Abstract
In this review we give an overview of the NAIP/NLRC4 activation mechanism as well as the described roles of this inflammasome, with a focus on in vivo infection and pathology. After ligand recognition by NAIP sensor proteins the NAIP/NLRC4 inflammasome forms through oligomerization with the NLRC4 adaptor to activate Caspase-1. The activating ligands are intracellular bacterial flagellin or type-3 secretion system components, delivered by pathogens. In vivo experiments indicate a role in macrophages during lung, spleen and liver infection and systemic sepsis like conditions, as well as in intestinal epithelial cells. Upon NAIP/NLRC4 activation in the intestine, epithelial cell extrusion is triggered in addition to the canonical inflammasome outcomes of cytokine cleavage and pyroptosis. Human patients with auto-activating mutations in NLRC4 present with an autoinflammatory syndrome including enterocolitis. Although one of the better understood inflammasomes in terms of mechanism, tissue specific functions of NAIP/NLRC4 are only beginning to be understood.
Original language | English (US) |
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Article number | 100863 |
Journal | Molecular Aspects of Medicine |
Volume | 76 |
DOIs | |
State | Published - Dec 2020 |
Keywords
- Caspase
- Inflammasome
- NAIP
- NLRC4
- bacterial infection
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Clinical Biochemistry