Dysregulated T helper type 1 (Th1) and Th17 responses in elderly hospitalised patients with infection and sepsis
Autoři:
John D. Coakley aff001; Eamon P. Breen aff002; Ana Moreno-Olivera aff003; Alhanouf I. Al-Harbi aff003; Ashanty M. Melo aff003; Brian O’Connell aff004; Ross McManus aff005; Derek G. Doherty aff003; Thomas Ryan aff001
Působiště autorů:
Department of Intensive Care Medicine, St James’s Hospital, Dublin, Ireland
aff001; Trinity Translational Medicine Institute, St James’s Hospital, Dublin, Ireland
aff002; Department of Immunology, Trinity Translational Medicine Institute, Dublin, Ireland
aff003; Department of Clinical Microbiology, St James’s Hospital, Dublin, Ireland
aff004; Department of Clinical Medicine and Genetics, Trinity Translational Medicine Institute, Dublin, Ireland
aff005
Vyšlo v časopise:
PLoS ONE 14(10)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0224276
Souhrn
Objective
The role of Th1 and Th17 lymphocyte responses in human infection and sepsis of elderly patients has yet to be clarified.
Design
A prospective observational study of patients with sepsis, infection only and healthy controls.
Setting
The acute medical wards and intensive care units in a 1000 bed university hospital.
Patients
32 patients with sepsis, 20 patients with infection, and 20 healthy controls. Patients and controls were older than 65 years of age. Patients with recognised underlying immune compromise were excluded.
Methods
Phenotype, differentiation status and cytokine production by T lymphocytes were determined by flow cytometry.
Measurements
The differentiation states of circulating CD3+, CD4+, and CD8+ T cells were characterised as naive (CD45RA+, CD197+), central memory (CD45RA-, CD197+), effector memory (CD45RA-, CD197-), or terminally differentated (CD45RA+, CD197-). Expression of IL-12 and IL-23 receptors, and the transcription factors T-bet and RORγt, was analysed in circulating T lymphocytes. Expression of interferon- γ and IL-17A were analysed following stimulation in vitro.
Results
CD4+ T cells from patients with infection predominantly expressed effector-memory or terminally differentiated phenotypes but CD4+ T cells from patients with severe sepsis predominantly expressed naive phenotypes (p<0.0001). CD4+ T cells expressing IL-23 receptor were lower in patients with sepsis compared to patients with infection alone (p = 0.007). RORγt expression by CD4+ T cells was less frequent in patients with sepsis (p<0.001), whereas T-bet expressing CD8+ T cells that do not express RORγt was lower in the sepsis patients.
HLA-DR expression by monocytes was lower in patients with sepsis. In septic patients fewer monocytes expressed IL-23.
Conclusion
Persistent failure of T cell activation was observed in patients with sepsis. Sepsis was associated with attenuated CD8+Th1 and CD4+Th17 based lymphocyte response.
Klíčová slova:
Cell differentiation – Cytotoxic T cells – Lymphocytes – Monocytes – Respiratory infections – Sepsis – T cells – Transcription factors
Zdroje
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