Blood immune profiles reveal a CXCR3/CCR5 axis of dysregulation in early sepsis.
David KealyJulie WilsonTom JaconelliKaren G HoggRebecca CoopGreg ForshawNeil ToddDavid YatesNathalie SignoretPublished in: Journal of leukocyte biology (2024)
We report on a pilot study exploring whether blood immune signatures can reveal early specific indicator profiles for patients meeting sepsis criteria upon hospital admission. We analysed samples of sepsis-suspected patients (N=20) and age-spanning healthy controls (N=12), using flow cytometry-based assays. We measured inflammatory markers from plasma fractions, and immunophenotyped freshly isolated unfixed PBMCs for leukocytes subsets representation and expression of activation markers, including chemokine receptors. We found that beside IL-6 and sCD14, CXCR3 ligands (CXCL9 and CXCL10) separated sepsis-suspected patients from healthy controls. The abundance of CD4+ T cells was significantly reduced in patients, while they displayed substantial losses of CCR5-expressing monocytes and CXCR3/CCR5 double positive T cells. Post-hoc subgrouping of patients according to their sepsis diagnosis on discharge, identified CXCR3/CCR5 double expression on T cells as a separating characteristic for confirmed cases. This work suggests a potential novel axis of dysregulation affecting CXCR3 and CCR5 in early sepsis.
Keyphrases
- end stage renal disease
- chronic kidney disease
- ejection fraction
- intensive care unit
- newly diagnosed
- acute kidney injury
- prognostic factors
- emergency department
- peritoneal dialysis
- regulatory t cells
- gene expression
- healthcare
- poor prognosis
- genome wide
- microbial community
- risk assessment
- pulmonary embolism
- dna methylation
- immune response
- patient reported outcomes
- peripheral blood
- single cell
- antibiotic resistance genes
- adverse drug