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Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
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Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells

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The NLR family of innate immune and cell death sensors

Balamurugan Sundaram1, Rebecca E Tweedell1, Sivakumar Prasanth Kumar1

  • 1Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Immunity
|April 10, 2024
PubMed

Insights

Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are crucial cytosolic pattern recognition receptors. Understanding NLR networks in cell death and immunity offers potential therapeutic strategies for various diseases.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are cytosolic pattern recognition receptors sensing pathogenic and sterile triggers.
  • NLR activation initiates inflammatory signaling, inflammasome formation, and pyroptosis, a form of lytic cell death.
  • Some NLRs and inflammasomes contribute to PANoptosomes, driving PANoptosis, another lytic cell death pathway.

Purpose of the Study:

  • To review the current understanding of NLR evolution, structure, and function.
  • To discuss NLR networks and their roles in immunity and cell death.
  • To highlight the therapeutic potential of NLRs in infectious, inflammatory diseases, and cancer.

Main Methods:

  • Literature review of NLRs, inflammasomes, and related cell death pathways.
  • Analysis of NLR networks and their involvement in immune responses.
  • Synthesis of current knowledge on NLRs in health and disease.

Main Results:

  • NLRs are central to innate immunity, detecting diverse triggers and initiating inflammatory responses.
  • Inflammasomes, regulated by NLRs, are key mediators of pyroptosis and cytokine maturation.
  • NLRs and inflammasomes are integral to PANoptosomes, governing PANoptosis.

Conclusions:

  • NLRs play multifaceted roles in immunity and cell death, forming complex regulatory networks.
  • A deeper mechanistic insight into NLRs can unlock novel therapeutic avenues.
  • Targeting NLRs holds promise for treating infectious diseases, inflammatory conditions, and cancer.
Keywords:
DAMPIL-18IL-1βNF-κBNLRNLR networkPAMPPANoptosisPANoptosomeRIPKapoptosiscaspase-1gasdermininflammasomeinflammatory cell deathinnate immune cell deathinterferonnecroptosispattern recognition receptorpyroptosis

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