TLR Agonists That Induce IFN-β Abrogate Resident Macrophage Suppression of T Cells
TLR Agonists That Induce IFN-β Abrogate Resident Macrophage Suppression of T Cells
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DOI：
10.4049/jimmunol.1002045
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发表时间：
2010-10-15
影响因子：
4.4
通讯作者：
Krystal, Gerald
中科院分区：
文献类型：
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作者：
Hamilton, Melisa J.;Antignano, Frann;Krystal, Gerald
常驻组织巨噬细胞 (M phi s) 不断地调查微环境，摄取 Ag 并将其呈现在其表面以供 T 细胞识别。因为这些 Ag 可以是宿主细胞衍生的，也可以是病原体衍生的，M phi 必须能够区分特定 Ag 是否应该引起免疫反应或被耐受。然而，决定 M phi 促进还是抑制 T 细胞活化的机制尚不清楚。为了研究这一点，我们首先确定了在没有病原体的情况下小鼠腹腔 M phi 抑制体外 T 细胞增殖的机制，然后探讨了不同病原体衍生分子对 M phi 免疫抑制的影响。我们的结果表明，响应 TCR 激活的 T 细胞分泌的 IFN-γ，常驻腹膜 M phi 获得由 NO 介导的免疫抑制特性。然而，用 LPS 或 dsRNA（而不是 CpG 或肽聚糖）预处理 M phi 可以消除它们的抑制特性，部分是通过诱导自分泌作用的 IFN-β。这些结果表明，激活 TRIF 并因此诱导 IFN-β 的 TLR 激动剂（但不是那些专门通过 MyD88 发出信号的 TLR 激动剂）消除了 Mphi 的免疫抑制特性，从而促进 T 细胞扩增和消除入侵微生物。免疫学杂志，2010，185：4545-4553。
Resident tissue macrophages (M phi s) continually survey the microenvironment, ingesting Ags and presenting them on their surface for recognition by T cells. Because these Ags can be either host cell-or pathogen-derived, M phi s must be able to distinguish whether a particular Ag should provoke an immune response or be tolerated. However, the mechanisms that determine whether M phi s promote or inhibit T cell activation are not well understood. To investigate this, we first determined the mechanism by which murine resident peritoneal M phi s suppress in vitro T cell proliferation in the absence of pathogens and then explored the effects of different pathogen-derived molecules on M phi immunosuppression. Our results suggest that, in response to IFN-gamma, which is secreted by TCR-activated T cells, resident peritoneal M phi s acquire immunosuppressive properties that are mediated by NO. However, pretreatment of M phi s with LPS or dsRNA, but not CpG or peptidoglycan, eliminates their suppressive properties, in part via the induction of autocrine-acting IFN-beta. These results suggest TLR agonists that activate TRIF, and consequently induce IFN-beta, but not those that exclusively signal through MyD88, abrogate the immunosuppressive properties of M phi s, and thus promote T cell expansion and elimination of invading microorganisms. The Journal of Immunology, 2010, 185: 4545-4553.