NOD-Like Receptors in Innate Immune Responses
Summary
Nucleotide-binding oligomerisation domain (NOD)-like receptors (NLRs) constitute a family of cytosolic pattern recognition receptors that survey the intracellular milieu for signs of infection, cellular stress and metabolic disturbance. Structurally, most NLRs share an N-terminal effector domain (such as a CARD or pyrin domain), a central NACHT nucleotide-binding domain and C-terminal leucine-rich repeats. Upon detection of microbial products or danger signals, NLRs initiate signalling cascades that activate nuclear factor-κB, mitogen-activated protein kinase pathways and interferon responses, driving the production of pro-inflammatory cytokines and chemokines. A subset of NLRs assembles into multiprotein inflammasomes that recruit and activate caspase-1, leading to interleukin-1β and interleukin-18 maturation and a lytic form of cell death known as pyroptosis. Beyond pathogen defence, NLRs regulate gut barrier integrity, neuroinflammation, autophagy and immunometabolism. Dysregulation of NLR function underlies a spectrum of autoinflammatory, metabolic and neurodegenerative disorders. The recent elucidation of ligand-binding modes, oligomerisation interfaces and downstream effector interactions is guiding the development of targeted modulators with translational potential in infection, chronic inflammation and metabolic disease.
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NOD-Like Receptors in Innate Immune Responses publication trend
The graph below shows the total number of articles in nod-like receptors in innate immune responses across all publications each year (not limited to Nature Index journals).
Technical terms
NOD-like receptor (NLR): A cytosolic pattern recognition receptor with NACHT and leucine-rich repeat domains that senses intracellular threats.
Inflammasome: A multiprotein complex formed by certain NLRs that activates caspase-1 to process pro-inflammatory cytokines and induce pyroptosis.
Pyroptosis: A form of programmed cell death associated with inflammasome activation, characterised by cell swelling and release of inflammatory mediators.
PAMP/DAMP: Pathogen-associated molecular pattern or damage-associated molecular pattern; conserved molecules indicating infection or cellular injury.
Immunometabolism: The study of how cellular metabolic processes influence and are regulated by immune signalling pathways.
References
- Functions of NOD-Like Receptors in Human Diseases. Frontiers in Immunology (2013).
- Molecular mechanisms of emerging inflammasome complexes and their activation and signaling in inflammation and pyroptosis. Immunological Reviews (2024).
- Impact of intracellular innate immune receptors on immunometabolism. Cellular & Molecular Immunology (2021).
- NLRP12 Regulates Anti-viral RIG-I Activation via Interaction with TRIM25. Cell Host & Microbe (2019).
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