当前位置: X-MOL 学术J. Immunol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Cutting Edge: TNF Is Essential for Mycobacteria-Induced MINCLE Expression, Macrophage Activation, and Th17 Adjuvanticity
The Journal of Immunology ( IF 4.4 ) Pub Date : 2020-06-15 , DOI: 10.4049/jimmunol.2000420
Judith Schick 1 , Johanna Schäfer 1 , Christian Alexander 2 , Stefanie Dichtl 3 , Peter J Murray 3 , Dennis Christensen 4 , Ursula Sorg 5 , Klaus Pfeffer 5 , Ulrike Schleicher 1 , Roland Lang 6
Affiliation  

Key Points TNF is required for mycobacteria-induced upregulation of MINCLE and DECTIN-2. Inhibition of TNF in vivo abrogates Th17 responses by a MINCLE-dependent adjuvant. Visual Abstract TNF blockade is a successful treatment for human autoimmune disorders like rheumatoid arthritis and inflammatory bowel disease yet increases susceptibility to tuberculosis and other infections. The C-type lectin receptors (CLR) MINCLE, MCL, and DECTIN-2 are expressed on myeloid cells and sense mycobacterial cell wall glycolipids. In this study, we show that TNF is sufficient to upregulate MINCLE, MCL, and DECTIN-2 in macrophages. TNF signaling through TNFR1 p55 was required for upregulation of these CLR and for cytokine secretion in macrophages stimulated with the MINCLE ligand trehalose-6,6-dibehenate or infected with Mycobacterium bovis bacillus Calmette–Guérin. The Th17 response to immunization with the MINCLE-dependent adjuvant trehalose-6,6-dibehenate was specifically abrogated in TNF-deficient mice and strongly attenuated by TNF blockade with etanercept. Together, interference with production or signaling of TNF antagonized the expression of DECTIN-2 family CLR, thwarting vaccine responses and possibly increasing infection risk.

中文翻译:

前沿:TNF 对于分枝杆菌诱导的 MINCLE 表达、巨噬细胞激活和 Th17 佐剂性至关重要

要点 分枝杆菌诱导的 MINCLE 和 DECTIN-2 上调需要 TNF。体内 TNF 的抑制消除了 MINCLE 依赖性佐剂的 Th17 反应。Visual Abstract TNF 阻断剂可成功治疗类风湿性关节炎和炎症性肠病等人类自身免疫性疾病,但会增加对结核病和其他感染的易感性。C 型凝集素受体 (CLR) MINCLE、MCL 和 DECTIN-2 在骨髓细胞上表达并感知分枝杆菌细胞壁糖脂。在这项研究中,我们表明 TNF 足以上调巨噬细胞中的 MINCLE、MCL 和 DECTIN-2。通过 TNFR1 p55 的 TNF 信号传导是这些 CLR 的上调以及被 MINCLE 配体海藻糖-6,6-二山萮酸酯刺激或被牛分枝杆菌 Calmette-Guérin 感染的巨噬细胞中的细胞因子分泌所必需的。Th17 对用 MINCLE 依赖性佐剂 trehalose-6,6-dibehenate 免疫的反应在 TNF 缺陷小鼠中被特异性消除,并被依那西普的 TNF 阻断强烈减弱。总之,干扰 TNF 的产生或信号传导会拮抗 DECTIN-2 家族 CLR 的表达,阻碍疫苗反应并可能增加感染风险。
更新日期:2020-06-15
down
wechat
bug