Abstract
NK cells support host survival and release IL-10 following polymicrobial sepsis
The Journal of immunology (1950), Vol.204(1_Supplement), pp.148-148.21
05/01/2020
DOI: 10.4049/jimmunol.204.Supp.148.21
Abstract
Abstract The sepsis-induced cytokine storm, composed of both pro- and anti-inflammatory cytokines, leads to significant morbidity/mortality. However, the contrasting relationship between the biphasic cytokine storm components remains elusive. NK cells, whose pro-inflammatory IFNγ producing capability is well established, can also prevent immunopathology during systemic infection through anti-inflammatory IL-10 production. This bipolarity of NK cells positions them as a potential throughline for the biphasic components of sepsis. Thus, to precisely delineate the role of NK cells in sepsis utilizing a cecal ligation and puncture (CLP) model we observed diminished survival in NK-depleted mice, attributable to a prolonged cytokine storm. Notably, an increase in IL-15 was observed in NK-depleted mice suggesting that NK cells consume IL-15 during the cytokine storm. To interrogate the potential effect of IL-15, NK cells were treated in culture and with time switched from IFNγ production to IL-10 production. Further, NK cells were shown to have IL-15-dependent IL-10 production during sepsis and that IL-10 deficiency increased sepsis mortality. Importantly, we also observed elevated IL-10 production by NK cells from septic patients relative to healthy controls. Intriguingly, patients with the highest degree of sepsis-induced lymphopenia also had the greatest proportion of NK cell IL-10 production potentially indicating a relationship between the severity of sepsis and the need to counterbalance septic inflammation. These data demonstrate that NK cells limit sepsis-induced immunopathology by producing IL-10 in response to IL-15 during the cytokine storm and suggests a crucial role in balancing the biphasic components of sepsis.
Details
- Title: Subtitle
- NK cells support host survival and release IL-10 following polymicrobial sepsis
- Creators
- Isaac J JensenPatrick W McGonagillNoah S ButlerThomas S GriffithVladimir P Badovinac
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.204(1_Supplement), pp.148-148.21
- DOI
- 10.4049/jimmunol.204.Supp.148.21
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 05/01/2020
- Academic Unit
- Surgery; Microbiology and Immunology; Pathology; Molecular Physiology and Biophysics
- Record Identifier
- 9984354393402771
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