Regulation of the Acute Sickness Response by the P2RX7 Receptor.
J Infect Dis
; 224(5): 914-920, 2021 09 01.
Article
em En
| MEDLINE
| ID: mdl-33471105
ABSTRACT
BACKGROUND:
The acute sickness response to infection is a stereotyped set of illness manifestations initiated by proinflammatory signals in the periphery but mediated centrally. P2RX7 is a highly polymorphic gene encoding an ATP-gated cationic pore, widely expressed on immune cells and the brain, and regulating the NLRP3 inflammasome, as well as diverse neural functions.METHODS:
Associations between P2RX7 genotype, pore activity, and illness manifestations were examined in a cohort with acute viral and bacterial infections (nâ =â 484). Genotyping of 12 P2RX7 function-modifying single-nucleotide polymorphisms (SNPs) was used to identify haplotypes and diplotypes. Leucocyte pore activity was measured by uptake of the fluorescent dye, YO-PRO-1, and by ATP-induced interleukin-1ß (IL-1ß) release. Associations were sought with scores describing the symptom domains, or endophenotypes, derived from principal components analysis.RESULTS:
Among the 12 SNPs, a 4-SNP haplotype block with 5 variants was found in 99.5% of the subjects. These haplotypes and diplotypes were closely associated with variations in pore activity and IL-1ß production. Homozygous diplotypes were associated with overall illness severity as well as fatigue, pain, and mood disturbances.CONCLUSIONS:
P2RX7 signaling plays a significant role in the acute sickness response to infection, likely acting in both the immune system and the brain.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções Bacterianas
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Viroses
/
Inflamassomos
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Receptores Purinérgicos P2X7
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Humans
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Middle aged
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article