Skip to Content
MilliporeSigma
  • AIM2 forms a complex with pyrin and ZBP1 to drive PANoptosis and host defence.

AIM2 forms a complex with pyrin and ZBP1 to drive PANoptosis and host defence.

Nature (2021-09-03)
SangJoon Lee, Rajendra Karki, Yaqiu Wang, Lam Nhat Nguyen, Ravi C Kalathur, Thirumala-Devi Kanneganti
ABSTRACT

Inflammasomes are important sentinels of innate immune defence, sensing pathogens and inducing cell death in infected cells1. There are several inflammasome sensors that each detect and respond to a specific pathogen- or damage-associated molecular pattern (PAMP or DAMP, respectively)1. During infection, live pathogens can induce the release of multiple PAMPs and DAMPs, which can simultaneously engage multiple inflammasome sensors2-5. Here we found that AIM2 regulates the innate immune sensors pyrin and ZBP1 to drive inflammatory signalling and a form of inflammatory cell death known as PANoptosis, and provide host protection during infections with herpes simplex virus 1 and Francisella novicida. We also observed that AIM2, pyrin and ZBP1 were members of a large multi-protein complex along with ASC, caspase-1, caspase-8, RIPK3, RIPK1 and FADD, that drove inflammatory cell death (PANoptosis). Collectively, our findings define a previously unknown regulatory and molecular interaction between AIM2, pyrin and ZBP1 that drives assembly of an AIM2-mediated multi-protein complex that we term the AIM2 PANoptosome and comprising multiple inflammasome sensors and cell death regulators. These results advance the understanding of the functions of these molecules in innate immunity and inflammatory cell death, suggesting new therapeutic targets for AIM2-, ZBP1- and pyrin-mediated diseases.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-ASC Antibody, clone 2EI-7, clone 2EI-7, from mouse
Sign Into View Organizational & Contract Pricing
SKUPack SizeAvailabilityPriceQuantity
10 mL
In Stock
Details...
$589.00
Sigma-Aldrich
Colchicine, ≥95% (HPLC), powder
Sign Into View Organizational & Contract Pricing
SKUPack SizeAvailabilityPriceQuantity
10 mL
In Stock
Details...
$589.00
Sigma-Aldrich
Anti-FADD Antibody, clone 1F7, clone 1F7, Upstate®, from mouse
Sign Into View Organizational & Contract Pricing
SKUPack SizeAvailabilityPriceQuantity
10 mL
In Stock
Details...
$589.00
Millipore
MILLIPLEX® Mouse Cytokine/Chemokine Magnetic Bead Panel - Immunology Multiplex Assay, Simultaneously analyze multiple cytokine and chemokine biomarkers with Bead-Based Multiplex Assays using the Luminex technology, in mouse serum, plasma and cell culture samples.
Sign Into View Organizational & Contract Pricing
SKUPack SizeAvailabilityPriceQuantity
10 mL
In Stock
Details...
$589.00