Details

Autor(en) / Beteiligte

• Wu, Junru
• Cai, Jingjing
• Tang, Yiting
• Lu, Ben

Titel

The noncanonical inflammasome-induced pyroptosis and septic shock

Ist Teil von

• Seminars in immunology, 2023-11, Vol.70, p.101844-101844, Article 101844

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Sepsis remains one of the most common and lethal conditions globally. Currently, no proposed target specific to sepsis improves survival in clinical trials. Thus, an in-depth understanding of the pathogenesis of sepsis is needed to propel the discovery of effective treatment. Recently attention to sepsis has intensified because of a growing recognition of a non-canonical inflammasome-triggered lytic mode of cell death termed pyroptosis upon sensing cytosolic lipopolysaccharide (LPS). Although the consequences of activation of the canonical and non-canonical inflammasome are similar, the non-canonical inflammasome formation requires caspase-4/5/11, which enzymatically cleave the pore-forming protein gasdermin D (GSDMD) and thereby cause pyroptosis. The non-canonical inflammasome assembly triggers such inflammatory cell death by itself; or leverages a secondary activation of the canonical NLRP3 inflammasome pathway. Excessive cell death induced by oligomerization of GSDMD and NINJ1 leads to cytokine release and massive tissue damage, facilitating devastating consequences and death. This review summarized the updated mechanisms that initiate and regulate non-canonical inflammasome activation and pyroptosis and highlighted various endogenous or synthetic molecules as potential therapeutic targets for treating sepsis. •Non-canonical inflammasome-induced pyroptosis may contribute to excessive inflammatory response in septic shock.•Cytosolic LPS delivery and sensing mediate non-canonical inflammasome activation.•Interaction between non-canonical inflammasome activation and dysregulated coagulation system in septic shock.•Emerging therapeutic targets for sepsis from regulation of the non-canonical inflammasome pathway.