be essential for maintaining healthy tissues, having multiple roles including priming immune responses to ensure rapid and efficient defences against pathogens. The default state of oral tissues, like the gut, is one of inflammation which may be balanced by regulatory mechanisms and the activities of anti-inflammatory resident bacteria that modulate Toll-like receptor (TLR) signalling or NF-κB activation, or influence the development and activities of immune cells. However, the widespread ability of normal resident organisms to suppress inflammation could impose an unsustainable burden on the immune system and compromise responses to pathogens. Immunosuppressive resident bacteria have been isolated from the mouth and, for example, may constitute 30% of the resident streptococci in plaque or on the tongue. Their roles in oral health and dysbiosis remain to be determined. A wide range of bacterial components and/or products can mediate immunomodulatory activity, raising the possibility of development of alternative strategies for therapy and health promotion using probiotics, prebiotics, or commensal-derived immunomodulatory molecules

Bovine milk derived skimmed milk powder and whey protein concentrate modulates Citrobacter rodentium shedding in the mouse intestinal tract

Skimmed milk powder (SMP) and whey protein concentrate (WPC) were manufactured from fresh milk collected from cows producing high or low Immunoglobulin (Ig) A levels in their milk. In addition commercial products were purchased for use as diluent or control treatments. A murine enteric disease model (Citrobacter rodentium) was used to assess whether delivery of selected bioactive molecules (IgA, IgG, Lactoferrin (Lf)) or formulation delivery matrix (SMP, WPC) affected faecal shedding of bacteria in C. rodentium infected mice. In trial one, faecal pellets collected from mice fed SMP containing IgA (0.007–0.35 mg/mL), IgG (0.28–0.58 mg/mL) and Lf (0.03–0.1 mg/mL) contained fewer C. rodentium (cfu) compared to control mice fed water (day 8, p < 0.04, analysis of variance (ANOVA) followed by Fisher’s unprotected least significant difference (ULSD)). In trial two, WPC containing IgA (0.35–1.66 mg/mL), IgG (0.58–2.36 mg/mL) and Lf (0.02–0.45 mg/mL) did not affect C. rodentium shedding, but SMP again reduced faecal C. rodentium levels (day 12, p < 0.04, ANOVA followed by Fisher’s ULSD). No C. rodentium was detected in sham phosphate-buffered saline inoculated mice. Mice fed a commercial WPC shed significantly greater numbers of C. rodentium over 4 consecutive days (Fishers ULSD test), compared to control mice fed water. These data indicate that SMP, but not WPC, modulates faecal shedding in C. rodentium-infected mice and may impact progression of C. rodentium infection independently of selected bioactive concentration. This suggests that food matrix can impact biological effects of foods

MAIT cells are imprinted by the microbiota in early life and promote tissue repair

How early-life colonization and subsequent exposure to the microbiota affect long-term tissue immunity remains poorly understood. Here, we show that the development of mucosal-associated invariant T (MAIT) cells relies on a specific temporal window, after which MAIT cell development is permanently impaired. This imprinting depends on early-life exposure to defined microbes that synthesize riboflavin-derived antigens. In adults, cutaneous MAIT cells are a dominant population of interleukin-17A (IL-17A)-producing lymphocytes, which display a distinct transcriptional signature and can subsequently respond to skin commensals in an IL-1-, IL-18-, and antigen-dependent manner. Consequently, local activation of cutaneous MAIT cells promotes wound healing. Together, our work uncovers a privileged interaction between defined members of the microbiota and MAIT cells, which sequentially controls both tissue-imprinting and subsequent responses to injury

Rôle de l'interferon-gamma dans l'immunité cellulaire anti-microsporidienne. Etude du modèle de la souris déficiente pour le récepteur à l'interferon-gamma, infectée oralement avec la microsporidie Encephalitozoon intestinalis

Pr Dominique Mazier (Présidente), Dr Dominique Buzoni-Gatel (Rapporteur), Pr Christian Vivarès (Rapporteur), Pr Martin Danis (Examinateur), Pr Jean Dupouy-Camet (Examinateur), Dr Isabelle Desportes-Livage (Directeur de thèse)The microsporidium Encephalitozoon intestinalis causes gastrointestinal disease frequently associated with other clinical manifestations in immunocompromised HIV-infected patients. The intestinal mucosa provides the first physiological and immunological line of defense against the parasite. Nevertheless, most of what is known about the immunobiology of microsporidia results from studies realized with mice infected by the intraperitoneal route. Protection against these parasites has been largely associated with the cell-mediated immune response and the production of Th1-type cytokines, in particular gamma interferon (IFN-g). However, the mechanisms whereby IFN-g intervenes in the clearance of microsporidia are still not well understood. We therefore studied and compared the cellular immune response in wild-type and IFN-g receptor knockout (GRKO) mice following oral infection with E. intestinalis. First, we observed in infected wild-type mice which are able to control and eradicate the parasite, 1) the development of a Th1-type cellular immune response at the mucosal level, in the mesenteric lymph nodes and in the spleen; 2) the duodenal production of chemokines known to attract T lymphocytes and macrophages; and 3) an increase in the number of intestinal intraepithelial lymphocytes, which are able to exert cytotoxic activity against E. intestinalis-infected macrophages. In contrast, we showed in GRKO mice 1) a change in the pattern of chemokine expression at the mucocal level;2) a defect in the Th1-type cytokine expression and an earlier and/or higher expression of Th2-type cytokines; and finally 3) a less effective splenic cytotoxic T CD8+ response. Altogether, these results allow us to better understand the role of IFN-g in the antimicrosporidial immunity.La microsporidie Encephalitozoon intestinalis est la cause de diarrhées fréquemment associées à d'autres manifestations, chez les sujets immunodéprimés infectés par le VIH. La muqueuse intestinale constitue la première barrière physiologique et immunologique s'opposant à l'entrée du parasite dans l'organisme. Pourtant, la majorité des connaissances concernant l'immunobiologie des microsporidies résulte d'études effectuées chez la souris infectée par la voie intra-péritonéale. L'immunité protectrice vis-à-vis des microsporidies a largement été associée à la réponse immune cellulaire et à la production de cytokines de type Th1, et plus particulièrement d'IFN-g. Cependant, le ou les mécanismes par lequel l'IFN-g intervient dans le contrôle des microsporidioses reste encore mal caractérisé. Nous avons donc étudié et comparé la réponse immune cellulaire chez les souris sauvages et chez les souris déficientes pour le récepteur à l'IFN-g (GRKO), après infection orale avec E. intestinalis. Dans un premier temps, nous avons observé chez les souris sauvages infectées, capable de contrôler et d'éradiquer le parasite, 1) la mise en place d'une réponse immune cellulaire de type Th1 au niveau de la muqueuse intestinale, des ganglions mésentériques et de la rate ; 2) la production au niveau du duodenum de chimiokines connues pour attirer les lymphocytes T et les macrophages ; et 3) une augmentation du nombre de lymphocytes intraépithéliaux intestinaux, capables d'exercer une activité cytotoxique contre des macrophages infectés par le parasite. Chez les souris GRKO infectées, nous avons montré 1) une altération du profil d'expression des chimiokines au niveau de la muqueuse intestinale ; 2) un défaut d'expression des cytokines Th1 et une expression plus précoce et/ou plus importante des cytokines Th2 au niveau de tous les compartiments étudiés ; et 3) une réponse splénique T CD8+ cytotoxique moins efficace. L'ensemble de ces résultats nous permet de mieux cerner le rôle de l'IFN-g dans l'immunité anti-microsporidienne

Rôle de l'interferon-g(IFN-g) dans l'immunité cellulaire anti-microsporidienne (étude du modèle de la souris déficiente pour le récepteur à l'IFN-g, infectée oralement avec la microsporidie Encephalitozoon intestinalis)

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Microbe-dendritic cell dialog controls regulatory T-cell fate.

Each microenvironment is controlled by a specific set of regulatory elements that have to be finely and constantly tuned to maintain local homeostasis. These environments could be site specific, such as the gut environment, or induced by chronic exposure to microbes. Various populations of dendritic cells are central to the orchestration of this control. In this review, we discuss some new findings associating dendritic cells from defined compartments with the induction and control of regulatory T cells in the context of exposure to both commensal and pathogenic microbes.FLWINinfo:eu-repo/semantics/publishe