TRIF Licenses Caspase-11-Dependent NLRP3 Inflammasome Activation by Gram-Negative Bacteria

By Vijay A. K. Rathinam, S. Vanaja, Lisa Waggoner, Anna Sokolovska, Christine E. Becker, L. Stuart, J. Leong, Katherine A. Fitzgerald. Cell, 2012

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SUMMARY 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.

Subfields: Immunology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3f330ab777c6552888d3e12f2d2db6a9a50ea6f6

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Citations in the corpus

Inflammasome - activated gasdermin D causes pyroptosis by forming membrane pores (2016, background): “Pe lle t Triglyceride Diacylglycerol Phosphatidic acid Phosphatidylserine Phosphatidylethanolamine Phosphatidylcholine Phosphatidylglycerol Cardiolipin Blue blank Phosphatidylinositol PtdIns(4)P PtdIns(4,5)P2 PtdIns(3,4,5)P3 Cholesterol Sphingomyelin Sulfatide a”
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