Toll-like receptor-mediated induction of type I interferon in plasmacytoid dendritic cells requires the rapamycin-sensitive PI(3) K-mTOR-p70S6K pathway

被引：333

作者：

Cao, Weiping ^{[1
]}

Manicassamy, Santhakumar ^{[1
]}

Tang, Hua ^{[1
]}

Kasturi, Sudhir Pai ^{[1
]}

Pirani, Ali ^{[2
]}

Murthy, Niren ^{[3
]}

Pulendran, Bali ^{[1
,4
]}

机构：

[1] Emory Vaccine Ctr, Atlanta, GA 30329 USA

[2] Emory Univ, Sch Med, Atlanta, GA 30322 USA

[3] Georgia Inst Technol, Dept Biomed Engn, Atlanta, GA 30332 USA

[4] Emory Univ, Dept Pathol, Atlanta, GA 30322 USA

来源：

NATURE IMMUNOLOGY | 2008年 / 9卷 / 10期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1038/ni.1645

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Robust production of type I interferon (IFN-alpha/beta) in plasmacytoid dendritic cells (pDCs) is crucial for antiviral immunity. Here we show involvement of the mammalian target of rapamycin ( mTOR) pathway in regulating interferon production by pDCs. Inhibition of mTOR or its 'downstream' mediators, the p70 ribosomal S6 protein kinases p70S6K1 and p70S6K2, during pDC activation by Toll-like receptor 9 (TLR9) blocked the interaction of TLR9 with the adaptor MyD88 and subsequent activation of the interferon-regulatory factor IRF7, which resulted in impaired IFN-alpha/beta production. Microarray analysis confirmed that inhibition of mTOR by the immunosuppressive drug rapamycin suppressed antiviral and anti-inflammatory gene expression. Consistent with this, targeting rapamycin-encapsulated microparticles to antigen-presenting cells in vivo resulted in less IFN-alpha/beta production in response to CpG DNA or the yellow fever vaccine virus strain 17D. Thus, mTOR signaling is crucial in TLR-mediated IFN-alpha/beta responses by pDCs.

引用

页码：1157 / 1164

页数：8

共 40 条

[1] Mouse type IIFN-producing cells are immature APCs with plasmacytoid morphology [J].