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Origine et rôles des cellules myéloïdes suppressives dans le sepsis

Abstract : Myeloid-Derived Suppressor Cells (MDSC) are a heterogeneous population of immature myeloid cell, and are regrouped in two subsets: the monocytic-MDSC (M-MDSC) and the polymorphonuclear-MDSC (PMN-MDSC). These cells have immunosuppressive capacities and mainly act on T cells. MDSC can express the ligand PD-L1 and induce PD-1 expressing-T cells exhaustion. During sepsis, several immunological changes occur, and MDSC probably downregulate the hyper-inflammatory state, contributing to the immunosuppression phase encountered in patients after a sepsis. Immunocompromised patients can develop secondary infections, and reactivate latent virus. The aims of our study were to highlight the origin of MDSC in sepsis, and to explore their roles in the immunosuppression state, especially in the Torque Teno Virus (TTV) reactivation. Our results show, both ex vivo and in vitro, that in sepsis, MDSC originate from bone marrow are induced by G-CSF and IL-6. These PD-L1 expressing-cells are increased in peripheral blood very early in sepsis, and persist during hospitalization. These MDSC are able to inhibit T cells in vitro. The increase of TTV viral load is observed in peripheral blood of patients but is not correlated with MDSC frequencies. These results suggest that during sepsis, the cytokine storm boosts PD-L1 expressing MDSC’s production by bone marrow, which contribute in peripheral blood to the immunosuppression
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Emilie Lereclus. Origine et rôles des cellules myéloïdes suppressives dans le sepsis. Médecine humaine et pathologie. Université de Limoges, 2018. Français. ⟨NNT : 2018LIMO0060⟩. ⟨tel-02440666⟩

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