The NAIP/NLRC4 inflammasome in infection and pathology.

Renate Bauer, Isabella Rauch

Journal: Molecular aspects of medicine 2021;76():100863

PMID: 32499055

Full Text on Elsevier Science View on PubMed

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.

Address: Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR, USA; Department of Biosciences, University of Salzburg, A-5020, Salzburg, Austria.; Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, OR, USA. Electronic address: [email protected].

DOI: 10.1016/j.mam.2020.100863

Link outs

Subscription / membership required

Full Text Sources:

https://linkinghub.elsevier.com/retrieve/pii/S0098...

MeSH Terms: CARD Signaling Adaptor Proteins, Calcium-Binding Proteins, Flagellin, Humans, Immunity, Innate, Inflammasomes, Neuronal Apoptosis-Inhibitory Protein