IRF-5-Mediated Inflammation Limits CD8 T Cell Expansion by Inducing HIF-1α and Impairing Dendritic Cell Functions during Infection
Inflammation is essential for inducing, sustaining, and regulating CD8+ T cell responses. The transcription factor IRF-5 is mainly responsible for initiating the inflammatory response following experimental Leishmani donovani infection. IRF-5 activates several genes encoding key pro-inflammatory cytokines, such as IL-6 and TNF. In this study, 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 the expansion CD8+ T cell. This negative effect is mediated by the induction of HIF-1α in dendritic cells. Indeed, we observed a significant increase in CD8+ T cell expansion in mice lacking HIF-1α expression in dendritic cells. Moreover, these mice had a significantly lower parasite burden in the spleen, suggesting that induction of HIF-1α may represent an immune evasive mechanism adopted by Leishmania parasites to establish persistent infections.
Vyšlo v časopise:
IRF-5-Mediated Inflammation Limits CD8 T Cell Expansion by Inducing HIF-1α and Impairing Dendritic Cell Functions during Infection. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004938
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004938
Souhrn
Inflammation is essential for inducing, sustaining, and regulating CD8+ T cell responses. The transcription factor IRF-5 is mainly responsible for initiating the inflammatory response following experimental Leishmani donovani infection. IRF-5 activates several genes encoding key pro-inflammatory cytokines, such as IL-6 and TNF. In this study, 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 the expansion CD8+ T cell. This negative effect is mediated by the induction of HIF-1α in dendritic cells. Indeed, we observed a significant increase in CD8+ T cell expansion in mice lacking HIF-1α expression in dendritic cells. Moreover, these mice had a significantly lower parasite burden in the spleen, suggesting that induction of HIF-1α may represent an immune evasive mechanism adopted by Leishmania parasites to establish persistent infections.
Zdroje
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