INRS-Institut Armand-Frappier, 531 Boulevard des Prairies, Laval, QC H7V 1B7, Canada.
INRS-Institut Armand-Frappier, 531 Boulevard des Prairies, Laval, QC H7V 1B7, Canada.
Cell Rep. 2018 Jul 31;24(5):1163-1175. doi: 10.1016/j.celrep.2018.06.107.
The transcription factor interferon regulatory factor 5 (IRF-5) plays an important function in innate immunity and in initiating pro-inflammatory responses against pathogens. IRF-5 is constitutively expressed in several cell types, including plasmacytoid dendritic cells, monocytes, and B cells. We have previously reported that IRF-5 is also expressed in T cells during infection. The role of IRF-5 in T cells is yet unknown. Here, we demonstrate that IRF-5 is increasingly expressed in interferon (IFN)-γ CD4 T cells over the course of L. donovani infection. This transcription factor is induced by apoptotic material via Toll-like receptor 7 (TLR7) and promotes the expression of death receptor 5 (DR5). IRF-5 activation sensitizes CD4 T cells to cell death. Because tissue disruption and chronic inflammation are common characteristics of persistent infections, activation of IRF-5 in CD4 T cells may represent a common pathway that leads to suppression of protective CD4 T cell responses, favoring the establishment of chronic infection.
转录因子干扰素调节因子 5（IRF-5）在先天免疫和启动针对病原体的促炎反应中发挥重要作用。IRF-5 在几种细胞类型中持续表达，包括浆细胞样树突状细胞、单核细胞和 B 细胞。我们之前报道过，IRF-5 在感染期间也在 T 细胞中表达。IRF-5 在 T 细胞中的作用尚不清楚。在这里，我们证明在 L. 感染过程中，IRF-5 在 IFN-γ CD4 T 细胞中的表达逐渐增加。这种转录因子通过 Toll 样受体 7（TLR7）被凋亡物质诱导，并促进死亡受体 5（DR5）的表达。IRF-5 的激活使 CD4 T 细胞对细胞死亡敏感。因为组织破坏和慢性炎症是持续性感染的共同特征，所以 CD4 T 细胞中 IRF-5 的激活可能代表了导致保护性 CD4 T 细胞反应受到抑制的共同途径，有利于慢性感染的建立。
