Blood immune profiles reveal a CXCR3/CCR5 axis of dysregulation in early sepsis

Sepsis is defined as a systemic inflammatory host response syndrome after serious microbial infection, which requires prompt treatment to lower the risk of complications and death. However, early sepsis recognition can be a challenge at presentation when patients show symptoms difficult to distinguish from other acute conditions.

We designed a pilot study to explore whether blood immune signatures could reveal early specific indicator profiles for patients meeting sepsis criteria upon admission at the hospital Emergency Department. We analysed blood samples from study-recruited sepsis-suspected patients (N=20) and of age-spanning healthy volunteers (N=12), using flow cytometry-based assays. 25 circulating inflammatory cytokines and chemokines (CCs) were measured from blood plasma, while freshly isolated unfixed blood leukocytes were immunophenotyped to ascertain major cell subsets representation and expression of activation markers, including chemokine receptors. We found that beside IL-6 and sCD14, blood levels of CXCL9 and CXCL10 (two ligands of CXCR3) show good separation between healthy controls and sepsis-suspected patients. The abundance of CD4 ⁺ T cells was significantly reduced while the expression of chemokine receptors was altered on monocytes, B and all T cells from patients. In particular, we report substantial losses of CCR5-expressing monocytes and CXCR3/CCR5 double positive T cells. Full dataset analysis and post-hoc subgrouping of patients according to their diagnosis on discharge (confirmed or unconfirmed sepsis), identified CXCR3/CCR5 double expression on T cells as a separating characteristic within the study. Overall, our observational study suggests a new CCR5 and CXCL9-10/CXCR3 axis of dysregulation in early sepsis.