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IRF-5-Mediated Inflammation Limits CD8+ T Cell Expansion by Inducing HIF-1alpha and Impairing Dendritic Cell Functions during Leishmania Infection

Hammami, Akil; Charpentier, Tania; Smans, Mélina; Stäger, Simona (2015). IRF-5-Mediated Inflammation Limits CD8+ T Cell Expansion by Inducing HIF-1alpha and Impairing Dendritic Cell Functions during Leishmania Infection PLoS Pathogens , vol. 11 , nº 6. e1004938. DOI: 10.1371/journal.ppat.1004938.

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Résumé

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-1alpha in dendritic cells. Ablation of HIF-1alpha 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-1alpha in CD11c+ cells had a significantly lower splenic parasite burden, suggesting that induction of HIF-1alpha may represent an immune evasive mechanism adopted by Leishmania parasites to establish persistent infections.

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Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 09 mars 2016 16:10
Dernière modification: 09 mars 2016 16:10
URI: http://espace.inrs.ca/id/eprint/3321

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