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Regulation of the Acute Sickness Response by the P2RX7 Receptor
Hui Li1, Erin Cvejic2, Ben Gu3
1Viral Immunology Systems Program, Kirby Institute, University of New South Wales, Sydney, Australia.
The Journal of Infectious Diseases
|January 20, 2021
Summary
The P2RX7 gene influences sickness responses to infection. Specific P2RX7 gene variants are linked to illness severity, fatigue, pain, and mood disturbances, highlighting its role in the immune system and brain.
Area of Science:
- Immunology
- Neuroscience
- Genetics
Background:
- The acute sickness response to infection involves peripheral proinflammatory signals and central mediation.
- The P2RX7 gene, encoding an ATP-gated ion channel, is expressed in immune cells and the brain, regulating the NLRP3 inflammasome and neural functions.
Purpose of the Study:
- To investigate associations between P2RX7 genotype, pore activity, and illness manifestations in patients with acute infections.
- To explore the role of P2RX7 signaling in the central mediation of sickness responses.
Main Methods:
- Genotyping of 12 P2RX7 single-nucleotide polymorphisms (SNPs) and haplotype/diplotype analysis in 484 patients with acute infections.
- Measurement of leukocyte pore activity (YO-PRO-1 uptake) and IL-1β release.
- Correlation of genetic data with illness symptom domains (endophenotypes) derived from principal components analysis.
Main Results:
- A 4-SNP haplotype block with 5 variants was identified in 99.5% of subjects, closely associated with P2RX7 pore activity and IL-1β production.
- Homozygous P2RX7 diplotypes were significantly associated with overall illness severity, fatigue, pain, and mood disturbances.
Conclusions:
- P2RX7 signaling is crucial in the acute sickness response to infection.
- P2RX7 likely exerts its effects within both the immune system and the central nervous system.
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