Investigating the link between burn injury, immune dysfunction and secondary disease

Dr Lucy Barrett1,2,3, Dr Vanessa Fear2, Dr Jason Waithman2, Professor Fiona Wood1,3,4, Dr Mark  Fear1,3

1Burn Injury Research Unit, University Of Western Australia, Nedlands, Australia, 2Telethon Kids Institute, Nedlands, Australia, 3Fiona Wood Foundation, Murdoch, Australia, 4Burns Service of Western Australia, Nedlands, Australia

Abstract:

Burn patients have a reduced life expectancy and are at increased risk of infections, cancer, and other diseases long after discharge from hospital for the burn injury itself. Of particular concern, these risks are also associated with non-severe burn injuries so understanding the mechanisms behind this is a priority. Evidence suggests that burn induces sustained immune system dysfunction, and we hypothesise this is the cause of increased prevalence of chronic disease commonly observed in burn patients.

Using mouse models of burn injury, we have demonstrated that mice subjected to a non-severe (8% total body surface area), full-thickness burn injury one month earlier were significantly more susceptible to tumour development than controls in an orthotopic model of B16 melanoma. Considering CD8+ T cells are important drivers of effective tumour suppression in this model, we investigated potential dysregulation of this immune population using mouse models of burn injury in combination with Herpes Simplex Virus infection and demonstrated that CD8+T cell expansion, differentiation and memory formation is significantly impaired following burn injury.

In paediatric patients, analysis of blood samples taken >3 years post-injury shows burn patients have reduced or absent responses to vaccine antigens (Diptheria, Tetanus, Pertussis) despite receiving their DTaP vaccine >1 year after injury. By expanding this study and performing in-depth analysis of circulating immune cells and metabolic profiles before and after vaccination, we hope to develop a strategy to identify at-risk patients and gain a greater understanding of burn-associated immune dysfunction to improve long-term outcomes for children with burns.


Biography:

Dr Barrett is a postdoctoral researcher interested in the long-term effects of non-severe burn injury on patient health and wellbeing.

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