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Etude du rôle des Lymphocytes Intraépithéliaux innés dans la réponse immune protectrice contre Cryptosporidium parvum

Abstract : 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.
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Submitted on : Friday, May 13, 2022 - 6:45:02 PM
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Fatima Hariss. Etude du rôle des Lymphocytes Intraépithéliaux innés dans la réponse immune protectrice contre Cryptosporidium parvum. Médecine humaine et pathologie. Université de Lille; Université Libanaise, 2021. Français. ⟨NNT : 2021LILUS047⟩. ⟨tel-03667962⟩

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