Myeloid-derived suppressor cell function and epigenetic expression evolves over time after surgical sepsis.

Autor: Hollen MK; Department of Surgery, Shands Hospital, University of Florida College of Medicine, Room 6116, 1600 SW Archer Road, Gainesville, FL, 32610-0019, USA., Stortz JA; Department of Surgery, Shands Hospital, University of Florida College of Medicine, Room 6116, 1600 SW Archer Road, Gainesville, FL, 32610-0019, USA., Darden D; Department of Surgery, Shands Hospital, University of Florida College of Medicine, Room 6116, 1600 SW Archer Road, Gainesville, FL, 32610-0019, USA., Dirain ML; Department of Surgery, Shands Hospital, University of Florida College of Medicine, Room 6116, 1600 SW Archer Road, Gainesville, FL, 32610-0019, USA., Nacionales DC; Department of Surgery, Shands Hospital, University of Florida College of Medicine, Room 6116, 1600 SW Archer Road, Gainesville, FL, 32610-0019, USA., Hawkins RB; Department of Surgery, Shands Hospital, University of Florida College of Medicine, Room 6116, 1600 SW Archer Road, Gainesville, FL, 32610-0019, USA., Cox MC; Department of Surgery, Shands Hospital, University of Florida College of Medicine, Room 6116, 1600 SW Archer Road, Gainesville, FL, 32610-0019, USA., Lopez MC; Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL, USA., Rincon JC; Department of Surgery, Shands Hospital, University of Florida College of Medicine, Room 6116, 1600 SW Archer Road, Gainesville, FL, 32610-0019, USA., Ungaro R; Department of Surgery, Shands Hospital, University of Florida College of Medicine, Room 6116, 1600 SW Archer Road, Gainesville, FL, 32610-0019, USA., Wang Z; Department of Biostatistics, University of Florida College of Medicine, Gainesville, FL, USA., Wu Q; Department of Surgery, Shands Hospital, University of Florida College of Medicine, Room 6116, 1600 SW Archer Road, Gainesville, FL, 32610-0019, USA., Brumback B; Department of Biostatistics, University of Florida College of Medicine, Gainesville, FL, USA., Gauthier ML; Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, FL, USA., Kladde M; Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, FL, USA., Leeuwenburgh C; Department of Aging and Geriatric Research, University of Florida College of Medicine, Gainesville, FL, USA., Segal M; Department of Medicine, University of Florida College of Medicine, Gainesville, FL, USA., Bihorac A; Department of Medicine, University of Florida College of Medicine, Gainesville, FL, USA., Brakenridge S; Department of Surgery, Shands Hospital, University of Florida College of Medicine, Room 6116, 1600 SW Archer Road, Gainesville, FL, 32610-0019, USA., Moore FA; Department of Surgery, Shands Hospital, University of Florida College of Medicine, Room 6116, 1600 SW Archer Road, Gainesville, FL, 32610-0019, USA., Baker HV; Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL, USA., Mohr AM; Department of Surgery, Shands Hospital, University of Florida College of Medicine, Room 6116, 1600 SW Archer Road, Gainesville, FL, 32610-0019, USA., Moldawer LL; Department of Surgery, Shands Hospital, University of Florida College of Medicine, Room 6116, 1600 SW Archer Road, Gainesville, FL, 32610-0019, USA., Efron PA; Department of Surgery, Shands Hospital, University of Florida College of Medicine, Room 6116, 1600 SW Archer Road, Gainesville, FL, 32610-0019, USA. philip.efron@surgery.ufl.edu.
Jazyk: angličtina
Zdroj: Critical care (London, England) [Crit Care] 2019 Nov 13; Vol. 23 (1), pp. 355. Date of Electronic Publication: 2019 Nov 13.
DOI: 10.1186/s13054-019-2628-x
Abstrakt: Background: Sepsis is an increasingly significant challenge throughout the world as one of the major causes of patient morbidity and mortality. Central to the host immunologic response to sepsis is the increase in circulating myeloid-derived suppressor cells (MDSCs), which have been demonstrated to be present and independently associated with poor long-term clinical outcomes. MDSCs are plastic cells and potentially modifiable, particularly through epigenetic interventions. The objective of this study was to determine how the suppressive phenotype of MDSCs evolves after sepsis in surgical ICU patients, as well as to identify epigenetic differences in MDSCs that may explain these changes.
Methods: Circulating MDSCs from 267 survivors of surgical sepsis were phenotyped at various intervals over 6 weeks, and highly enriched MDSCs from 23 of these samples were co-cultured with CD3/CD28-stimulated autologous T cells. microRNA expression from enriched MDSCs was also identified.
Results: We observed that MDSC numbers remain significantly elevated in hospitalized sepsis survivors for at least 6 weeks after their infection. However, only MDSCs obtained at and beyond 14 days post-sepsis significantly suppressed T lymphocyte proliferation and IL-2 production. These same MDSCs displayed unique epigenetic (miRNA) expression patterns compared to earlier time points.
Conclusions: We conclude that in sepsis survivors, immature myeloid cell numbers are increased but the immune suppressive function specific to MDSCs develops over time, and this is associated with a specific epigenome. These findings may explain the chronic and persistent immune suppression seen in these subjects.
Databáze: MEDLINE
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