Abstract : Inflammation is known to be necessary for promoting, sustaining, and tuning CD8+ T cell responses. Following experimental Leishmania donovani infection, the inflammatory response is mainly induced by the transcription factor IRF-5. IRF-5 is responsible for the activation of several genes encoding key pro-inflammatory cytokines, such as IL-6 and TNF. Here, we investigate the role of IRF-5-mediated inflammation in regulating antigen-specific CD8+ T cell responses during L. donovani infection. Our data demonstrate that the inflammatory response induced by IRF-5 limits CD8+ T cell expansion and induces HIF-1α in dendritic cells. Ablation of HIF-1α in CD11c+ cells resulted into a higher frequency of short-lived effector cells (SLEC), enhanced CD8+ T cell expansion, and increased IL-12 expression by splenic DCs. Moreover, mice with a targeted depletion of HIF-1α in CD11c+ cells had a significantly lower splenic parasite burden, suggesting that induction of HIF-1α may represent an immune evasive mechanism adopted by Leishmania parasites to establish persistent infections.
https://hal-riip.archives-ouvertes.fr/pasteur-01352161
Contributeur : Michel Courcelles
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Soumis le : vendredi 5 août 2016 - 16:53:43
Dernière modification le : lundi 8 octobre 2018 - 17:44:05
