An Inverse Relationship Between c-Kit/CD117 and mTOR Confers NK Cell Dysregulation Late After Severe Injury.

Frontiers in Immunology
Björn BöskenStefanie B Flohé

Abstract

Major trauma-induced tissue injury causes a dysregulation of the immune system. Severe systemic inflammation occurs early after the insult. Later on, an enhanced risk for life-threatening opportunistic infections develops that culminates at the end of the first week after trauma. CD56bright Natural killer (NK) cells play a key role in the defense against infection due to their rapid release of Interferon (IFN) γ in response to Interleukin (IL) 12. NK cells are impaired in IFN-γ synthesis after severe injury due to a disturbed IL-12/IFN-γ axis. Thereby, a circulating factor mediates extrinsic suppression of NK cells. Yet unknown cell-intrinsic mechanisms manifest by day 8 after trauma and render NK cells unresponsive to stimulatory cytokines. In the present study, we investigated the origin of such late NK cell-intrinsic suppression after major trauma. Peripheral blood mononuclear cells (PBMC) were isolated from patients 8 day after severe injury and from healthy control subjects and were stimulated with inactivated Staphylococcus aureus. The expression of diverse cytokine receptors, intracellular signaling molecules, and the secretion of IFN-γ by CD56bright NK cells were examined. After stimulation with S. aureus, NK cells from...Continue Reading

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Citations

May 22, 2021·International Immunopharmacology·Salvatore ChirumboloSergio Pandolfi

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Methods Mentioned

BETA
density gradient centrifugation
FACS
FCS
flow cytometry

Software Mentioned

NovoExpress
GraphPad
GraphPad Prism

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