Modulation de l'immunité adaptative murine par la micropesanteur simulée, l'hypergravité ou les stress chroniques ultra légers

Abstract : Spaceflight weaken the immune system. The aims of this thesis were to determine the effects of exposure to simulated microgravity, hypergravity or chronic ultra-mild stress on murine humoral immunity, using ground-based models. We were able to show that the anti-orthostatic suspension, that mimics some of the effects of microgravity, caused a 59% decrease of the number of splenic B cells and an inversion of the ratio between B and T lymphocytes. A decrease in B lymphopoiesis, as evidenced by the decrease of lymphoid progenitors and pre-B cells is likely the cause. Furthermore, we showed that the anti-orthostatic position, in the absence of stress, leads to a decreased in vitro response of B cells to LPS, more important than the one of T cells to ConA, as did hypergravity exposure. To determine the mechanisms responsible of the decreased response of B cells from hypergravity mice, transcripts encoding genes involved in the TLR-4 signaling pathway, the LPS receptor on B cells, have been quantified. The expression of several genes of the MyD88-dependent pathway was increased after 21 days of hypergravity, but no change was observed in B cells stimulated with LPS. Finally, the contribution of chronic ultra-mild stresses was evaluated. The proportions of splenic lymphocytes were not affected by these stresses. However, the levels of serum IgA were increased and those of Th1 pro-inflammatory cytokines were decreased, as in astronauts. Thus, these stresses do not fully explain the negative impact of spaceflight conditions on humoral immunity. These researches are important to identify the cause(s) of spaceflight-associated impaired immunity in order to test/develop effective countermeasures to strengthen the immune system of astronauts, but also of stressed or elderly people
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Fanny Gaignier. Modulation de l'immunité adaptative murine par la micropesanteur simulée, l'hypergravité ou les stress chroniques ultra légers. Médecine humaine et pathologie. Université de Lorraine, 2014. Français. ⟨NNT : 2014LORR0171⟩. ⟨tel-01751064⟩

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