Oral Presentation 12th Australasian Virology Society Meeting 2024

Natural killer cells in children with obesity have a ‘trained’ immune phenotype and heightened pro-inflammatory responses to ex vivo influenza A virus stimulation (#114)

Ellesandra C Noye 1 , Danielle Longmore 2 , Christoph Saner 2 3 4 , Meg Kaegi 2 , Julian Sng 1 , Isabelle Hocking 1 , Melanie Wu 1 , Georgina McCallum 1 , David Burgner 2 5 6 , Siroon Bekkering 2 7 , Kirsty R Short 1 8
  1. School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia
  2. Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Victoria, Australia
  3. Division of Paediatric Endocrinology, Diabetology and Metabolism, Department of Pediatrics, University Children`s Hospital Bern, Bern, Switzerland
  4. Department of Biomedical Research, University of Bern, Bern, Switzerland
  5. Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
  6. Department of Paediatrics, Monash University, Melbourne, Australia
  7. Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands
  8. Australian Infectious Diseases Research Centre, Brisbane, Queensland, Australia

INTRODUCTION: In adults, obesity increases the severity of influenza A virus (IAV) infection, but there is limited understanding of the impact of pediatric obesity on analogous outcomes. Natural Killer (NK) cells are key to innate immune responses to IAV and clearance of IAV-infected cells. ‘Trained immunity’ of NK cells and other immune cells represents a heightened immune response upon restimulation and may result in hyperinflammatory responses and subsequent pathology. Trained immunity occurs in adults and children with obesity and may contribute to worse outcomes from IAV infection, although there are no pediatric data. We aimed to investigate the NK cell responses to IAV in children with and without obesity. 

 

METHODS AND RESULTS: The phenotype of NK cells from pre-pubertal and post-pubertal individuals with/without obesity was assessed using flow cytometry. Peripheral blood mononuclear cells (PBMCs) from these individuals were stimulated with HKx31 (H3N2), Auckland/09 (H1N1) or viral mimetic R848. Cytokine response of NK cells was assessed by intracellular cytokine staining. NK cells from children with obesity have a hyperinflammatory ‘trained’ phenotype, with increased percentage of TLR4, HLA-DR, CD11c and CD11b expression relative to children without obesity. Furthermore, we demonstrate that NK cells from pre-pubertal, but not post-pubertal, children with obesity have a heightened IFN-γ response to stimulation with HKx31, Auckland/09 and R848 ex vivo.

 

CONCLUSION: We provide the first evidence that pediatric obesity induces a trained immune phenotype in NK cells, with increased cytokine responses to IAV stimulation ex vivo. Better understanding of bodyweight-related immune modulation is critical for risk-stratification, targeted prevention, development of new therapeutic strategies, and improving preparedness for the next viral pandemic.