000173452 001__ 173452
000173452 005__ 20180913061039.0
000173452 037__ $$aSTUDENT
000173452 245__ $$aModulation of Dendritic Cells Function by H. polygyrus Products
000173452 269__ $$a2011
000173452 260__ $$c2011
000173452 336__ $$aStudent Projects
000173452 500__ $$aGlobal Health Institute, EPFL. - Carried out in Rick Maizels’ laboratory at the Institute of Infection and Immunology Research, University of Edinburgh, under the supervision of Rick Maizels
000173452 520__ $$aDendritic cells (DCs) are crucial antigen-presenting cells that can drastically change the development of an immune response by polarising T helper cells toward a Th1 or a Th2 phenotype. Heligmosomoides polygyrus, a murine model of human helminth, has been shown to strongly down-regulate its host immune response. At the DC level, its excretory/secretory products (HES) modulate the cytokine response and co-stimulatory marker expression to bacterial stimulation in favour of an antiinflammatory environment. A regulatory T cell-inducing TGF[beta]-like activity was also discovered in HES. In this work, we further characterised the immunomodulatory properties of HES and heat-inactivated HES both in vitro, using LPS-pulsed GM-CSF-grown bone marrowderived DCs, and in in vivo adoptive transfer of HES-, bacterial extract- or co-pulsed DCs. To determine if the TGF[beta], C-type lectin receptors (CLRs) or toll-like receptors (TLRs) were implicated in this immunomodulation, we treated DCs with blocking antibodies, chemical kinase inhibitors and grew DCs from knockout mice. These studies revealed that HES immunomodulation of DCs was independent of the TGF[beta] receptor, the two CLRs, Dectin-1 and 2, as well as any TLR. Spleen tyrosine kinase (Syk), which is crucial for the signalling of many CLRs, and phosphoinositide 3- kinase seemed not to be needed as well. In an attempt to reduce the number of potential immunomodulators in HES, HES size fractions were tested for their ability to reduce LPS-induced inflammatory cytokine production of DCs. The activity was limited to few fractions, fraction 14 being the most potent. Finally, physical interactions between DCs and biotinylated HES were measured by flow cytometry and revealed that CD24, a molecule required for HES interactions with B cells, was implicated, but not crucial. HES binding to CD24-/- DCs was reduced, but the LPS-induced cytokines and co-stimulatory markers levels were still down-regulated upon HES co-treatment.
000173452 6531_ $$aFSV/SSV
000173452 6531_ $$aLife Sciences and Technology
000173452 6531_ $$aSciences et Technologies du Vivant
000173452 700__ $$0(EPFLAUTH)175651$$aDayer, Blaise$$g175651
000173452 720_2 $$0243705$$aDoerig, Christian$$edir.$$g191299
000173452 720_2 $$0243703$$aHarris, Nicola$$edir.$$g196676
000173452 8564_ $$s23743302$$uhttps://infoscience.epfl.ch/record/173452/files/Blaise_Dayer-Master_Thesis-Final.pdf$$yn/a$$zn/a
000173452 909C0 $$0252289$$pSSV
000173452 909CO $$ooai:infoscience.tind.io:173452$$pSV
000173452 917Z8 $$x108898
000173452 937__ $$aEPFL-STUDENT-173452
000173452 973__ $$aEPFL$$sPUBLISHED
000173452 980__ $$aSTUDENT$$bMASTERS