共 46 条
TRIF Licenses Caspase-11-Dependent NLRP3 Inflammasome Activation by Gram-Negative Bacteria
被引:584
作者:

Rathinam, Vijay A. K.
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Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA

Vanaja, Sivapriya Kailasan
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机构:
Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA
Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA

Waggoner, Lisa
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Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA

Sokolovska, Anna
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Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA

Becker, Christine
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Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA

Stuart, Lynda M.
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Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA

Leong, John M.
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机构:
Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA

Fitzgerald, Katherine A.
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h-index: 0
机构:
Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA
机构:
[1] Univ Massachusetts, Sch Med, Dept Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA
[2] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA
[3] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA
来源:
关键词:
NF-KAPPA-B;
CASPASE-1;
ACTIVATION;
GENE-EXPRESSION;
CELL-DEATH;
ASC;
APOPTOSIS;
RECEPTOR;
TRAM;
INTERLEUKIN-1-BETA;
RECOGNITION;
D O I:
10.1016/j.cell.2012.07.007
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Systemic infections with Gram-negative bacteria are characterized by high mortality rates due to the "sepsis syndrome," a widespread and uncontrolled inflammatory response. Though it is well recognized that the immune response during Gram-negative bacterial infection is initiated after the recognition of endotoxin by Toll-like receptor 4, the molecular mechanisms underlying the detrimental inflammatory response during Gram-negative bacteremia remain poorly defined. Here, we identify a TRIF pathway that licenses NLRP3 inflammasome activation by all Gram-negative bacteria. By engaging TRIF, Gram-negative bacteria activate caspase-11. TRIF activates caspase-11 via type I IFN signaling, an event that is both necessary and sufficient for caspase-11 induction and autoactivation. Caspase-11 subsequently synergizes with the assembled NLRP3 inflammasome to regulate caspase-1 activation and leads to caspase-1-independent cell death. These events occur specifically during infection with Gram-negative, but not Gram-positive, bacteria. The identification of TRIF as a regulator of caspase-11 underscores the importance of TLRs as master regulators of inflammasomes during Gram-negative bacterial infection.
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页码:606 / 619
页数:14
相关论文
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h-index: 0
机构:
Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland

Braun, Marion
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Ludwig Inst Canc Res, CH-1011 Lausanne, Switzerland Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland

Staehli, Francesco
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Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland

Tardivel, Aubry
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Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland

Mattmann, Chantal
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Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland

Foerster, Irmgard
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机构:
Univ Dusseldorf, Inst Umweltmed Forsch gGmbH, D-40225 Dusseldorf, Germany Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland

Farlik, Matthias
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Univ Vienna, Max F Perutz Labs, Dept Genet Microbiol & Immunobiol, A-1030 Vienna, Austria Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland

Decker, Thomas
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Univ Vienna, Max F Perutz Labs, Dept Genet Microbiol & Immunobiol, A-1030 Vienna, Austria Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland

Du Pasquier, Renaud A.
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机构:
Univ Lausanne Hosp, Serv Neurol, Dept Clin Neurosci, CH-1011 Lausanne, Switzerland
Univ Lausanne Hosp, Serv Immunol, CH-1011 Lausanne, Switzerland Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland

Romero, Pedro
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Ludwig Inst Canc Res, CH-1011 Lausanne, Switzerland Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland

Tschopp, Juerg
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Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland