T cells from patients with Candida sepsis display a suppressive immunophenotype

Andrej Spec, Yuichiro Shindo, Carey Ann D. Burnham, Strother Wilson, Enyo A. Ablordeppey, Evan R. Beiter, Katherine Chang, Anne M. Drewry, Richard S. Hotchkiss

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Background: Despite appropriate therapy, Candida bloodstream infections are associated with a mortality rate of approximately 40 %. In animal models, impaired immunity due to T cell exhaustion has been implicated in fungal sepsis mortality. The purpose of this study was to determine potential mechanisms of fungal-induced immunosuppression via immunophenotyping of circulating T lymphocytes from patients with microbiologically documented Candida bloodstream infections. Methods: Patients with blood cultures positive for any Candida species were studied. Non-septic critically ill patients with no evidence of bacterial or fungal infection were controls. T cells were analyzed via flow cytometry for cellular activation and for expression of positive and negative co-stimulatory molecules. Both the percentages of cells expressing particular immunophenotypic markers as well as the geometric mean fluorescence intensity (GMFI), a measure of expression of the number of receptors or ligands per cell, were quantitated. Results: Twenty-seven patients with Candida bloodstream infections and 16 control patients were studied. Compared to control patients, CD8 T cells from patients with Candidemia had evidence of cellular activation as indicated by increased CD69 expression while CD4 T cells had decreased expression of the major positive co-stimulatory molecule CD28. CD4 and CD8 T cells from patients with Candidemia expressed markers typical of T cell exhaustion as indicated by either increased percentages of or increased MFI for programmed cell death 1 (PD-1) or its ligand (PD-L1). Conclusions: Circulating immune effector cells from patients with Candidemia display an immunophenotype consistent with immunosuppression as evidenced by T cell exhaustion and concomitant downregulation of positive co-stimulatory molecules. These findings may help explain why patients with fungal sepsis have a high mortality despite appropriate antifungal therapy. Development of immunoadjuvants that reverse T cell exhaustion and boost host immunity may offer one way to improve outcome in this highly lethal disorder.

Original languageEnglish
Article number15
JournalCritical Care
Volume20
Issue number1
DOIs
StatePublished - Jan 20 2016

Keywords

  • Bloodstream infection
  • Candida
  • Fungal infection
  • Immunology
  • Sepsis
  • Shock

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