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

PLoS Pathogens

Mélina Smans¹  Tania Charpentier¹  Simona Stäger¹  Akil Hammami¹ 

[1] INRS—Institut Armand-Frappier, Laval, Quebec, Canada

关键词: T cells;    Cytotoxic T cells;    Leishmania donovani;    Parasitic diseases;    Inflammation;    Amastigotes;    Spleen;    Cytokines;   

DOI  :  10.1371/journal.ppat.1004938

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY