Prolonged pro-inflammatory T cell phenotypes, increased monocyte and macrophage activity following paediatric burn injury

Donna Langley^1,2,3, Kate Zimmermann^1,2, Tony Kenna^1,2, Giorgio Steffanutti⁴, Roy Kimble⁴, Andrew Holland⁵, Mark Fear⁶, Fiona Wood⁷, Leila Cuttle^1,3,
¹School of Biomedical Sciences, Faculty of Health, Queensland University of Technology (QUT), Centre for Children’s Health Research,, South Brisbane, QLD, Australia
²Centre for Immunology and Infection Control (CIIC), QIMR Berghofer Medical Research Institute, Queensland University of Technology (QUT), Brisbane, QLD, Australia
³Centre for Biomedical Technology (CBT), Queensland University of Technology (QUT), Kelvin Grove, QLD, Australia
⁴Department of Paediatric Surgery, Urology, Burns and Trauma, Children’s Health Queensland, Queensland Children’s Hospital, South Brisbane, QLD, Australia
⁵The Children’s Hospital at Westmead Burns Unit, Kids Research Institute, Department of Paediatrics and Child Health, Sydney Medical School, The University of Sydney, New South Wales, NSW, Australia
⁶Burn Injury Research Unit, School of Biomedical Sciences, The University of Western Australia, Perth, WA, Australia
⁷Burns Service of Western Australia, Perth Children’s Hospital and Fiona Stanley Hospital, Perth, WA, Australia

Abstract

The trajectory of immune cells and mediators within the first year of a burn are unknown and may be critical for restoring homeostasis after a burn injury. The aim of this study is to characterise the dynamic immune profile for paediatric burn patients over 18 months post-burn. Flow cytometry was used to measure 26 cell markers, chemokines and cytokines reflecting both pro-inflammatory and anti-inflammatory immune profiles. The cells from 6 paediatric burn patients who had returned for repeated burn and scar treatments over 4+ timepoints within 12 months were compared to 4 healthy controls. Burn patients showed increased and unremitting pro-inflammatory cell profiles and chemotactic activity. While the level of basic immune cells such as: CD3+, CD4+, and CD8+ remained relatively constant, over time the cells had differentiated into proinflammatory cell phenotypes including Th17 and TCRγδ. There was a reduction of T-helper 1 type populations producing cytokine (TNFα), and a 3-6 fold increase of IL-17 production in the first 6 weeks. The abundance of NK and NKT-like cells was peripherally reduced for up to 6 weeks. T-regulatory cell plasticity was also observed – the Treg phenotype changes were peripherally reduced skin homing T-regs (CCR4+), increased inflammatory (CCR6+) from 1 month onward, to double positive cell types (CCR4+CCR6+) elevated for 12 months. Myeloid cell activation increased for 6 weeks, and alternatively activated macrophages displayed a 4-6 fold change compared with control. Overall these results indicate immune cells do not increase or decrease over time post-burn, but they become highly specialised, inflammatory and skin homing. These changes persist for 18 months post-burn, and this “immune distraction” would limit the ability of immune cells to prioritise other threats, such as infections, post-burn.

Biography

Donna Langley is a researcher and PhD candidate with the QUT burns and trauma research group in Brisbane. Her research is centred on the immune response to a burn, to assess metabolites through mass spectrometry, and examining immune cells through the use of flow cytometry.