Title |
T cells from patients with Candida sepsis display a suppressive immunophenotype
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Published in |
Critical Care, January 2016
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DOI | 10.1186/s13054-016-1182-z |
Pubmed ID | |
Authors |
Andrej Spec, Yuichiro Shindo, Carey-Ann D. Burnham, Strother Wilson, Enyo A. Ablordeppey, Evan R. Beiter, Katherine Chang, Anne M. Drewry, Richard S. Hotchkiss |
Abstract |
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. 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. 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). 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 2 | 20% |
Spain | 1 | 10% |
Portugal | 1 | 10% |
Saudi Arabia | 1 | 10% |
Mexico | 1 | 10% |
United Kingdom | 1 | 10% |
Unknown | 3 | 30% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 6 | 60% |
Science communicators (journalists, bloggers, editors) | 2 | 20% |
Scientists | 1 | 10% |
Practitioners (doctors, other healthcare professionals) | 1 | 10% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 72 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 13 | 18% |
Student > Bachelor | 9 | 13% |
Student > Master | 9 | 13% |
Other | 6 | 8% |
Student > Ph. D. Student | 5 | 7% |
Other | 5 | 7% |
Unknown | 25 | 35% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 22 | 31% |
Immunology and Microbiology | 8 | 11% |
Agricultural and Biological Sciences | 6 | 8% |
Biochemistry, Genetics and Molecular Biology | 3 | 4% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 3% |
Other | 5 | 7% |
Unknown | 26 | 36% |