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

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. © 2015 hammami et al.